The University of Toledo
The University of Toledo Digital Repository
Theses and Dissertations
2015
The effect of blood flow restriction techniques
during aerobic exercise in healthy adults
Trent E. Cayot
University of Toledo
Follow this and additional works at: http://utdr.utoledo.edu/theses-dissertations
Recommended Citation
Cayot, Trent E., "The effect of blood flow restriction techniques during aerobic exercise in healthy adults" (2015). Theses and
Dissertations. 1884.
http://utdr.utoledo.edu/theses-dissertations/1884
This Dissertation is brought to you for free and open access by The University of Toledo Digital Repository. It has been accepted for inclusion in Theses
and Dissertations by an authorized administrator of The University of Toledo Digital Repository. For more information, please see the repository's
About page.
A Dissertation
Entitled
The Effect of Blood Flow Restriction Techniques during Aerobic Exercise in Healthy
Adults
By
Trent E Cayot
Submitted to the Graduate Faculty as partial fulfillment of the requirements for
The Doctor of Philosophy Degree in Exercise Science
____________________________________________
Barry Scheuermann, Ph.D., Committee Chair
____________________________________________
Suzanne Wambold, Ph.D., RN, Committee Member
____________________________________________
Michael Tevald, Ph.D., P.T., Committee Member
____________________________________________
David Weldy, M.D., Ph.D., Committee Member
____________________________________________
Patricia Komuniecki, Ph.D., Dean
College of Graduate Studies
The University of Toledo
May 2015
An Abstract of
The Effect of Blood Flow Restriction Techniques during Aerobic Exercise in Healthy
Adults
by
Trent E Cayot
Submitted to the Graduate Faculty as partial fulfillment of the
requirements for the Doctor of Philosophy Degree in Exercise Science
The University of Toledo
May 2015
Although the importance of aerobic exercise in disease prevention and
maintenance of a healthy lifestyle has been extensively demonstrated [1-4], it was
recently reported by the American Heart Association (AHA) that approximately 30% of
the adult population within the United States does not engage in regular aerobic exercise
[2]. The most commonly reported reason why adults did not engage in regular exercise
was due to a "lack of time" within their daily routine [5, 6]. In order to best integrate
exercise into a time constrained schedule many have turned to high-intensity interval
training (HIIT) due to the advantageous training outcomes reported in a relatively short
duration (2-4 week) [7, 8]. In addition, the exercise volume is significantly reduced
(~80-90%) during HIIT sessions compared to traditional "continuous" cardiovascular
exercise sessions [8, 9] thus decreasing the time spent exercising [8]. However, the
exercise intensities used during HIIT sessions ("all-out effort" [9, 10] or near maximal
intensities [11, 12]) may become a deterrent or may not be appropriate for certain
populations. An exercise technique known as blood flow restriction (BFR) exercise may
be an acceptable alternative approach for these populations as it utilizes low exercise
iii
intensities. BFR exercise has been shown to concurrently increase muscle hypertrophy
[13, 14], muscle strength [13] and peak oxygen uptake (VO2pk) [14, 15] subsequent to
low-intensity (i.e., walking, cycling) cardiovascular training programs. The combination
of BFR (i.e., decreased exercise intensity) and interval training (i.e., decreased exercise
volume) is both intriguing and a unique alternative solution that could potentially be
applicable to a variety of populations. This alternative exercise approach (i.e., BFR
interval training) addresses many commonly cited barriers for exercise retention (i.e.,
time constrained schedules, high exercise intensities).
Therefore, the primary purpose of this dissertation was to determine the results of
a short duration (2 weeks) BFR low-intensity interval training (BFR-LIIT) program on
aerobic capacity and skeletal muscle strength (chapter 5). However, before the primary
purpose could be investigated many secondary aims needed to be examined, including i)
determining the effect of occlusion duration on the microvascular oxygenation and
neuromuscular activation during exercise (chapter 3) and ii) determining the acute
physiological responses (oxygen uptake, microvascular oxygenation, neuromuscular
activation) to BFR used in cardiovascular exercise models (constant load, chapter 4;
interval, chapter 5).
The effects of occlusion duration were examined as healthy subjects performed
isometric knee extension contractions at different sub-maximal intensities under control
(CON, no occlusion), immediate occlusion (IO) and pre occlusion (PO) conditions.
During the IO condition the occlusion pressure (130% of the resting systolic blood
pressure, 130% SBP) was applied immediately prior to exercise while the occlusion
pressure (130% SBP) was applied five minutes prior to exercise in the PO condition.
iv
Varying the occlusion duration did not affect the neuromuscular activation of the
exercising musculature (p > 0.05), although activation did significantly increase with
increasing sub-maximal exercise intensities. However, PO elicited greater microvascular
deoxygenation (deoxy-[Hb+Mb]), as assessed by near-infrared spectroscopy) compared
to CON at all exercise intensities (p < 0.05), whereas the deoxy-[Hb+Mb] was only
greater during PO compared to IO at the lowest exercise intensity tested (20% maximal
voluntary contraction, MVC). Furthermore, IO resulted in greater deoxy-[Hb+Mb]
compared to CON only at low exercise intensities (20% MVC, 40% MVC). In
conclusion, although occlusion duration did significantly affect neuromuscular activation,
BFR techniques influenced microvascular oxygenation the most during low-intensity
exercise.
Many investigations have observed an increased neuromuscular activation with
BFR resistance exercise [16-19], however, the peripheral responses (i.e., neuromuscular
activation, microvascular oxygenation) to BFR cardiovascular exercise (i.e., cycling) has
yet to be determined. Therefore, healthy subjects performed bouts of heavy (above
estimated lactate threshold, >LT) constant cycling exercise with and without BFR. No
difference in oxygen uptake (VO2) was observed (p > 0.05) despite a greater deoxy[Hb+Mb] response during the beginning and end of BFR exercise compared to control
(CON) exercise (p < 0.05). Unlike previous BFR resistance training investigations [1619], BFR cycling exercise resulted in significantly lower neuromuscular activation during
the end of exercise. Additionally each exercise condition elicited an increase in blood
lactate concentration (from 20 watt baseline cycling to immediately post-exercise),
however, plasma vascular endothelial growth factor receptor 2 was not significantly
v
affected subsequent to any exercise condition. These results may suggest that the
perturbation caused by BFR during low-intensity cycling exercise may have a greater
localized affect within the exercising muscle, similar to previous investigations [20-23].
Lastly, healthy subjects completed a short duration BFR low-intensity interval
training (BFR-LIIT) program on a cycle ergometer. The subjects performed 8-12
intervals at 40% VO2pk during six exercise sessions across two weeks. During the BFRLIIT sessions continuous bilateral occlusion was applied to the proximal thigh at an
occlusion pressure of 130% SBP. Significant increases in the estimated LT and knee
extensor strength (isometric, eccentric) were observed following BFR-LIIT. However,
no changes were detected in VO2pk and oxidative phosphorylation capacity at the level of
the mitochondria (assessed from the phase II oxygen uptake time constant).
Collectively all of the investigations suggest that the perturbation induced by BFR
techniques during cardiovascular exercise has a greater localized affect within the
exercising musculature. Furthermore, we suggest that exercise volume is more heavily
relied upon to induce significant training stimuli during BFR exercise since the exercise
intensity is reduced. This could explain the lack of increase in VO2pk (3.3%) following
BFR-LIIT as a low exercise volume (interval exercise, 2 weeks) was combined with lowintensity exercise. Therefore, the findings within this dissertation would not recommend
the use of BFR during short duration (2 weeks), low volume (interval) exercise programs
if the training objectives include significant peak cardiovascular adaptations (VO2pk).
Future investigation into an appropriate dose response of BFR low-intensity exercise and
exercise volume is required to explain previous reports of increases in VO2pk subsequent
to BFR training [14, 15]. However, rapid improvements in muscle strength and subvi
maximal aerobic capacity (estimated LT) were observed with BFR-LIIT that may have
considerable applicability to certain populations.
vii
Acknowledgements
I would like to express my sincere gratitude and appreciation to Dr. Barry
Scheuermann for all of his time, guidance and expertise during my undergraduate and
graduate years at the University of Toledo. Dr Scheuermann although you've taught me
many lessons during the past years, I will never forget the Black Swan Hypothesis and
the importance of asking a well-developed question. I would also like to thank my
dissertation committee members (Dr Suzanne Wambold, Dr Michael Tevald and Dr
David Weldy) for their time, critical analysis, discussions of the present investigations.
Mr. Jakob Lauver, I am extremely appreciative and grateful for the many hours spent
discussing research at the white board, collaborative efforts and your friendship outside
the research lab. I wish you nothing but the best with your future endeavors in a
successful career in exercise physiology and I hope to continue our collaborations in the
future.
I would like to thank the wonderful members of my family and close friends for
their continued support and encouragement during this process. Grandpa thank you for
always being such a positive influence in my life and teaching me the value of work
ethic. Lastly, I would like to thank my beautiful wife Marci for all of her patience, love
and support. I truly would not have been able to have accomplished this without you.
viii
Table of Contents
Abstract ............................................................................................................................... iiL
Acknowledgements ........................................................................................................... viii
List of Tables ...................................................................................................................... xi
List of Figures .................................................................................................................... xi i
1 Introduction ...................................................................................................................... 1
2 Literature Review............................................................................................................. 6
3 Effects of Blood Flow Restriction Duration on Muscle Activation and Microvascular
Oxygenation During Low-Volume Isometric Exercise .................................................... 20
3.1 Introduction ............................................................................................................. 20
3.2 Methods ................................................................................................................... 23
3.3 Results ..................................................................................................................... 29
3.4 Discussion ............................................................................................................... 31
3.5 Conclusion............................................................................................................... 35
4 Acute Effects of Blood Flow Restriction During Heavy Intensity Cycling Exercise.... 41
4.1 Introduction ............................................................................................................. 41
4.2 Methods ................................................................................................................... 44
4.3 Results ..................................................................................................................... 50
ix
4.4 Discussion ............................................................................................................... 52
4.5 Conclusion............................................................................................................... 57
5 Effects of Blood Flow Restriction Low Intensity Interval Training on Cardiovascular
Endurance and Maximal Strength in Healthy Adults ....................................................... 65
5.1 Introduction ............................................................................................................. 65
5.2 Methods ................................................................................................................... 67
5.3 Results ..................................................................................................................... 76
5.4 Discussion ............................................................................................................... 78
5.5 Conclusion............................................................................................................... 81
6 Conclusion ..................................................................................................................... 96
References ......................................................................................................................... 98
Appendix A ..................................................................................................................... 115
Appendix B ..................................................................................................................... 117
Appendix C ..................................................................................................................... 119
Appendix D ..................................................................................................................... 127
Appendix E ..................................................................................................................... 135
Appendix F...................................................................................................................... 143
Appendix G ..................................................................................................................... 145
x
List of Tables
4.1 Subject Demographics.................................................................................................62
4.2 Plasma VEGF-R2 Concentrations...............................................................................63
4.3 Plasma Lactate Concentrations....................................................................................64
5.1 Subject Demographics.................................................................................................94
5.2 Training Adaptations...................................................................................................95
xi
List of Figures
3-1 Vastus Lateralis RMS vs. Intensity.............................................................................37
3-2 Vastus Medialis RMS vs. Intensity.............................................................................38
3-3 Microvascular Deoxygenation vs. Intensity................................................................39
3-4 Total Hemoglobin Concentration vs. Intensity............................................................40
4-1 Vastus Lateralis RMS vs. Exercise Duration..............................................................58
4-2 Microvascular Deoxygenation vs. Exercise Duration.................................................59
4-3 Total Hemoglobin Concentration vs. Exercise Duration.............................................60
4-4 Oxygen Uptake vs. Exercise Duration........................................................................61
5-1 Peak Oxygen Uptake Training Responses...................................................................83
5-2 Estimated Lactate Threshold Training Responses.......................................................84
5-3 Phase II Oxygen Uptake Time Constant Training Responses.....................................85
5-4 Peak Concentric Strength Training Responses............................................................86
5-5 Peak Eccentric Strength Training Responses..............................................................87
5-6 Peak Isometric Strength Training Responses..............................................................88
5-7 Oxygen Uptake vs. Interval.........................................................................................89
5-8 Microvascular Deoxygenation vs. Interval..................................................................90
5-9 Total Hemoglobin Concentration vs. Interval.............................................................91
xii
5-10 Average RMS vs. Interval.........................................................................................92
5-11 Mean Rating of Perceived Exertion vs. Interval........................................................93
xii
Chapter 1
Introduction
Individuals depend on aerobic and anaerobic energy systems in order to perform
increasing amounts of physical exertion (such as activities of daily living, recreational
activities, occupational demands, sport, etc). The increasing amount of physical exertion
to perform such activities necessitates an increase in oxygen uptake (VO2) to match the
energy requirement of the exercising muscles [24]. Peak voluntary oxygen uptake
(VO2pk) has previously been shown to be an important cardiopulmonary measurement
that is often used to classify fitness levels [1], prescribe exercise intensities [1] and to
predict mortality risk [25]. Furthermore, VO2pk has been previously demonstrated to be
"trainable" as significant increases in VO2pk (~10%) have occurred subsequent to a
variety of cardiovascular exercise programs [10, 14, 26] and in addition has been
associated with increases in peak work capacity (WRpk) and time to exhaustion [27].
The American College of Sports Medicine (ACSM) recognizes this ability to train
VO2pk via cardiovascular exercise programs and therefore recommends that a healthy
adult participate in 5-7 days of moderate intensive (40%-60% VO2pk) aerobic exercise or
3 days of vigorous intensive (≥ 60%VO2pk) aerobic exercise each week [1]. The health
benefits of regular cardiovascular exercise, such as the previously mentioned ACSM
1
recommendations, include decreased risk for many chronic cardiovascular, pulmonary,
and metabolic diseases [1-4]. Although research has demonstrated the importance of
aerobic exercise in disease prevention [1-4], it was recently reported by the American
Heart Association (AHA) that approximately 30% of the adult population within the
United States does not engage in regular aerobic exercise [2]. The most common
explanation provided by adults as to why they are not able to engage in regular exercise
or physical activity is due to a "lack of time" within their daily routine [5, 6]. Also noted
in the same report issued by the AHA was the observation that 18% of girls and 10% of
boys in grades 9-12 reported leading a sedentary lifestyle by not engaging in physical
activity at least one day per week [2]. This is an alarming statistic as the increased
occurrence of a sedentary lifestyle that is often observed within the adult population is
being portrayed within the youth population of the United States. A sedentary lifestyle
has been defined as a modifiable risk factor for cardiovascular disease [1], however,
approximately one-third of all deaths within the United States are due to cardiovascular
disease [2]. These statistics are clear evidence that further scientific investigations are
necessary to i) assist in integrating regular cardiovascular exercise into a time constrained
daily routine and ii) further investigate the role of regular cardiovascular exercise in
disease prevention strategies thereby developing effective exercise prescriptions for a
wide variety of populations.
An approach to exercise programming known as high-intensity interval training
(HIIT) has gained a considerable amount of attention and has been promoted because of
the decrease in exercise volume associated with most HIIT programs. Indeed, many
HIIT programs have an exercise volume that is approximately 80-90% less than most
2
traditional “continuous” aerobic exercise programs [8, 9]. HIIT sessions include repeated
intermittent short-duration, high-intensity bouts of exercise followed by short-duration,
low-intensity exercise bouts [28]. The high-intensity exercise bouts during HIIT sessions
are typically performed at exercise intensities equivalent to an "all-out effort" [9, 10] or at
near maximal intensities [11, 12].
Rodas and colleagues demonstrated that a short-term HIIT program completed
over a two week (14 HIIT sessions) training period using “all-out” exercise intensities
significantly increased VO2pk within a healthy, recreationally active male population [10].
Furthermore, muscle biopsies obtained from the vastus lateralis indicated significant
increases in citrate synthase following the HIIT program [10]. Citrate synthase is the
enzyme responsible for catalyzing acetyl-CoA and oxaloacetate to form citrate in the first
step of the tricarboxylic acid (TCA) cycle [29] and has been used extensively as a marker
of muscle aerobic capacity, particularly following exercise training [30]. In agreement
with Rodas and colleagues [10], VO2pk and citrate synthase was shown to significantly
increase following a HIIT program in a healthy, recreationally active, female population
using near-maximal exercise intensities (90% VO2pk) and a lower exercise volume (13
days, 7 HIIT sessions) [12]. Little and colleagues [7] reported similar training
adaptations as significant elevations in citrate synthase following a short-term, lowvolume HIIT program (2 weeks, 6 HIIT sessions, 100%VO2pk) within a healthy,
recreational active male population. Citrate synthase responses subsequent to a HIIT
program have been shown to be similar to the citrate synthase response following a
traditional cardiovascular exercise program (65% VO2pk, 40-60 min per session, 5 days
per week) despite the significant differences in exercise volumes [9]. Other important
3
biomarkers (peroxisome proliferator-activated receptor γ coactivator 1 alpha, PGC-1α)
that promote mitochondrial biogenesis [31, 32] have been previously reported to be
upregulated following the completion of HIIT programs [9, 33].
Although HIIT appears to be an attractive alternative exercise option due to the
physiological improvements [27] and the reduction in exercise volume [8, 9], a portion of
the exercise session is performed at relatively high-intensities ("all-out effort"[9, 10], near
maximal [7, 11]). The high-intensity exercise could become a deterrent to an individual
due to the relatively high amount of effort required or may not be suitable for some
exercising populations. Therefore, this dissertation will investigate the implementation of
a rather unique exercise technique known as blood flow restriction (BFR) exercise during
the performance of aerobic exercise.
Previous scientific investigations have used BFR techniques combine with lowintensity exercise in order to induce metabolic stress [34-36] and mimic high-intensity
exercise in both resistance exercise models [37-43] and cardiovascular (cycling, walking)
exercise models [13-15, 44-47]. VO2pk has been previously shown to increase in healthy
young men following both cycling and walking programs that incorporated BFR [14, 15].
Not only was an increase in VO2pk observed following a BFR cycling program [14], but
muscular endurance, measured as an increase in time to task failure, and muscular
hypertrophy, as evidenced by an increase in muscle cross-sectional area, have also been
shown to increase compared to a typical low-intensity (40% VO2pk, 45 min) cycling
exercise program [14]. In addition, previous BFR investigations utilizing low-intensity
walking programs have demonstrated increases in anaerobic capacity, assessed by the
4
Wingate test [15], stroke volume [15], skeletal muscle hypertrophy [13, 44], skeletal
muscle dynamic strength [13], and skeletal muscle isometric strength [13, 44].
One possible mechanistic explanation for the aerobic training adaptations
following BFR aerobic exercise programs could be due to increases in vascular
endothelial growth factor (VEGF) concentrations. VEGF has been established as a
potent exercise-induced angiogenic stimulator [48, 49] and has been associated with the
formation of new capillaries and improvements in oxygen delivery to exercising skeletal
muscle [49-52]. The increased VEGF expression, previously observed subsequent to
BFR resistance exercise [43, 53, 54], could promote angiogenesis during a BFR
cardiovascular training program and potentially improve oxygen delivery and utilization
and thus subsequently increase VO2pk. However, to our knowledge the response of
plasma VEGF has not been previously observed following acute BFR aerobic exercise
(Chapter 4).
In addition, many methodological considerations arise regarding BFR prior to
implementing BFR techniques into an aerobic exercise program. Mainly, how does the
occlusion duration affect the local muscular environment (Chapter 3)? This is an
important consideration as the increases in metabolic stress and hypoxic intramuscular
environments have been suggested as necessary exercise stimuli during the performance
of BFR exercise [35, 36, 55]. Therefore, the primary objectives of this dissertation is to i)
determine the peripheral effects of BFR implemented into a cardiovascular exercise
model and ii) to determine the physiological training adaptations that result from BFR
low-intensity cardiovascular training programs and then compare the training outcomes
to those observed from a high-intensity cardiovascular training program.
5
Chapter 2
Literature Review
Individuals depend on aerobic and anaerobic energy systems daily in order to
perform increasing amounts of physical exertion (such as activities of daily living,
recreational activities, occupational demands, sport, etc). The increasing amount of
physical exertion to perform such activities requires an increase in pulmonary oxygen
uptake (VO2) to offset the energy requirement of the exercising muscles [24]. Peak
voluntary oxygen uptake (VO2pk) has previously been shown to be an important
cardiopulmonary measurement that is often used to classify fitness levels [1], prescribe
exercise intensities [1] and has been used to predict mortality risk [25]. VO2pk has also
been previously shown to be "trainable" as significant increases (~10% - 19%) have been
reported subsequent to a variety of cardiovascular training programs [10, 14, 26, 56]. In
addition, the increased VO2pk reported subsequent to cardiovascular training programs
has been associated with increases in peak work rate capacity (WRpk) and muscular
endurance (time to exhaustion) [8, 27, 56].
Although VO2pk is commonly used as a marker of cardiovascular training status,
other pulmonary gas exchange markers (such as estimated lactate threshold or the time
course for adjustment of VO2 following a work rate transition) can provide pertinent
6
information regarding an individual's cardiovascular training status. For instance,
changes in the lactate threshold can be estimated non-invasively during graded exercise
tests prior and subsequent to a cardiovascular training program via observing the
pulmonary gas exchange data [57, 58]. Typically, a method known as the v-slope
method is used to identify the estimated lactate threshold, which is defined as the point in
which carbon dioxide production measured at the mouth (VCO2) begins to increase
disproportionately to the rise in VO2 [57, 58]. The ventilatory equivalents (VE/VCO2,
VE/VO2) are ratios of ventilation (VE) to VCO2 and to VO2 and can also be used to help
identify the estimated lactate threshold [24].
During exercise within the heavy intensity domain (above lactate threshold, >LT)
there is an increased rate of appearance of lactatic acid (HLa) which becomes dissociated
into hydrogen ions (H+) and lactate (La-) [29]. Carbon dioxide (CO2) is one product of
the reaction when the H+ are buffered by bicarbonate (HCO3-) [24, 29]. The additional
CO2 production from the H+ buffering reaction along with the CO2 production from the
tricarboxylic acid (TCA) cycle can be observed in the VCO2 data during a graded
exercise test as a sharp, upward deflection point [24]. As VCO2 increases there will be an
increased ventilatory drive (increasing VE) and therefore the rise in VE/VO2 will continue
to increase while VE/VCO2 remains constant indicating isocapnic buffering and the
estimated lactate threshold [24].
In addition to VO2pk and the estimated lactate threshold, further information
regarding the cardiovascular training status of an individual can be obtained from
observing the time course of the VO2 response during non-steady state exercise. During
a transition from unloaded, or minimally loaded (20 watts), exercise to a work rate within
7
the moderate intensity domain (<LT) the VO2 will follow an exponential pattern,
subsequent to a time delay, prior to reaching a newly established steady state [59]. This
exponential pattern can be modeled mathematically and will display two phases during
the exercise transition within the moderate intensity domain [60]. The phase II of the
non-steady state VO2 response (fundamental phase) has been shown to predominantly
reflect the kinetic response of the muscle's oxygen utilization [60, 61]. The time constant
of the phase II VO2 response (τVO2) has been previously reported to become faster
during moderate intensity work rate transitions following both traditional cardiovascular
training programs [8, 62, 63] and high-intensity interval training (HIIT) programs [8, 56,
62]. Although rather time consuming during the data collection and data analysis
processes, determining changes in τVO2 subsequent to cardiovascular training programs
provides more confidence in the results and interpretation of any changes observed in
VO2pk. Since τVO2 can be assessed within the moderate intensity domain (<LT), the
participant does not have to provide as great of effort during the test unlike the maximal
effort required during a graded exercise test when assessing VO2pk.
These cardiovascular adaptations that can be observed within the pulmonary gas
exchange data are important indicators of the effectiveness of a cardiovascular exercise
program and an individual's ability to perform work. The guidelines set forth by the
American College of Sports Medicine (ACSM) recommends that a healthy adult
participate in 5-7 days of moderate intense (40%-60% VO2pk) cardiovascular exercise or
3 days of vigorous intense (≥ 60%VO2pk) cardiovascular exercise each week [1]. The
health benefits of regular cardiovascular exercise, such as the previously mentioned
ACSM recommendations, include decreased risk for many chronic cardiovascular,
8
pulmonary, and metabolic diseases [1-4]. Although research has demonstrated the
importance of aerobic exercise in disease prevention [1-4], it was recently reported by the
American Heart Association (AHA) that approximately 30% of the adult population
within the United States did not engage in regular cardiovascular exercise [2]. The most
commonly reported explanation provided by adults as to why they are not able to engage
in regular cardiovascular exercise was due to a "lack of time" within their daily routine
[5, 6]. Also shockingly noted in the same report issued by the AHA, 18% of girls and
10% of boys (grades 9-12) reported leading sedentary lifestyles by not engaging in
physical activity at least one day per week [2]. This is a mortifying statistic as the
increased occurrence of sedentary lifestyles often observed within the adult population is
also being portrayed within the youth population of the United States. Although the trend
for sedentary lifestyles seem to be high in both the youth and adult populations, sedentary
lifestyles have been defined as a modifiable risk factor for cardiovascular disease [1].
Therefore it could be suggested that further scientific investigations on the best approach
to integrate exercise into a time constrained daily routine and the effectiveness of the
exercise programs are of vital importance. Therefore, the primary objectives of this
dissertation is to 1) determine the systemic effects of an alternative exercise (blood flow
restriction, BFR) technique implemented into a cardiovascular exercise model and 2) to
compare the physiological training adaptations from a BFR low-intensity cardiovascular
training program to the training outcomes from a high-intensity cardiovascular training
program.
High-Intensity Interval Training (HIIT) Programs
9
High-intensity interval training (HIIT) programs have gained much attention
within the exercise science field due to the advantageous cardiovascular training
adaptations that have been demonstrated to occur within a relatively short amount of time
(2 - 6 weeks) [7, 9, 64]. HIIT sessions include repeated intermittent high-intensity
exercise bouts followed by low intensity exercise bouts [28]. The portions of the HIIT
exercise sessions that are performed at high intensities equate to an "all-out effort" [9]
and/or near-maximal (≥90% VO2pk ) [7, 65] efforts. The performance of the high
intensity exercise allows some HIIT exercise programs to reduce exercise training
volume by up to 80-90% compared to traditional continuous endurance training programs
[8, 9]. The drastic reduction in exercise volume, allowing for a relatively low time
commitment, and rapid physiological adaptations makes HIIT programs an attractive
alternative exercise option for many.
Short-Term High-Intensity Interval Training (HIIT) Responses
Previous literature has suggested that HIIT improves VO2pk in both healthy [9, 10,
66] and clinical (i.e., cardiovascular disease, CVD) populations [67-69]. Previously, a
HIIT (95% VO2pk) program was shown to significantly increase VO2pk to a greater extent
compared to traditional, continuous, moderate intensity (50% VO2pk) cardiovascular
training, even though the moderate intensity program did significantly increase VO2pk
compared to pre-training levels [70]. However, similar changes in VO2pk have been
reported following HIIT and continuous (65% VO2pk) cardiovascular training programs
[8] as well as no change in VO2pk subsequent to a HIIT program [64, 71]. Furthermore,
increases in citrate synthase (CS) and peroxisome proliferator-activated receptor gamma
coactivator 1α (PGC-1α) have been shown following both traditional, continuous
10
cardiovascular training (5 days/week, 6 weeks, ~2250 kJ/week) as well as HIIT (3
days/week, 6 weeks, ~250 kJ/week) in a young, healthy population [9]. CS is the enzyme
responsible for catalyzing acetyl-CoA and oxaloacetate to citrate in the first step of the
TCA cycle [29] while PGC-1α has been associated with the promotion of mitochondrial
biogenesis [31, 32]. Despite the increased values from the pre-training levels, similar
training adaptations occurred subsequent to both cardiovascular training programs (HIIT,
continuous) as there was no difference in CS or PGC-1α between the groups during the
post-training analysis [9]. In addition, a short-term (2 week), low-volume HIIT program
demonstrated increases in CS, phosphocreatine, and creatine kinase activity subsequent to
training [10]. The increased CS reported following HIIT [9, 10] may provide a faster
transition for oxidative phosphorylation in order to match the energy requirement
imposed by the exercising muscles. This could also be supported by the previously
observed speeding of the τVO2 during phase II of a moderate intensity transition
following a HIIT program [8, 56]. The culmination of the previous results could suggest
that HIIT can help to improve the individual's aerobic capacity, capacity for oxidative
phosphoralation [29] and initiate mitochondrial biogenesis [31].
The effect that a HIIT program had upon the oxygenation status of the
microvasculature during an incremental fatigue protocol had been previously observed
[72]. The authors reported that after six weeks of an HIIT program significant increases
in microvascular deoxygenation ([HHb]) during an incremental fatigue protocol was
observed [72]. According to the interpretation of the authors, the increased [HHb]
subsequent to the HIIT program suggested an improvement in oxygen extraction from the
muscle [72]. According to Fick's equation (VO2 = CO x a-VO2diff), if the participants
11
ability to extraction oxygen (i.e., a-VO2diff) were to increase following training, peak
oxygen consumption (VO2pk) may be elevated as well. However, no significant
difference in [HHb] kinetics were detected during moderate intensity work rate
transitions following a HIIT program [8, 56] or a continuous, cardiovascular training
program [8]. The [HHb] kinetics have been suggested to reflect the rate of oxygen
extraction within the microvasculature [8, 56]. Interestingly, the authors observed a
faster response in τVO2 during phase II of a moderate intensity transition after just two
exercise sessions for each of the exercising conditioning (HIIT, continuous) [8]. The
authors' conclusion was that during each mode of aerobic exercise that was examined
(HIIT, continuous) an increase in muscle oxygen utilization was observed with no
changes observed in the rate of oxygen extraction, thus resulting in a matching of oxygen
utilization and blood flow following training [8]. These findings [8, 72] help to provide
mechanistic evidence to the effect and time course of the training adaptations observed
subsequent to HIIT exercise programs [9, 10, 66]. However, further investigation is
required to explain how other alternative modes of cardiovascular exercise (i.e., BFR)
may influence these training adaptations.
Acute Physiological Responses of High-Intensity Interval Training (HIIT) Sessions
Participants performing a single HIIT exercise session (6 intervals, 30 seconds allout intensity, 2 minutes active recovery) has been shown to achieve ≥ 90% VO2pk and
high levels of blood lactate concentration (15.3 ± 0.7 mmol/L) [65]. The authors attribute
these physiological responses to be possible precursors for the training adaptations
associated with HIIT exercise [28, 65]. The increase in blood lactate concentration (i.e.,
high metabolic stress) observed during HIIT exercise [65, 73] have been suggested to be
12
a possible precursor for an elevated expression of vascular endothelial growth factor
(VEGF) mRNA [54]. Vascular endothelial growth factor (VEGF) has been established
as a potent exercise-induced angiogenic stimulator [48, 49] and has been associated with
the formation of new capillaries and improvements in oxygen delivery to exercising
skeletal muscle [49-52]. However, the acute effects that HIIT has upon the
microvascular oxygenation and neuromuscular activation of the exercising muscle remain
to be investigated.
Although HIIT appears as an attractive exercise program due to the reduction in
the total exercise volume (i.e., time commitment) and rapid cardiovascular adaptations,
the use of high exercise intensities becomes a concern due to the high amounts of effort
required by the participants to complete the training program. It would be of interest to
investigate the implementation of an alternative exercise technique (i.e., BFR) that could
reduce the exercising intensity and determine if significant cardiovascular training
adaptations will still occur subsequent to cardiovascular training.
Blood Flow Restriction (BFR) Exercise
Heavy resistance exercise, utilizing an intensity of ≥65% of an individual's one
repetition maximum (1RM) and/or maximal voluntary contraction (MVC), has
traditionally been used in progressive strength training programs to increase skeletal
muscle strength and hypertrophy [74, 75]. However, recently an alternative exercise
technique known as blood flow restriction (BFR) exercise has gained much attention as
low exercise intensities (20% - 40% 1RM/MVC) are utilized to mimic high-intensity
exercise responses. Increases in skeletal muscle cross-sectional area [13, 41], muscle
strength [13, 17, 40, 41], maximal rate of torque development [40], growth hormone
13
concentration [16] and muscle protein synthesis [38, 39] have been demonstrated as
training adaptations subsequent to BFR low-intensity resistance exercise.
Blood Flow Restriction (BFR) Cardiovascular Training Responses
In addition to the muscle hypertrophy and strength improvements associated with
BFR resistance training, BFR techniques have been previously incorporated into lowintensity cardiovascular exercise (i.e., walking, cycling) models and have demonstrated
advantageous cardiovascular training adaptations subsequent to training. The
cardiovascular adaptations include increased VO2pk [14, 15, 21], muscular endurance (as
assessed by an increased time to exhaustion) [14, 20, 21], CS [20, 23], anaerobic capacity
as assessed by the Wingate test [15], stroke volume [15], skeletal muscle hypertrophy
[13, 14], bilateral dynamic strength (leg press 1RM) [13], unilateral dynamic strength
(leg curl 1RM) [13] and isometric strength [13] following training. Although these
beneficial cardiovascular adaptations have been previously reported subsequent to BFR
cardiovascular exercise programs, many questions remain to be answered regarding the
stimulus, or stimuli, responsible for the training outcomes.
Acute Physiological Responses of Blood Flow Restriction (BFR) Cardiovascular
Exercise
A potential mechanism for the increased aerobic capacity subsequent to BFR
cardiovascular exercise training programs could be due to a greater mitochondrial density
within the trained musculature. Muscle biopsy samples from the vastus lateralis after one
session of low-intensity (26 ± 4% of peak work load), unilateral knee extension exercise
demonstrated that PGC-1α was significantly greater subsequent to BFR knee extension
exercise compared to free-flow (control) exercise [22]. Once again, PGC-1α has been
14
suggested to be a vital component during exercise induced mitochondrial biogenesis
process [31].
However another potential acute response previously observed during acute BFR
exercise is an increased VEGF concentration subsequent to exercise since VEGF has
been previously reported as a potent exercise-induced angiogenic stimulator [48, 49]. It
has previously been demonstrated that increases in plasma vascular endothelial growth
factor receptor 2 (VEGF-R2) concentration occurs following acute low-intensity (20%
1RM) BFR resistance exercise (i.e., knee extension) [53]. While VEGF-R2 mRNA has
been shown to be significantly elevated within skeletal muscle (i.e., vastus lateralis)
following low-intensity (40% 1RM) BFR knee extension exercise [43] and 45 minutes of
dynamic, low-intensity knee extension exercise (24 ± 3% peak workload) combine with
BFR (50 mmHg lower body positive pressure) [54]. In addition, the authors of the
investigation demonstrated a significant, positive correlation (r = 0.54, p < 0.05) between
exercise induced VEGF mRNA expression and venous lactate concentration, thus
suggested that the VEGF mRNA expression could be related to the "metabolic stress"
accrued from exercise [54]. The observed relationship between VEGF expression and
metabolic stress (i.e., lactate concentration) during BFR exercise could potentially
explain the elevations in VEGF observed previously during BFR exercise [43, 53] as
lactate concentration was also shown to be significantly greater during low-intensity BFR
exercise compared to low-intensity control exercise [22, 53, 76] and during exercise
under hypoxic breathing conditions [77].
Another potential mechanistic link for the elevations of VEGF following BFR
exercise could be due to the increased neuromuscular activation that is associated with
15
BFR exercise compared to free-flow (control) exercise [16-19]. VEGF expression has
been demonstrated to increase significantly subsequent to increased muscle activity (i.e.,
motor nerve stimulation) within an animal model [78, 79]. Therefore, it could be
suggested that the increased neuromuscular activity observed during BFR exercise [1619] might be associated with the elevated post-exercise expressions of VEGF that has
been previously demonstrated [43, 53]. Despite the uncertainty surrounding the exact
mechanistic link for the expression of VEGF during BFR exercise, the concurrent
elevation of VEGF expression and increase in PGC-1α (i.e., mitochondrial biogenesis
precursor) observed subsequent to BFR exercise may partly be associated with the
increases in VO2pk previously reported subsequent to BFR cardiovascular training [14,
15, 21].
Although the exact mechanism(s) (i.e., hypoxic intramuscular environment [19],
metabolic byproduct accumulation [80]) explaining BFR exercise and the resulting
training adaptations are currently still under debate, some evidence suggests that the
training adaptations (i.e., increased VO2pk) following BFR cardiovascular training may
occur due to peripheral adaptations [20-23]. This has been previously hypothesized as
training adaptations have been observed in the experimental (BFR) leg subsequent to
BFR cardiovascular training while no adaptations have been observed in the contralateral,
control leg [20-23]. BFR exercise may also follow similar training principles similar to
control exercise (i.e., principle of specificity) as performance responses (VO2pk and time
to exhaustion) reported for the experimental condition (BFR) were greater during
ischemic testing conditions compared to control testing conditions subsequent to BFR
training [21]. These observations come from a series of studies that were conducted
16
using lower body positive pressure (LBPP) to provide an ischemic intramuscular
environment during exercise [20-23]. The LBPP technique has been shown to reduce
blood flow by approximately ~16% (0.3 liters per minute, L/min) during low-intensity
exercise [81], while BFR (i.e., proximal occlusion cuff, 130% SBP occlusion pressure)
techniques have been shown to reduce blood flow by approximately ~30% (~0.2 L/min)
during low-intensity exercise [53]. LBPP (50 mmHg above atmospheric pressure) lowintensity exercise has also demonstrated to significantly increase oxygen extraction (i.e.,
greater arterial-venous oxygen difference) [81] and exercising heart rate [21] compared to
control (i.e., free flow) during acute (one session) low-intensity exercise. Subsequent to
LBPP low-intensity cycling training significant increases in VO2pk [21], muscular
endurance (time to exhaustion) [21, 23] and CS [23] were reported when compared to
control low-intensity cycling training, similar training responses as BFR cardiovascular
training programs.
In conclusion, similar training adaptations have been reported following both
HIIT and BFR cardiovascular training programs which included significantly increased
CS, PGC-1α, and VEGF expression subsequent to acute exercise sessions and
improvement in VO2pk following training. However, to the author's knowledge it has yet
been determined how BFR cardiovascular training programs affect the estimated lactate
threshold and the oxidative phosphorylation capacity of the trained musculature (i.e.,
phase II τVO2 during a moderate intensity step work rate transition). Furthermore, it has
been previously suggested that BFR cardiovascular training adaptations result from
peripheral adaptations [20-23], therefore, further investigation into the acute effects of
BFR on microvascular oxygenation and neuromuscular activation of the skeletal muscle
17
could provide further evidence to suggest a potential stimulus/stimuli responsible for the
training adaptations observed following BFR cardiovascular exercise programs.
Blood Flow Restriction (BFR) Exercise Safety Considerations
The beneficial training adaptations that have been demonstrated following the use
of BFR training programs have the potential to be applied to a variety of populations (i.e.,
healthy, novice, elderly, rehabilitation, occupational, sport), however, safety of BFR
exercise is of primary importance as formation of thrombus and induced microvascular
damage has been associated with increased pressurization of blood vessels [82-85].
Therefore, previous studies have investigated potential safety concerns (i.e., blood clot
formation, microvascular inflammation, microvascular damage, neuromuscular
complications, muscle damage) that have been raised while using BFR exercise
techniques. For instance, Clark et al [86] previously demonstrated that acute (four weeks,
3 days/week) knee extension training within a young, healthy population (18-30 years
old) resulted in an increase in isometric strength (BFR = ~8%, high-intensity = ~13%)
with no difference observed in ankle-brachial index or nerve conduction (i.e., defined as
the latency response of the H-relfex) following the completion of training in either group
(BFR or high-intensity). Furthermore, no change acutely (following the first exercise
session) or chronically (following the completion of the four week training program) was
observed in prothrombin time, fibrinogen, D-dimer, and/or high sensitivity C-reactive
protein from baseline (pre-training) measurements in either group [86].
In agreement with Clark et al [86], no change in D-dimer was observed following
a BFR knee extension exercise session in young (25.1 ± 2.8 years), healthy males [87] or
in stable, older (57 ± 6 years), ischemic heart disease patients [88]. Madarame et al [88],
18
also observed no change in high sensitivity C-reactive protein following BFR knee
extension exercise in ischemic heart disease patients, a similar finding demonstrated in
young, healthy population by Clark et al [86]. The collective conclusion of the previous
investigations suggest that BFR exercise does not expose the participant to any higher
risk of blood clots or inflammation compared to high-intensity resistance training [86].
Karabulut et al [89] found no significant increase in creatine kinase and/or
interleukin 6 following six weeks of resistance training (BFR group and high-intensity
group) performed by healthy, older (56.6 ± 0.6 years) males. The authors of the previous
investigation suggest that this finding implies a lack of skeletal muscle damage and
inflammatory response following BFR exercise training. However, this conclusion
should be interpreted with caution since the post-training blood samples were collected
24 hours subsequent to the last training session and creatine kinase has been shown not to
peak until 48-96 hours post exercise [89-91]. Nevertheless, torque decrements (used as
an indirect muscle damage marker) following BFR exercise have been shown to return to
baseline measurements 24 hours after the exercise session, suggesting a lack of muscle
damage in this condition [92].
Furthermore, based upon survey results of 12,642 participants, BFR exercise has
been shown to be a safe and effective form of exercise that has been associated with only
a small number of complications reported [82]. The most common complication that has
been reported during BFR exercise has been subcutaneous hemorrhage or bruising
(~13%) of the exercising limb [82]. The results of the survey also demonstrate that BFR
exercise sessions typically last 5-30 minutes in duration and are performed on average 13 days/week [82].
19
Chapter 3
Effects of Blood Flow Restriction Duration on Muscle Activation and Microvascular
Oxygenation During Low-Volume Isometric Exercise
Cayot TE, Lauver JL, Silette CR, Scheuermann BW. (2015). Effects of blood flow
restriction duration on muscle activation and microvascular oxygenation during lowvolume isometric exercise. Clin Physiol Funct Imaging (Ahead of Print).
3.1 - Introduction
Heavy resistance exercise, utilizing an intensity of ≥65% of an individual's
maximal voluntary contraction (MVC), has typically been used in progressive strength
training programs to increase skeletal muscle strength and hypertrophy [74, 75].
However, high intensity exercise may not be well suited for use in some patient
populations and/or settings (i.e., novice exerciser, elderly, rehabilitation) thereby limiting
the potential health and performance improvements [93]. Recent studies have suggested
that utilizing blood flow restriction (BFR) techniques in combination with low-intensity
(20%-40%MVC) resistance exercise results in similar increases in skeletal muscle crosssectional area [13, 41], muscle strength [13, 17, 40, 41], maximal rate of torque
development [40], growth hormone concentration [16] and muscle protein synthesis [38,
39] compared to heavy resistance exercise (≥65% MVC). The proposed mechanisms by
which BFR resistance training is thought to work include a hypoxic intramuscular
20
environment [19], increased cellular swelling [80], and/or increased metabolic byproduct
accumulation [80].
Investigators have previously demonstrated that four weeks of low-intensity
(40%MVC) isometric BFR training significantly improved isometric muscle strength and
maximal rate of torque development [40]. However, the potential effect that isometric
BFR exercise had on neuromuscular activation, both immediately and following training,
was not previously examined in that investigation [40]. Although the underlying
mechanism(s) explaining BFR training adaptations are still a matter of debate, many
studies have shown an increase in neuromuscular activation [16-19] and firing frequency
[19] of the exercising muscles during isotonic exercise with BFR conditions compared to
free flow (i.e., non-BFR, control) conditions. Increased neuromuscular activation has
been hypothesized as a mechanism for eliciting muscular strength gains [40, 94].
Therefore, BFR exercise, which has been shown to increase neuromuscular activation
acutely during exercise with low-intensity resistance loads, could potentially provide an
alternative approach to heavy resistance training in order to promote muscular strength
gains in populations where heavy resistance exercise may not be appropriate.
In order for BFR exercise to be an effective exercise modality, the methodological
approach to BFR exercise techniques must be systematically evaluated. This includes
identifying the most effective occlusion duration, as occlusion durations have varied in
previous BFR studies and has been shown to affect cellular swelling [80] and
neuromuscular activation [16-19]. For instance, a previous investigation has indicated
that an initial restrictive pressure applied four minutes prior to the application of the
target occlusion pressure caused a significant decrease in the microvascular oxygenation
21
of the skeletal muscle during supine rest as measured via near-infrared spectroscopy
(NIRS) techniques [95]. However, this investigation [95] did not examine the potential
effect(s) that an initial restrictive pressure could have on microvascular oxygenation
and/or neuromuscular activation during exercise under BFR conditions. As previously
suggested, if decreased microvascular oxygenation provides a stimulus for altered
neuromuscular activation within the muscle [16, 96, 97], then determining the optimal
occlusion procedure would be beneficial for developing an effective and efficient BFR
exercise program.
In order to better understand how neuromuscular activation and microvascular
oxygenation is immediately affected by varied BFR occlusion durations, a low-volume
isometric exercise protocol was employed during the present investigation. The lowvolume isometric BFR exercise protocol used in the present investigation has not been
associated with an increase in muscle strength or hypertrophy and differs from the typical
high-volume, isotonic BFR exercise protocols previously reported [98, 99]. However, it
was the intent of the present study to primarily focus on the immediate effects that varied
occlusion durations had upon neuromuscular activation and microvascular oxygenationdeoxygenation while simultaneously minimizing the confounding influence of the
accumulation of metabolic byproducts that would be elicited from a higher exercise
volume. Therefore, the primary purpose of the present investigation was to examine the
effects of occlusion duration on neuromuscular activation and microvascular oxygenation
during BFR isometric knee extension exercise preformed at various sub-maximal
intensities. It was hypothesized that a longer occlusion duration would elicit an increased
neuromuscular activation at a given sub-maximal contraction intensity. It was also
22
hypothesized that a longer occlusion duration would cause a lower microvascular
oxygenation response (i.e., greater deoxygenation, deoxy-[Hb+Mb]) while
simultaneously increasing blood volume (i.e., total hemoglobin concentration, [THC])
within the microvasculature as measured using near-infrared spectroscopy.
3.2 - Methods
Healthy, recreationally active, college-aged male subjects (n = 7; age = 24.8 ± 1.4
years; height = 181.0 ± 3.0 cm; weight = 81.4 ± 0.1 kg) participated in the study. The
number of subjects included in the present investigation was determined based upon
previous BFR investigations that observed similar outcome variables [19, 95]. The
purpose, benefits, and risks associated with the study were explained to each subject.
Prior to participation each subject read and voluntarily signed an informed consent form
approved by the university's institutional research review board for human subjects,
which was in agreement with the guidelines set forth by the Deceleration of Helsinki.
Each subject completed medical health history and activity level questionnaires, which
were used for inclusion/exclusion purposes. Any individual that had been previously
diagnosed with a metabolic, pulmonary and/or cardiovascular disease (including
hypertension) and/or an orthopedic-related injury within the last 12 months was excluded
from participation in the study. Each subject was asked to refrain from participating in
any strenuous physical activity for 24 hours prior to each testing session. The testing
session was scheduled for approximately the same time of day for each subject.
Exercise Protocol
Each subject participated in four separate sessions, during which one set of four
repetitions of sub-maximal isometric knee extension were performed at 90° of knee
23
flexion for each BFR condition. The exercise intensities (20%MVC, 40%MVC,
60%MVC, 80% MVC) and BFR conditions were randomized between and within each of
the four sessions, respectively. The BFR conditions that were evaluated included control
(CON, no occlusion), immediate occlusion (IO) and pre-occlusion (PO). During the
CON condition the occlusion cuff was placed around the distal thigh but was not inflated
either before or during the exercise. The occlusion cuff was inflated immediately prior to
exercise and remained inflated during exercise for the IO condition (~110 seconds).
During the PO condition, the occlusion cuff was inflated five minutes prior to the onset of
exercise and remained inflated throughout exercise (~7 minutes). The occlusion cuff was
immediately deflated following the completion of the last repetition during both of the
BFR (IO, PO) exercise sets.
At the beginning of each session the subject was seated and remained at rest for
five minutes prior to measuring blood pressure. All blood pressure measurements were
obtained with the upper arm supported at heart level with the subject seated in an upright
position. Following the blood pressure measurement, the distance from the anterior
superior iliac spine (ASIS) to the superior border of the patella was measured and
recorded. An occlusion cuff (Hokanson, SC5, Bellevue, WA, 6.0 cm width) was
positioned at 33% of the distance distal to the ASIS on the dominant thigh, which is
similar to the cuff positioning described in a previous BFR investigation [100]. The
external occlusion pressure used during all BFR conditions was equivalent to 130% of
the subject's resting systolic blood pressure (130% SBP), consistent with the external
occlusion pressure used in previous BFR investigations [15, 36, 42, 53, 101]. Surface
electromyography (sEMG) and near-infrared spectroscopy (NIRS) techniques were used
24
to measure neuromuscular activation and microvascular oxygenation of the exercising
muscle tissue, respectively.
Following the placement of the occlusion cuff and all data collection electrodes
(see Surface Electromyography Techniques and Near-Infrared Spectroscopy Techniques
below), the subject remained seated upright in a padded chair while a padded strap was
secured around the ankle of their dominant leg. All exercise was performed on the
subject’s dominant leg [102]. The subject was secured with straps across the hips and
shoulders in order to minimize movement during the isometric exercise sets. The ankle
strap was connected to a force transducer (Omega, LCCA-1K, Stamford, CT) so that
force production could be recorded and visually displayed to the subject on a computer
monitor. The length of the ankle strap was adjusted so that the subject's knee remained at
90° of knee flexion during each isometric contraction. The force transducer was
calibrated via the manufacture's guidelines with a five point calibration curve prior to
each testing session. The subject performed two sets of eight repetitions of isometric
knee extension at self-selected intensities under CON conditions in order to become
familiarized with the exercise protocol. Self-selected intensities were used during the
familiarization sets so that the subject could practice the intended duty cycle consisting of
a five second isometric contraction followed by thirty seconds of recovery. The subject
was provided with five minutes of recovery following each of the familiarization sets.
The self-selected intensities were recorded during the first visit and used for subsequent
warm-up sets throughout the remainder of the investigation.
Following the completion of the familiarization/warm-up sets, each subject
completed three maximal voluntary isometric contractions (MVIC) at 90° of knee
25
flexion. Each MVIC was performed under CON conditions consisting of a five second
contraction duration followed by five minutes of recovery. Subsequent to the MVIC, the
subject completed one set of four repetitions of sub-maximal isometric knee extension for
each BFR condition. In order for the subject to reach the desired sub-maximal intensity a
line was placed on the computer monitor to indicate to the subject, via visual feedback,
the force needed for each target sub-maximal intensity. The sub-maximal target
intensities (20%MVC, 40%MVC, 60%MVC, 80%MVC) were randomized between test
days, while the BFR conditions (CON, IO, PO) were randomized between each exercise
set within each test day. Each contraction was held for five seconds at the target intensity
with 30 seconds of recovery between each repetition. Subjects were provided with 15
minutes of recovery following each set of exercise.
Surface Electromyography (sEMG) Techniques
Surface electromyography (sEMG) was used to examine the neuromuscular
activation of the vastus lateralis (VL-RMS) and vastus medialis (VM-RMS) during each
contraction. Prior to placement of the sEMG electrodes, the skin was shaved and
cleansed with an alcohol pad. Double differential sEMG electrodes (Delsys, Bagnoli 8Channel System, Boston, MA) with a fixed inter-electrode distance of 1 cm were placed
on the vastus lateralis and vastus medialis of the dominant thigh. The vastus lateralis
sEMG electrode was placed at an oblique angle approximately 3-5 cm proximal to the
patella just lateral to the midline over the muscle belly [103]. The vastus medialis sEMG
electrode was placed at an oblique angle approximately 2 cm medially from the superior
border of the patella within the distal third of the vastus medialis muscle belly [103]. The
26
raw sEMG signal was collected at a sampling frequency of 2,000 Hz using LabChart 7.0
(ADInstruments, Inc., Colorado Springs, CO).
Near-Infrared Spectroscopy (NIRS) Techniques
Frequency-domain multi-distance (FDMD) near-infrared spectroscopy (NIRS)
was used to continuously monitor absolute deoxy-hemoglobin (deoxy-[Hb+Mb]) and
oxy-hemoglobin (oxy-[Hb+Mb]) responses. Total hemoglobin concentration ([THC]), an
indicator of blood volume within the microvasculature, was calculated as the sum of the
deoxy-[Hb+Mb] and oxy-[Hb+Mb] signals. The NIRS system (Oxiplex TS, ISS,
Champaign, IL) was calibrated prior to each data collection session according to the
specifications provided by the manufacturer and was operated at wavelengths of 690 nm
and 830 nm with a sampling frequency of 2 Hz. It has been previously reported that the
deoxy-[Hb+Mb] signal is less sensitive to blood volume changes (Δ[THC]) compared to
the oxy-[Hb+Mb] signal [104] and that deoxy-[Hb+Mb] can be used as an estimation of
oxygen extraction [105, 106]. Although the microvascular deoxygenation response
within the vastus lateralis has been shown to be non-uniform throughout the muscle
during fatiguing exercise, the greatest microvascular deoxygenation response has been
observed at the middle region of the vastus lateralis during knee extension exercise
compared to the distal regions [107]. Therefore, the NIRS sensor was positioned midway
between the ASIS and the superior border of the patella over the muscle belly of the
vastus lateralis in the present investigation. Prior to placement of the NIRS sensor the
skin was shaved and cleansed with an alcohol pad. The NIRS sensor was covered with a
dark black cloth, in order to prevent stray visible light sources from affecting the data
acquisition, and secured with straps placed over the vastus lateralis muscle.
27
Data Processing
The highest MVIC during the first testing session was used to calculate all submaximal intensities (20%MVC, 40%MVC, 60%MVC, 80%MVC) throughout the entire
investigation. All sEMG and NIRS data were analyzed during the middle three seconds
of each five second isometric contraction. The raw sEMG data were amplified by a gain
of 1,000 (Bagnoli 8-Channel System, Delsys, Boston, MA), digitally filtered using a
band-pass filter (10Hz-500Hz) and then smoothed using a 50 millisecond root means
squared (RMS) window (LabChart 7.0, ADInstruments, Inc., Colorado Springs, CO).
The sEMG data was then normalized to an average of the sEMG data collected during all
three CON MVIC during each testing session and therefore, all sEMG data are
represented as a percentage of the MVIC (%MVIC).
All exercising NIRS data were normalized using a "physiological calibration", as
previously described [105]. After the completion of all exercise, external occlusion (250
mmHg) was applied to the distal thigh for approximately five minutes until the deoxy[Hb+Mb] and oxy-[Hb+Mb] signals reached plateaus. All NIRS data are expressed as a
percentage of the maximal deoxygenated plateau (%DP) according to the physiological
calibration [105].
Statistical Analysis
To determine if there were any significant differences in neuromuscular activation
of the vastus lateralis (VL-RMS) and/or vastus medialis (VM-RMS) during exercise a
two-way (BFR condition x sub-maximal intensity) analysis of variance (ANOVA) with
repeated measures was used. Two-way (BFR condition x sub-maximal intensity)
ANOVA with repeated measures was also completed for the microvascular
28
deoxygenation response (deoxy-[Hb+Mb]) and total hemoglobin concentration response
([THC]) during exercise. The target sub-maximal isometric force and produced submaximal isometric force during the isometric contractions were examined via a two-way
(force x sub-maximal intensity) ANOVA with repeated measures in order to determine
significant differences. All significant ANOVA results were followed by Tukey's post
hoc analysis in order to identify the specific differences. For all statistical comparisons,
significance was set a priori at p ≤ 0.05. All data are presented as mean ± SD. Statistical
analysis was completed using Sigma Stat software (Sigma Stat 3.5, Systat Software, San
Jose, CA).
3.3 - Results
Resting Blood Pressure & Applied Occlusion Pressure
The mean resting systolic blood pressure was 124 ± 10 mmHg, while the mean
resting diastolic blood pressure was 81 ± 4 mmHg. Therefore, the mean applied
occlusion pressure (130% SBP) used during this investigation was 162 ± 12 mmHg.
Isometric Force Results
No significant difference was found between target sub-maximal isometric force
and the generated sub-maximal isometric force at any of the sub-maximal contraction
intensities.
Surface Electromyography (EMG) Results
Although there was a significant increase in neuromuscular activation of both the
VL-RMS and VM-RMS with increasing sub-maximal exercise intensities (p < 0.001),
there was no difference in VL-RMS or VM-RMS between any of the BFR conditions
during any sub-maximal intensity (Figure 1 & Figure 2).
29
Near-Infrared Spectroscopy (NIRS) Results
When examined relative to the maximal deoxygenated plateau (DP), significant
differences were detected for deoxy-[Hb+Mb] (Figure 3) and [THC] (Figure 4) based
upon BFR condition. PO (105.4 ± 36.2%DP) resulted in a higher deoxy-[Hb+Mb]
compared to both CON (81.5 ± 28.8%DP) and IO (94.8 ± 30.7%DP) at a sub-maximal
intensity of 20%MVC (p < 0.001, p = 0.043). Furthermore, deoxy-[Hb+Mb] was also
significantly higher during IO compared to CON at 20%MVC (p = 0.009). At a submaximal intensity of 40%MVC, deoxy-[Hb+Mb] was greater during both PO (107.5 ±
20.1%DP, p <0.001) and IO (100.1 ± 14.0%DP, p = 0.014) compared to CON (87.4 ±
17.9%DP). During sub-maximal intensities of 60%MVC (p = 0.01) and 80% MVC (p =
0.007), deoxy-[Hb+Mb] was higher during PO (116.7 ± 19.8%DP, 115.2 ± 14.5%DP)
compared to CON (103.7 ± 23.6%DP, 101.5 ± 16.7%DP).
PO (101.6 ± 19.7%DP, p < 0.001) and IO (98.6 ± 21.2%DP, p < 0.001) elicited
higher [THC] compared to CON (91.0 ± 20.1%DP) at a sub-maximal intensity of
20%MVC. During exercise at 40%MVC, [THC] was greater during both PO (97.8 ±
9.6%DP, p < 0.001) and IO (96.6 ± 9.6%DP, p < 0.001) compared to CON (88.2 ±
7.9%DP). [THC] was higher during PO (102.5 ± 13.9%DP, p < 0.001) and IO (98.9 ±
12.2%DP, p = 0.044) compared to CON (95.0 ± 13.0%DP) at a sub-maximal intensity of
60%MVC. PO (90.9 ± 6.9%DP, p = 0.004) and IO (90.2 ± 8.6%DP, p = 0.012) resulted
in higher [THC] at a sub-maximal intensity of 80%MVC compared to CON (85.4 ± 6.0).
There were no differences in [THC] between PO and IO BFR conditions at 20%MVC,
40%MVC, 60%MVC, or 80%MVC.
30
3.4 - Discussion
In contrast to our initial hypothesis, the results of the present investigation demonstrated
no significant changes in neuromuscular activation during low-volume, isometric
exercise between BFR and CON conditions. More specifically, differing BFR occlusion
durations (immediate occlusion, IO; pre-occlusion, PO) did not elicit an immediate
substantial impact on neuromuscular activation during low-volume, isometric exercise at
a variety of sub-maximal exercise intensities (20%MVC, 40%MVC, 60%MVC,
80%MVC). In partial agreement with our second hypothesis, a longer occlusion duration
(PO) resulted in a greater deoxy-[Hb+Mb] response than immediate occlusion (IO),
however this was only observed at a low exercise intensity (20% MVC). Although PO
resulted in a greater deoxy-[Hb+Mb] response compared to CON at all tested exercise
intensities, IO only elicited in a greater deoxy-[Hb+Mb] response compared to CON at
low exercise intensities (20% MVC, 40%MVC). This observation could suggest that the
exercise-induced metabolic stress, as measured by NIRS, during IO exercise is attenuated
at high exercise intensities (60% MVC, 80% MVC). In addition, the present
investigation revealed that BFR (IO, PO) exercise caused higher microvascular [THC]
compared to CON exercise, however no difference in [THC] was observed between the
BFR (IO, PO) conditions at any sub-maximal intensity.
The conflicting results regarding neuromuscular activation observed during the
present investigation and the previous BFR isometric investigation [19] could be due to
differences in exercise volume and/or applied external occlusion pressures. During the
previous investigation [19] the duty cycle included a two second isometric contraction at
a sub-maximal intensity of 20%MVC followed by a two second recovery, this exercising
31
duty cycle (i.e., two second contraction, two second recovery) was continued for a
duration of four minutes. During the present investigation the exercise volume was
considerably lower as each subject performed three sets of four isometric repetitions.
The duty cycle of the present investigation included a five second contraction duration
followed by 30 seconds of rest between each isometric repetition. Unlike the highvolume exercise protocols typically used in previous BFR investigations [98, 99], a low
exercise volume was chosen for the present investigation in an attempt to negate the
influences that fatigue and/or increases in metabolic accumulation may have upon
neuromuscular activation. Therefore, the greater exercise volume that was performed in
the previous BFR isometric investigation [19] could have caused an increase in metabolic
accumulation, thus possibly leading to increased neuromuscular activation [108] that has
typically associated with BFR exercise [16-19].
It is also important to note that the external occlusion pressures utilized during the
BFR conditions throughout the two studies were different. This could have potentially
affected the neuromuscular activation outcome by creating a difference in the hypoxic
intramuscular environment, as suggested previously [19]. The previous investigation
[19] utilized an absolute occlusion pressure (200 mmHg) for all subjects that was higher
than the relative occlusion pressure used in the present investigation which was
determined by the subject's resting systolic blood pressure (130% SBP, 162 ± 12 mmHg).
Similar neuromuscular activation between BFR and CON conditions, as observed
in the present investigation, have been demonstrated during isotonic BFR exercise
elsewhere [109]. During the previous investigation [109] subjects performed three sets of
isotonic knee extension exercise at a sub-maximal intensity of 30%MVC to volitional
32
fatigue. The absolute occlusion pressure of 100 mmHg was applied at the beginning of
the first exercise set and released after the completion of the third exercise set. The
occlusion cuff remained inflated while the subject received 45 seconds of intermittent
recovery following the completion of each exercise set and therefore occlusion duration
was dictated by the number of repetitions performed to volitional fatigue. Although not
specified by the author, the number of repetitions performed to volitional fatigue under
BFR conditions decreased during subsequent exercise sets throughout the session,
however, no changes in neuromuscular activation were observed during the concentric
phase between the initial BFR exercise set and the fatiguing BFR exercise sets [109].
The combined findings of the previous investigation [109] and the present investigation
suggest that occlusion duration may not directly influence neuromuscular activation
during BFR exercise. However, high exercise volume and/or the magnitude of applied
external occlusion pressure used may elicit the higher neuromuscular activation
commonly observed with BFR exercise [16-19].
Previous investigations [97, 108] provides support that increases in
neuromuscular activation demonstrated via BFR exercise compared to CON exercise
could not only be dependent on reduced skeletal muscle oxygenation, as previously
hypothesized [19], but also be affected by intramuscular metabolic stress [80]. Increases
in metabolic stress could be due to the diminished venous return commonly associated
with BFR exercise [53, 110] thus resulting in the accumulation of metabolites and blood
volume within the exercising musculature. Therefore, in partial agreement with our
secondary hypothesis and a previous investigation performed with subjects at rest in the
supine position [95], the presence of occlusion (IO, PO) elicited greater deoxy-[Hb+Mb]
33
compared to CON while performing isometric exercise at various sub-maximal
intensities, suggesting a greater oxygen extraction [105, 106]. However, the deoxy[Hb+Mb] was not significantly different between IO and CON at 60%MVC and
80%MVC intensities. This result could indicate that an exercise intensity threshold
exists, in which, the difference in metabolic demand (i.e., deoxy-[Hb+Mb]) between IO
and CON exercise is attenuated due to an increasing demand during high intensity
(60%MVC, 80%MVC) exercise [111]. It has been previously demonstrated that there are
no additive benefits (i.e., muscular hypertrophy and strength) for the use of BFR
techniques during high-intensity exercise programs [112]. The attenuated deoxy[Hb+Mb] response observed during the present investigation may support the previous
finding [112].
In accordance with our secondary hypothesis, [THC] was greater during occluded
(IO, PO) exercise compared to CON exercise in the present investigation. This
observation could be explained by an accumulated blood volume within the area of
interrogation [113, 114], possibly due to the lack of venous return commonly associated
with BFR exercise [53, 110]. Although we can only speculate the change in
intramuscular metabolic stress during the present investigation, the findings of the present
investigation are consistent with an increased demand for oxygen (increased deoxy[Hb+Mb]) and/or accumulation of blood volume (increased [THC]) within the exercising
musculature. Despite these observations, the metabolic stress during the present
investigation (low-volume, isometric exercise) may not have reached the theoretical
threshold required to affect neuromuscular activation, as previously suggested [108]. The
increased [THC] observed in the present investigation is in agreement with the
34
phenomenon that has been previously reported in BFR literature known as "cellular
swelling" [80]. Cellular swelling has been associated with increases in protein synthesis
[115, 116], which has also been suggested to be a BFR training adaptation [38, 39].
However, the authors of the present investigation caution this immediate explanation, as
the increased [THC] could also reflect the accumulation of blood in adjacent
vessels/capillaries that were not fully recruited prior to the occlusion and/or muscle
contraction.
During the present investigation surface electromyography was only recorded
from the vastus lateralis and vastus medalis muscles during exercise. This is a limitation
to the present investigation as possible compensatory increases in neuromuscular
recruitment of other synergistic muscles [117] were not accounted for. Furthermore,
microvascular deoxygenation responses were only obtained at one point within the vastus
lateralis, while a non-uniform microvascular response to fatiguing exercise has been
previously documented [107]. However, it is important to note that the NIRS sensor
placement remained consistent throughout each exercise session for each subject in order
to reduce the within-subject variability between sessions. However, future investigations
should consider the effect of varied occlusion pressures on synergistic muscle groups as
well as the microvascular oxygenation response at multiple sites in the vastus lateralis
and other muscles.
3.5 - Conclusion
The primary purpose of this investigation was to observe if neuromuscular
activation and microvascular oxygenation was immediately affected from the application
of varying BFR occlusion durations. The exercise volume remained low compared to
35
previous BFR investigations [98, 99] in an attempt to negate the effects of fatigue and/or
metabolic byproduct accumulation on neuromuscular activation. In conclusion,
neuromuscular activation does not seem to be affected solely from the application of
external occlusion durations (i.e., IO and PO) but possibly due to increased metabolic
stress (i.e., high applied external occlusion pressure, high exercise volume and short
recovery periods). PO exercise elicited a greater deoxy-[Hb+Mb] response compared to
IO exercise at an exercise intensity of 20% MVC. In addition, the increased deoxy[Hb+Mb] response during IO exercise compared to CON exercise was only observed
during low-intensity exercise (20% MVC, 40% MVC). These findings could suggest that
the effect of the varied BFR conditions may be attenuated during higher intensity
exercise. Furthermore, all BFR conditions displayed a greater [THC] during exercise
compared to CON exercise, thus indicating the presence of an increased microvascular
blood volume within the area of interrogation. According to the accumulated results of
previous BFR investigations and the present investigation it is suggested that BFR
occlusion duration alone may not be the primary stimulus for the increase in
neuromuscular activation commonly associated with BFR exercise. Furthermore,
providing an adequate metabolic stress (i.e., high applied occlusion pressure, high
exercise volume, and/or short recovery periods) may be a driving mechanistic link for the
observed health and performance improvements associated with BFR exercise.
36
Figure 3-1 No significant difference in neuromuscular activation of the VL-RMS was
observed between blood flow restriction conditions at any of the sub-maximal intensities
(p > 0.05).
37
Figure 3-2 No significant difference in neuromuscular activation of the VM-RMS was
observed between blood flow restriction conditions at any of the sub-maximal intensities
(p > 0.05).
38
Figure 3-3 Significantly higher deoxygenated hemoglobin (deoxy-[Hb+Mb]) was
observed with immediate occlusion (IO) and pre-occlusion (PO) blood flow restriction
conditions during low-intensity (20%MVC, 40%MVC) exercise compared to control
(CON) exercise. Deoxy-[Hb+Mb] was significantly higher with PO compared to IO
during exercise at 20%MVC. Significantly higher deoxy-[Hb+Mb] was observed during
high-intensity (60%MVC, 80%MVC) exercise with PO compared to CON.
*Significantly different compared to CON, p ≤ 0.05. #Significantly different compared
to IO, p ≤ 0.05.
39
Figure 3-4 A higher total hemoglobin concentration ([THC]) was observed during the
immediate occlusion (IO) and pre-occlusion (PO) blood flow restriction conditions
compared to the free-flow (control, CON) condition. *Significantly different compared to
CON, p ≤ 0.05.
40
Chapter 4
Acute Effects of Blood Flow Restriction During Heavy Intensity Cycling Exercise
4.1 - Introduction
Blood flow restriction (BFR) training using low-intensity loads (20-40% one
repetition maximum, 1RM) have been previously shown to increase skeletal muscle
strength [17] and hypertrophy (i.e., increased cross-sectional area) [17, 37] within
resistance training models. Furthermore, increases in vascular endothelial growth factor
receptor 2 (VEGF-R2) concentrations have been previously reported following BFR lowintensity knee extension exercise at exercise intensities of 20% 1RM [53] and 40% 1RM
[43]. VEGF-R2 has been established as a potent exercise-induced angiogenic stimulator
[48] and has been associated with the formation of new capillaries and improvements in
oxygen delivery to exercising skeletal muscle [50-52]. Additionally, previous
investigations have demonstrated advantageous cardiovascular training adaptations
subsequent to BFR low-intensity cardiovascular (i.e., walking, cycling) training, resulting
in increased peak oxygen uptake (VO2pk) [14, 15, 21], muscular endurance (time to
exhaustion) [14, 20, 21], citrate synthase (CS) [20] and anaerobic capacity (i.e., Wingate
test) [15]. Significant increases in skeletal muscle strength [13] and hypertrophy [13, 14]
41
have been demonstrated concurrently with the cardiovascular adaptations following BFR
low-intensity cardiovascular training.
BFR low-intensity cardiovascular training may be a favorable alternative exercise
approach for populations with a lowered exercise tolerance due to the advantageous
cardiovascular adaptations, concurrent skeletal muscle strength and hypertrophy
increases and relatively low exercise intensities used during training. However, despite
the beneficial outcomes associated with BFR cardiovascular training, the physiological
mechanism(s) responsible for the training adaptations are still under debate. Therefore it
is imperative to systematically evaluate the physiological effects of BFR low-intensity
cardiovascular exercise so that an effective exercise prescription may be created for BFR
cardiovascular training programs.
For instance, an acute bout of BFR cycling exercise has been shown to decrease
exercising stroke volume while increasing exercising heart rate at a variety of submaximal cycling intensities (20% VO2pk, 40% VO2pk, 60%VO2pk) [45]. During this
perturbation of exercising stroke volume and heart rate, cardiac output is maintained
similar to a free-flow (control) exercise levels measured at the same sub-maximal cycling
intensities [45]. The lowered exercising stroke volume during BFR cycling exercise may
be due to the diminished venous return commonly associated with venous pooling within
the muscle during BFR exercise [53, 110]. Although, exercising stroke volume and heart
rate have been shown to be affected by BFR techniques, exercising oxygen uptake
measured at the mouth (VO2) was not significantly different during sub-maximal BFR
and free-flow (control) cycling exercise [45]. However, exercising VO2 has been shown
to be significantly higher during BFR walking compared to free-flow (control) walking
42
exercise [13]. According to Fick's equation, the higher exercising VO2 observed during
BFR walking [13] could be due to an increased oxygen extraction (A-VO2diff) previously
demonstrated during BFR exercise [81], despite similar cardiac output values [45].
It has also been previously proposed that the cardiovascular adaptations observed
subsequent to a BFR training program may be due to peripheral adaptations [20-23].
However, little information is known how BFR cardiovascular exercise affects the
neuromuscular activation and microvascular oxygenation of the exercising muscles.
Therefore, the primary purposes of the present investigation was 1) to determine the
metabolic, neuromuscular activation, and microvascular oxygenation responses to an
acute bout of BFR cycling exercise at a variety of occlusion stimuli (control, low, high)
and 2) to evaluate the subsequent effect on VEGF-R2 concentrations following a single
BFR cycling. Varied occlusion stimuli (control, low, high) were used in the present
investigation to determine the acute metabolic, neuromuscular activation, and
microvascular oxygenation responses to perturbations in intramuscular hypoxia and
metabolite accumulation. The primary hypothesis was that a suprasystolic (high, HO)
occlusion pressure would elicit a greater microvascular deoxygenation (deoxy-[Hb+Mb])
response and higher neuromuscular activation during BFR exercise compared to control
(CON) exercise, as measured using near-infrared spectroscopy (NIRS) and surface
electromyography (sEMG) techniques, respectively. The secondary hypothesis was that
a greater plasma VEGF-R2 concentration would occur following HO cycling exercise
compared to CON exercise.
43
4.2 - Methods
Eight healthy, recreationally active, male subjects participated within the present
research investigation. The purpose, benefits, and risks associated with participation
were explained and each subject read and voluntarily signed an informed consent form
that was in agreement with the Deceleration of Helsinki and approved by the university's
institutional review board for human subjects prior to participation. Each subject
completed medical health history and activity level questionnaires and the answers to the
questionnaires were used for subject inclusion and exclusion criteria. Any subject that
had previously been diagnosed with a metabolic, pulmonary, and/or cardiovascular
disease, including hypertension, was excluded from the investigation. In addition, any
subject that had been diagnosed with deep vein thrombosis, any blood clotting disorder,
and/or an orthopedic-related injury (within the last 12 months) was also excluded from
participation within the investigation. Each subject was asked to refrain from
participating in any strenuous physical activity 24 hours prior to each data collection
session. Each session was scheduled at approximately the same time of day for each
subject with at least 48 hours between each subsequent visit.
Exercise Testing
During the first visit, anthropometric measurements were recorded including age
(years), height (meters, m), weight (kilograms, kg), resting blood pressure (mmHg), and
body composition (percent body fat, %fat). At the beginning of each session the subject
was seated and remained at rest for five minutes prior to measuring blood pressure. All
blood pressure measurements were obtained with the upper arm supported at heart level
with the subject seated in an upright position. The total body composition was
44
determined by utilizing an air displacement method known as the BodPod Body
Composition System (BodPod Express EX, Cosmed, Rome, Italy). All subject
demographic data are displayed in Table 1 below.
Next each subject completed an incremental ramp test to volitional fatigue on a
stationary cycle ergometer (Excalibur Sport, Lode, The Netherlands) using a forcing
function of 20 watts per minute (W/min). During the progressive ramp exercise test the
subjects were asked to maintain a pedaling cadence of 80-100 revolutions per minute
(rpm). The exercise test was terminated when the pedaling cadence fell below 50 rpm in
spite of strong verbal encouragement or the subject achieved volitional fatigue.
Pulmonary gas exchange was recorded breath by breath using a commercially available
metabolic measurement system (SensorMedics, Vmax, Loma Linda, CA). The metabolic
measurement system was calibrated prior to each testing session according to the
specifications provided by the manufacturer. The flow sensor was calibrated with a 3.0
liter syringe, while the oxygen (O2) and carbon dioxide (CO2) analyzers were calibrated
using reference gases of known concentrations. All pulmonary gas exchange data was
averaged over 10 second bins following the completion of the ramp assessment and was
used in order to estimate the lactate threshold (LT) and identify the peak oxygen uptake
(VO2pk). The LT was estimated using the V-slope, end-tidal gases, and ventilatory
equivalents as described previously [57, 58]. VO2pk was defined as the highest O2 uptake
(VO2) value (using the 10 s averaged data) achieved during the maximal ramp exercise
test.
Heavy Intensity Constant Work Rate Exercise Protocol
45
Each subject completed a 20 minute heavy intensity (>LT) square wave exercise
bout at a work rate equivalent to 10% above their LT (LT+10%; 157 ± 44.5 W; 54 ± 8%
VO2pk) combine with a randomized BFR condition on three separate occasions. The BFR
conditions used in the present investigation included control (CON, 0 mmHg), low
occlusion (LO, 50 mmHg), and high occlusion (HO, 164.0 ± 6.1 mmHg). The HO
condition was equivalent to 130% of the subject's resting systolic blood pressure (130%
SBP) and is consistent with occlusion pressures used in previous BFR investigations [15,
36, 42, 53, 101].
The distance from the anterior superior iliac spine (ASIS) to the superior border
of the patella was measured and an occlusion cuff (Hokanson, SC5, Bellevue, WA, 6.0
cm width) was positioned 33% of the distance distal to the ASIS, bilaterally. This
positioning of the occlusion cuff is similar to the cuff position used in a previous BFR
exercise investigation [100]. Surface electromyography (sEMG) and near-infrared
spectroscopy (NIRS) techniques were used to measure the neuromuscular activation and
microvascular oxygenation during the heavy intensity cycling exercise bout, respectively.
Pulmonary gas exchange was also collected breath-by-breath during the cycling exercise
for the determination of oxygen uptake (VO2).
Each subject completed a 5 minute cycling warm-up at 20 W followed by a
transition in work rate corresponding to LT+10% for 20 minutes. The subject was asked
to maintain a pedaling cadence between 80 and 100 rpm during exercise. During the LO
and HO conditions the occlusion cuffs were immediately inflated (LO = 50 mmHg, HO =
130%SBP, 164 ± 6 mmHg) at the beginning of exercise using a rapid cuff inflation
system (Hokanson, E20 Rapid Cuff Inflator, Bellevue, WA). Following the completion
46
of the exercise bout the occlusion cuffs were immediately deflated and the work rate was
reduced to 20 W for a 5 minute cool-down period. Subsequent to the cool-down, the
subject was transferred from the stationary cycle ergometer to a chair in order to collect
the post-exercise arterialized venous blood samples.
Blood Sampling
Arterialized venous blood was sampled before and after each heavy intensity
exercise bout for determination of plasma vascular endothelial growth factor receptor-2
(VEGF-R2) and plasma lactate concentrations. Prior to the exercise bout, the subject
rested in a supine position as a percutaneous Teflon catheter (22 gauge, Smiths Medical
International Ltd, Rossendale Lancashire, UK) was placed into the dorsal venous plexus
of the hand and secured by tape. The blood samples were "arterialized" by warming the
forearm and hand with use of a heating pad, as previously described [118, 119]. The
arterialized-venous blood was sampled during baseline cycling (20W), immediately post
exercise and at 10, 30 and 60 minutes post exercise. All arterialized-venous blood
samples were immediately centrifuged and separated (16,100 g, 10 minutes;
Microcentrifuge 5415R, Eppendorf, Hauppauge, NY). All plasma samples were
extracted and then stored in a -80°C freezer until later analysis. An enzyme-linked
immunosorbent assays (ELISA, Human VEGF-R2 ELISA, RayBiotech, Norcross, GA)
was used to determine plasma VEGF-R2 concentrations in the arterialized-venous
samples at each sample interval. Plasma lactate concentrations ([lactate]) was determined
via a blood gas analyzer (Stat Profile pHOx Plus L, Nova Biomedical, Waltham, MA) at
baseline and immediately post exercise.
Surface Electromyography (sEMG) Techniques
47
Surface electromyography (sEMG) was used to examine the neuromuscular
activation of the vastus lateralis (VL-RMS) and vastus medialis (VM-RMS) during
cycling exercise for each occlusion condition. Prior to placement of the sEMG
electrodes, the skin was shaved and cleansed with an alcohol pad. Double differential
sEMG electrodes (Delsys, Bagnoli 8-Channel System, Boston, MA) with a fixed interelectrode distance of 1 cm were placed on the vastus lateralis and vastus medialis of the
left thigh. The vastus lateralis sEMG electrode was placed at an oblique angle
approximately 3-5 cm proximal to the patella just lateral to the midline over the muscle
belly [103]. The vastus medialis sEMG electrode was placed at an oblique angle
approximately 2 cm medially from the superior border of the patella within the distal
third of the vastus medialis muscle belly [103]. The raw sEMG signal was collected at a
sampling frequency of 2,000 Hz using LabChart 7.0 (ADInstruments, Inc., Colorado
Springs, CO).
Near-Infrared Spectroscopy (NIRS) Techniques
Frequency-domain multi-distance (FDMD) near-infrared spectroscopy (NIRS)
was used to continuously monitor absolute deoxy-hemoglobin (deoxy-[Hb+Mb]) and
oxy-hemoglobin (oxy-[Hb+Mb]) responses. Total hemoglobin concentration ([THC]), an
indication of blood volume within the microvasculature, was calculated as the sum of the
deoxy-[Hb+Mb] and oxy-[Hb+Mb] signals. The NIRS system (Oxiplex TS, ISS,
Champaign, IL) was calibrated prior to each data collection session according to the
specifications provided by the manufacturer and operated at wavelengths of 690 nm and
830 nm with a sampling frequency of 2 Hz. It has been previously reported that the
deoxy-[Hb+Mb] signal is less sensitive to changes in blood flow perfusion (reflected by
48
Δ[THC]) compared to the oxy-[Hb+Mb] signal [104] and that the deoxy-[Hb+Mb]
response is an acceptable estimation of oxygen extraction [105, 106]. Although the
microvascular deoxygenation response within the vastus lateralis has been shown to be
non-uniform throughout the muscle during fatiguing exercise, the greatest microvascular
deoxygenation response has been observed at the middle region of the vastus lateralis
during knee extension exercise compared to the distal regions [107]. Therefore, the
NIRS sensor was positioned midway between the ASIS and the superior border of the
patella over the muscle belly of the vastus lateralis in the present investigation. Care was
taken to place the NIRS sensor in the same position for each exercise condition. Prior to
placement of the NIRS sensor the skin was shaved and cleansed with an alcohol pad.
The NIRS sensor was covered with a dark black cloth, in order to prevent stray visible
light sources from affecting the data acquisition, and secured with straps placed over the
vastus lateralis muscle.
Data Processing
The raw sEMG data were amplified by a gain of 1,000 (Bagnoli 8-Channel
System, Delsys, Boston, MA), digitally filtered using a band-pass filter (10Hz-500Hz)
and smoothed using a 50 millisecond root means squared (RMS) window. All
neuromuscular activation, microvascular oxygenation and oxygen uptake data was
averaged into 10 second bins. Then neuromuscular activation, microvascular
oxygenation and oxygen uptake measurements were analyzed in 60 second bins at 1, 5,
10, 15, and 19 minutes into the heavy intensity (>LT) exercise bout. All sEMG data was
normalized as a percentage of the baseline neuromuscular activation (%BL) that occurred
during the last 30 seconds of the warm-up cycling (20W) prior to the heavy intensity
49
work rate transition, similar as previously described [120]. All NIRS data was
normalized as a percentage of the baseline microvascular oxygenation (%BL) that
occurred during the last 30 seconds of the warm-up cycling (20 W) prior to the heavy
intensity work rate transition.
Statistical Analysis
A two-way (occlusion condition x time) analysis of variance (ANOVA) with
repeated measures was used to identify differences in the dependent variables (plasma
VEGF-R2 concentrations, [lactate], neuromuscular activation (RMS), deoxy-[Hb+Mb],
[THC], and oxygen uptake). Tukey's post-hoc analysis was used in order to find
significance when appropriate. Statistical significance was set at a priori of p ≤ 0.05. All
values are expressed as the group mean ± standard deviation (SD) unless otherwise
stated. All statistical analyses was completed using Sigma Stat software (Sigma Stat 3.5,
Systat Software, San Jose, CA).
4.3 - Results
Surface Electromyography (sEMG) Results
HO (202.9 ± 50.2%BL) resulted in a lower neuromuscular activation of the vastus
lateralis (VL-RMS) compared to CON (256.2 ± 43.2 %BL) during the last minute of the
heavy intensity exercise bout (p = 0.034). The last minute (256.2 ± 43.2%BL) of the
heavy intensity exercise bout elicited a greater neuromuscular activation of the VL-RMS
compared to the first minute (196.4 ± 37.4%BL) of the heavy intensity exercise bout
during the CON condition (p = 0.021). There were no significant differences observed in
neuromuscular activation at any of the time points examined within or between the
occlusion conditions for either the VL-RMS or vastus medialis (VM-RMS).
50
Near-Infrared Spectroscopy (NIRS) Results
Due to technical difficulties with the computer, the microvascular oxygenation
response for one subject could not be retrieved and therefore the NIRS responses are for
seven of the subjects. The HO condition resulted in greater deoxy-[Hb+Mb] compared to
CON at 1 minute (HO = 144.8 ± 14.7%BL; CON = 120.1 ± 19.9%BL; p = 0.010), 5
minutes (HO = 159.1 ± 14.5%BL; CON = 133.5 ± 16.8%BL; p = 0.007), and the last
minute of exercise (HO = 167.2 ± 13.0%BL; CON = 146.6 ± 15.7%BL; p = 0.041). HO
also resulted in greater deoxy-[Hb+Mb] compared to LO at 5 minutes (HO = 159.1 ±
14.5%BL; LO = 138.6 ± 16.8%BL; p = 0.030) and the last minute of exercise (HO =
167.2 ± 13.0%BL; LO = 146.0 ± 19.5%BL; p = 0.036). During CON, deoxy-[Hb+Mb]
was greater during the end of exercise (10, 15 and 19 minutes) compared to the beginning
of exercise (1 and 5 minutes). Additionally, deoxy-[Hb+Mb] was greater at 5 minutes
compared to the first minute of the CON exercise bout. LO exercise resulted in greater
deoxy-[Hb+Mb] during the end of exercise (10, 15 and 19 minutes) compared to the first
minute of exercise. Furthermore, HO exercise elicited greater deoxy-[Hb+Mb] during
the end of exercise (5, 10, 15 and 19 minutes) compared to the first minute of exercise.
In addition, HO resulted in higher [THC] compared to CON at 5 minutes (HO =
112.9 ± 7.6%BL; CON = 105.9 ± 2.6%BL; p = 0.010), 10 minutes (HO = 113.4 ±
9.8%BL; CON = 106.6 ± 3.5%BL; p = 0.013), and 15 minutes (HO = 112.8 ± 7.1%BL;
CON = 106.9 ± 5.0%BL; p = 0.033) of the heavy intensity bout of exercise. HO also
resulted in greater [THC] at 10 minutes compared to the first minute of exercise.
Oxygen Uptake (VO2) Results
51
There was no significant differences observed in VO2 during the heavy intensity
exercise between any of the BFR conditions examined (CON, LO, HO) within the
exercising time points (1 min, 5 min, 10 min, 15 min, 19 min). However, VO2 was
greater during the following time points (5 min, 10 min, 15 min, 19 min) compared to 1
minute within all exercise conditions.
Arterialized Venous Blood Sampling Results
A significant main effect for occlusion condition was detected for VEGF-R2 as
HO (78.7 ± 1.8 pg/mL) was higher compared to CON (CON = 77.7 ± 1.0 pg/mL; p =
0.030). However, there were no significant differences detected in VEGF-R2 subsequent
to the heavy intensity exercise bout between any of the exercising conditions (CON, LO,
HO) within the timed blood samples (Pre, 10 Post, 30 Post, 60 Post).
As expected, a significant main effect for time was detected for plasma [lactate]
as immediate post exercise (10.1 ± 4.3 mmol/L) was higher compared to baseline (BSL =
2.8 ± 1.2 mmol/L; p = 0.002). However, no significant difference was observed for
plasma [lactate] between any of the occlusion conditions (CON, LO, HO) within the
timed blood samples (baseline and immediately post exercise).
4.4 - Discussion
In contrast to our first hypothesis and previous BFR investigations [16-19], the
neuromuscular activation during heavy intensity (VT+10%) cycling exercise was not
different, or even lower during the last minute of exercise, during HO compared to both
CON and LO within the vastus lateralis (Figure 4.1). It has been previously suggested
that hypoxia causes a decline in neuromuscular activation (root means squared, RMS)
following a sustained sub-maximal isometric contraction [121]. The repetitive cyclic
52
contractions performed at high contraction velocities (80-100 rpm) during the cycling
exercise potentially over time could have elicited a similar response to the muscle thus
potentially explaining the declined neuromuscular activation found within the vastus
lateralis towards the end of exercise (19 min). However, this relationship between
neuromuscular activation and the effects of hypoxia from BFR techniques during
cardiovascular exercise should be investigated further. It is important to note, that the
increase in neuromuscular activation reported previously [16-19] have been observed
using resistance exercise models, in which the contraction duration and contraction
velocity differ from cycling exercise. The results of the present investigation suggest that
exercise mode (i.e., resistance exercise, cardiovascular exercise) may influence the
effects of BFR on neuromuscular activation. In addition, the effects of varied contraction
velocities on neuromuscular activation during BFR exercise, during both resistance and
aerobic exercise modes, warrants further investigation.
However, supporting our first hypothesis, HO elicited a greater deoxy-[Hb+Mb]
compared to CON and LO during the beginning and end of the heavy intensity cycling
exercise (Figure 4.2). The deoxy-[Hb+Mb] signal provides an estimate of the oxygen
extraction (A-VO2diff) within the field of interrogation [114] and has been demonstrated
as being insensitive to blood volume changes [104, 122]. The increased deoxy-[Hb+Mb]
during HO exercise supports the previous finding of a greater oxygen extraction during
ischemic cycling exercise [81]. However, similar to a previous BFR investigation [45],
the present investigation found no difference in exercising VO2 between any of the
exercising conditions (Figure 4.4), despite the greater deoxy-[Hb+Mb] signal during HO
exercise. According to Fick's equation, this finding could suggest that the perturbation
53
caused by HO may have affected cardiac output in some way, however, this was
managed by the adjustment of an increased oxygen extraction (i.e., increased deoxy[Hb+Mb]). The author's of the present investigation can only speculate the effect that
BFR cardiovascular exercise has on cardiac output as it was not directly measured during
the present investigation and deoxy-[Hb+Mb] is only used as a surrogate for oxygenation
extraction [114]. This speculation differs from a previous BFR investigation [45], that
observed no difference in VO2 or cardiac output between sub-maximal BFR and control
cycling exercise when stroke volume and heart rate were measured non-invasively.
Further evidence is required to determine the hemodynamic effects of BFR cycling
exercise. However, the higher deoxy-[Hb+Mb] observed during HO exercise, could
suggest the presence of a greater hypoxic intramuscular environment [105, 106], thus
providing support for the lowered neuromuscular activation demonstrated during HO
exercise.
Increases in [THC], a measurement of blood volume within the area of
interrogation [114], was observed during HO compared to CON during the heavy
intensity cycling exercise (Figure 4.3). The elevated [THC] could be explained by the
presence of venous pooling within the exercising musculature, as a reduction in venous
return has previously been associated with BFR exercise [53, 110]. It has been proposed
that the venous pooling related to BFR exercise could promote "cellular swelling", a
potential mechanistic link to the increase in hypertrophy following BFR training [80].
However, the authors of the present investigation caution this immediate explanation as
the increased [THC] during exercise could also be explained by recruitment of adjacent
vessels within the area of interrogation during exercise. Furthermore, [THC] did not
54
differ between CON and LO exercising conditions at any point during the exercise bout,
thus suggesting that the low external occlusion pressure (LO, 50 mmHg) applied may not
be a sufficient stimulus if venous pooling is a required BFR stimulus for training
adaptations to occur.
Contrary to our second hypothesis, plasma VEGF-R2 concentrations were not
altered from baseline values when compared between the exercise conditions within time
(Table 4.2), although a significant main effect was detected as HO elicited higher plasma
VEGF-R2 concentrations when compared to CON. It is possible that plasma VEGF-R2
continued to rise after the blood sample collections for the present investigation as it has
been suggested that peak plasma VEGF-R2 concentration occurs approximately 2 to 4
hours post exercise [123] and samples were obtained at 10, 30, and 60 minutes post
exercise during the present investigation. However, significant increases in plasma
VEGF-R2 have been detected 45-60 minutes post exercise [123]. Therefore, it could be
suggested that a detectable increase in plasma VEGF-R2 should have been discovered
during the blood sample collections of the present investigation, if an increase were
present, even if the plasma VEGF had not reached peak concentrations subsequent to
exercise.
Despite the possible sample timing differences, previously, low intensity (20%
one repetition maximum, 1RM) BFR knee extension exercise has shown significant
increases in plasma VEGF-R2 during exercise and 10 and 30 minutes post exercise [53].
However, similar to the present results, no change in plasma VEGF-R2 has also been
demonstrated following 40% 1RM BFR knee extension exercise at 4 and 24 hours post
exercise [43]. Despite no difference in plasma VEGF-R2 following BFR knee extension
55
exercise, significant increases in skeletal muscle expression of VEGF-R2 was observed 4
hours subsequent to BFR knee extension exercise via muscle biopsy samples [43]. Two
factors that could potentially explain the results of the previous and present investigations
findings include 1) exercise modes and 2) fatigue status of the subject. The exercise
mode could have affected the plasma VEGF-R2 response as both of the previous
investigations [43, 53] that have demonstrated increases in plasma VEGF-R2 have used a
resistance exercise model during BFR exercise rather than a cardiovascular exercise
model. In addition, BFR resistance exercise has previously been reported to increase the
neuromuscular activation of the exercising muscles [16-19], which was not observed
during BFR cardiovascular exercise during the present investigation (Graph 4.1).
Significant elevations in VEGF have been detected (in animal models) subsequent to
increased neuromuscular activation [78, 124]. Although only speculation, it could be
possible that the increased neuromuscular activation observed during BFR resistance
exercise could be associated with the increased VEGF-R2 and neither response
(neuromuscular activation, VEGF-R2) are associated with BFR cycling exercise.
Furthermore, the fatigue status of the subject could potentially affect the plasma
VEGF-R2 response as the subjects of the previous investigations [43, 53] were asked to
perform exercise to volitional fatigue whereas the subjects of the present investigation
only completed 20 minutes of cycling exercise and where not fatigued at the end of the
cycling exercise bout. In support of the fatigue response, no significant increases in
plasma lactate were observed between any of the cycling conditions immediately post
exercise (Table 4.3), suggesting that the metabolic stress of each cycling exercise
condition were similar.
56
4.5 - Conclusion
The primary objective of the present investigation was to determine the acute
physiological responses to BFR cycling exercise in an attempt to provide a mechanistic
link to the previously observed increases in VO2pk following BFR training [14, 15, 21].
According to the present results, VO2 does not appear to be affected by heavy intensity
BFR cycling exercise. However, the perturbations caused by the application of BFR
(HO) within the present investigation was managed by a more localized response as
oxygen extraction increased (i.e., increased deoxy-[Hb+Mb]). Furthermore, no changes
were detected in neuromuscular activation between exercising conditions with the
exception for end exercise where a significant decline in neuromuscular activation was
observed possibly due to limited O2 availability. Finally, conflicting with previous BFR
resistance exercise investigations, the present investigation demonstrated that an acute
bout of heavy intensity cycling exercise did not affect the subsequent plasma VEGF-R2
response although increases in plasma [lactate] where observed. This finding provides
evidence that the plasma VEGF-R2 response subsequent to the performance of BFR
exercise may be more dependent upon exercise mode (cycling exercise, resistance
exercise).
57
Figure 4-1 Neuromuscular activation of the vastus lateralis was significantly lower for
high occlusion cycling (HO, green bar) compared to control cycling (CON, black bar)
during the last minute of the heavy cycling exercise. *Significantly different from CON
(p < 0.05). +Significantly different from LO (p < 0.05).
58
Figure 4-2 High occlusion cycling (HO, green bar) elicited greater microvascular
deoxygenation (Deoxy-[Hb+Mb]) compared to control cycling (CON, black bar) at one,
five, and nineteen minutes of the heavy cycling exercise bout. HO cycling resulted in
greater deoxy-[Hb+Mb] compared to low occlusion cycling (LO, red bar) at five and
nineteen minutes of the heavy cycling exercise bout. *Significantly different from CON
(p < 0.05). +Significantly different from LO (p < 0.05).
59
Figure 4-3 High occlusion cycling (HO, green bar) resulted in significantly greater total
hemoglobin concentration ([THC]) compared to control cycling (CON, black bar) at five,
ten, and fifteen minutes of the heavy cycling exercise bout. *Significantly different from
CON (p < 0.05). +Significantly different from LO (p < 0.05).
60
Figure 4-4 No significant difference was detected for exercising oxygen uptake (VO2)
between any of the exercise conditions during any of the time points analyzed.
*Significantly different from CON (p < 0.05). +Significantly different from LO (p <
0.05).
61
Table 4-1 Subject Demographics
Subject Characteristic
Mean ± SD
Age (yrs)
24 ± 3
Height (m)
1.83 ± 0.08
Weight (kg)
100.9 ± 46.3
Body Composition (%)
15.2 ± 7.3
VO2pk (mL/kg/min)
45.3 ± 13.7
VT+10% (%VO2pk)
54.0 ± 7.9
VT+10% (W)
157 ± 44
Resting Systolic Blood Pressure (mmHg)
126 ± 5
Resting Diastolic Blood Pressure (mmHg)
80 ± 2
Occlusion Pressure (mmHg)
164 ± 6
62
Table 4-2 Plasma Vascular Endothelial Growth Factor Receptor 2 (VEGF-R2)
Concentrations
Time
Plasma [VEGF] (pg/mL)
CON
LO
HO
Baseline Ex (20W)
77.7 ± 1.2
78.5 ± 1.1
79.3 ± 1.9
10 Min Post Ex
77.9 ± 1.1
78.7 ± 0.9
79.1 ± 2.2
30 Min Post Ex
77.5 ± 1.1
78.0 ± 1.1
78.2 ± 1.6
60 Min Post Ex
77.7 ± 1.0
78.8 ± 2.6
78.2 ± 1.4
63
Table 4-3 Plasma Lactate Concentrations
Time
Plasma Lactate (mmol/L)
CON
LO
HO
Baseline Ex (20W)
2.7 ± 1.2
3.1 ± 1.7
2.6 ± 0.8
Immediately Post
Exercise
9.8 ± 5.2*
9.8 ± 5.2*
10.6 ± 2.2*
Plasma lactate concentration ([lactate]) increased immediately post exercise compared to
baseline exercise in all occlusion conditions (control, low occlusion, high occlusion).
*Significantly different from Baseline Exercise (p < 0.05).
64
Chapter 5
Effects of Blood Flow Restriction Low Intensity Interval Training on Cardiovascular
Endurance and Maximal Strength in Healthy Adults
5.1 - Introduction
Short-term, low volume, high intensity interval training (HIIT) programs have
been reported to promote mitochondrial biogenesis [7, 33] and elicit rapid training
improvements in peak oxygen uptake (VO2pk) [8, 10, 56], estimated lactate threshold
(LT) [8], oxidative phosphorylation capacity [8, 56], and exercise time trials performance
[7]. HIIT is an attractive alternative to traditional cardiovascular exercise programs due
to the rapid onset of training improvements while significantly reducing exercise volume
(~80-90%) [8, 9]. The reduction in exercise volume associated with HIIT is an important
factor when attempting to integrate exercise programs into a daily routine as the most
highly reported cause for adults not to exercise is due to time constrained schedules [5,
6].
However, HIIT sessions are composed of repeated intermittent high-intensity
exercise bouts followed by low-intensity exercise bouts [28]. The high-intensity bouts of
exercise typically equate to an "all-out effort" [9] and/or near-maximal (≥90% VO2pk ) [7,
65] efforts. Although HIIT programs have been previously incorporated into clinical
populations [69, 125, 126], these required high exercise intensities may become a
65
deterrent for some exercising populations (i.e., novice, low exercise tolerance, etc) who
do not like high effort activities and therefore may negatively affect exercise retention.
An alternative exercise method, known as blood flow restriction (BFR) exercise,
has been reported to concurrently increase VO2pk, skeletal muscle strength and skeletal
muscle hypertrophy while performing low-intensity (i.e., walking, cycling)
cardiovascular training [13-15]. However, to the author's knowledge the effects of BFR
low-intensity cardiovascular training on sub-maximal aerobic capacity (estimated LT
based upon the pulmonary gas exchange data and muscle oxidative phosphorylation as
represented by the time constant for phase II oxygen uptake kinetics [8, 56]) have yet to
be determined. Therefore, the primary objective of the present research investigation was
to determine if a short-term, low volume (6 exercise sessions, 2 weeks) BFR low
intensity interval training (BFR-LIIT) program, performed on a stationary cycle
ergometer, would result in significant training adaptations (VO2pk, LT, τVO2, skeletal
muscle strength). The second objective of the present investigation was to compare any
of the training adaptations observed following BFR-LIIT to the training adaptations
elicited by a short-term, low volume HIIT program. We hypothesize that both BFR-LIIT
and HIIT will elicit significant increases in VO2pk and LT while also speeding the time
constant of the phase II oxygen uptake kinetics (i.e., decreased τVO2). However, we also
hypothesize that BFR-LIIT will increase skeletal muscle strength subsequent to training
while there will be no change in strength measurements following HIIT.
In order to better prescribe any exercise program it is vital to have a basic
understanding of the acute (one session) exercise stimulus. Although the exact
mechanism(s) (i.e., hypoxic intramuscular environment [19], metabolic byproduct
66
accumulation [80]) explaining BFR exercise and the resulting training adaptations are
currently still under debate, some evidence suggests that the training adaptations (i.e.,
increased VO2pk) following BFR cardiovascular training may occur due to peripheral
adaptations [20-23]. Therefore, to provide additional information on the acute exercise
response neuromuscular activation (EMG), microvascular oxygenation (NIRS), oxygen
uptake (VO2), and ratings of perceived exertion (RPE) were collected during the first
training session. We hypothesized that HIIT will elicit an increased neuromuscular
activation, VO2 and RPE compared to BFR-LIIT, however, the microvascular
deoxygenation (deoxy-[Hb+Mb]) would be similar between HIIT and BFR-LIIT.
5.2 - Methods
Sixteen healthy, recreationally active subjects participated in the present
investigation and were randomly assigned to a short-term, low volume training program
(HIIT, BFR-LIIT). Each training program consisted of six training sessions completed
over the course of two weeks. Peak aerobic capacity (VO2pk), sub-maximal aerobic
capacity (estimated lactate threshold, time course of oxidative phosphorylation at the
mitochondria) and muscular (knee extensor) strength was assessed pre- and post-training.
The purpose, benefits, and risks associated with participating in the study were explained
and each subject read and voluntarily provided informed consent prior to participating in
any testing. The study was approved by the University of Toledo Institutional Review
Board for the Use of Human Subjects in Research and was carried out in accordance with
the Deceleration of Helsinki. Each subject completed a medical history and physical
activity level questionnaire. Any subject that had previously been diagnosed with a
metabolic, pulmonary, and/or cardiovascular disease, including hypertension, was
67
excluded from the investigation. In addition, any subject that had been diagnosed with
deep vein thrombosis, any blood clotting disorder, and/or an orthopedic-related injury
(within the last 12 months) was also excluded from participation in the investigation.
Each subject was asked to refrain from participating in any strenuous physical activity
throughout the duration of the training investigation, particularly for 24 hours prior to
each data collection session. Each testing and training session was scheduled at
approximately the same time of day for each subject with at least 48 hours between
training sessions and 24 hours between each testing session.
Exercise Testing
During the first session, anthropometric measurements were recorded including
age (years), height (meters, m), weight (kilograms, kg) and resting blood pressure
(mmHg). The subject was seated and remained at rest for five minutes prior to measuring
blood pressure. All blood pressure measurements were obtained with the upper arm
supported at heart level with the subject seated in an upright position. Subjects
demographic data are displayed in Table 1 below.
During the same session, each subject completed a progressive ramp exercise test
to volitional fatigue on a stationary cycle ergometer (Excalibur Sport, Lode, The
Netherlands). The ramp exercise test was progressively increased at an equivalent of 20
watts per minute (W/min). During the progressive ramp exercise test the subjects were
instructed to maintain a pedaling cadence of 80 to 100 revolutions per minute (rpm).
Each subject exercise to volitional fatigue and/or when they could no longer maintain a
pedal cadence above 50 rpm in spite of strong verbal encouragement by the investigators.
Pulmonary gas exchange (oxygen uptake, VO2; carbon dioxide output, VCO2; minute
68
ventilation, VE) was recorded breath by breath using a commercially available metabolic
measurement system (SensorMedics, Vmax, Loma Linda, CA). The metabolic
measurement system was calibrated prior to each testing session according to the
specifications provided by the manufacturer. The flow sensor was calibrated using a 3.0
liter syringe, while the oxygen (O2) and carbon dioxide (CO2) analyzers were calibrated
using reference gases of known concentrations. All pulmonary gas exchange data was
averaged over 10 second bins following the completion of the ramp exercise test and was
used to estimate the lactate threshold (LT) and identify the peak oxygen uptake (VO2pk).
The LT was determined by visual inspection using the V-slope, end-tidal gases, and
ventilatory equivalents as described previously [57, 58]. VO2pk was defined as the
highest VO2 (using the 10 s averaged responses) achieved during the ramp exercise test.
During the second session, each subject completed three maximal knee extensor
strength assessments. The subject was seated on the isokinetic dynamometer (System 2,
Biodex, Shirley, NY) and straps were placed across their torso, hips, thigh and ankle.
The isokinetic dynamometer was calibrated for joint angle, torque and contraction
velocity prior to each session using a two-point calibration process with a known
calibration weight. Next the subject was familiarized with each of the strength
assessment protocols (concentric, eccentric and isometric contractions). The order of the
strength assessment protocols were randomized for each subject during the pre-training
and post-training assessments. During the concentric strength assessment the subject was
asked to forcefully extend their knee as hard as they could throughout their predetermined range of motion. During the eccentric strength assessment the subject was
asked to forcefully resist the isokinetic dynamometer as the knee was forcefully flexed
69
throughout their pre-determined, active range of motion. During each of the isokinetic
strength assessments the contraction velocity was controlled by the isokinetic
dynamometer at 60 °/s, which was similar to the approach used in a previous BFR
investigation examining strength changes subsequent to a cardiovascular training
program [15]. During the isometric strength assessment, the subject's knee joint was
fixed at 90° of flexion as the subject was instructed to forcefully extend their knee as hard
as they could for a 5 second duration, similar to the approach used in a previous
cardiovascular training investigation that utilized BFR [14]. Each subject completed
three attempts of each knee extensor strength assessment with 2-3 minutes of intermittent
recovery in order to avoid fatigue [127].
After the completion of the knee extensor strength assessments, the subjects
recovered for 30 minutes prior to completing the square-wave moderate-intensity
exercise transitions on a cycle ergometer. Each subject performed 6 minutes of exercise
at a work rate of 20 watts (W) which was abruptly transitioned to a work rate equivalent
to 90% of their LT (identified from session one) for 6 minutes. Each subject completed a
total of 6 moderate intensity step transitions on the stationary cycle ergometer during
which pulmonary gas exchange (VO2) was collected using breath-by-breath techniques.
The breath-by-breath response for VO2 was interpolated into 1 second values, smoothed
into 3 second bins, and ensemble averaged during the work rate transition (-120 seconds
to 360 seconds, 0 seconds = work rate transition).
HIIT and BFR-LIIT Interval Training Programs; Protocol and Measurements
At least 96 hours after the second pre-training session, subjects began their
cycling interval training program. Each subject was randomly assigned to complete six
70
exercise sessions of either BFR-LIIT or HIIT on a stationary cycle ergometer within two
weeks. Each exercise session was scheduled for approximately the same time of day and
was separated by 48 - 96 hours. For the purpose of the present investigation an "interval"
was defined as a 75 second low intensity (30 W) bout of exercise followed by a 60
second high intensity bout of exercise. The high exercise intensity used for HIIT was
equivalent to 100% of the subject's peak work rate (WRpk) achieved during the maximal
ramp assessment (session 1), similar to a previous HIIT investigation [7]. As the high
exercise intensity used for the BFR-LIIT program was equivalent to 40% WRpk while
external occlusion was applied bilaterally at the proximal thigh, similar to a previous
BFR cardiovascular investigation [14]. The external occlusion pressure used was
equivalent to 130% of the subject's resting systolic blood pressure (130% SBP), as this
has been a common external occlusion pressure utilized previously during BFR exercise
[14, 15, 36, 42, 53, 101]. The external occlusion pressure was applied by securing an
elastic cuff (Hokanson, SC5, Bellevue, WA, 6.0 cm width) around each of the subject's
proximal thighs. The elastic cuffs was connected to an air compressor and automatic cuff
inflator (Hokanson, E20 Rapid Cuff Inflator, Bellevue, WA) and were immediately
inflated at the onset of exercise and subsequently deflated at the end of exercise. Each
exercise group completed 8 intervals during the first and second exercise sessions, 10
intervals during the third and fourth exercise sessions, and 12 intervals during the fifth
and sixth exercise sessions. The progressive interval design that was used during the
present investigation has been used and discussed previously [7].
During the first exercise training session for each subject, pulmonary VO2,
neuromuscular activation (EMG) of the vastus lateralis and vastus medialis,
71
microvascular oxygenation (NIRS) and rating of perceived exertion (RPE) were recorded
during HIIT and BFR-LIIT. The measurements were made in order to characterize the
exercise training conditions in an attempt to better understand the underlying mechanisms
associated with the previously reported adaptations associated with HIIT and BFR
training programs [8, 14, 15]. In addition, a control group (CON-LIIT) was recruited for
comparative purposes and completed the same exercise protocol as the BFR-LIIT group
but without the bilateral occlusion.
The OMNI scale of perceived exertion was used during the present study to report
RPE. During the present investigation the OMNI scale used the following anchors as "0"
represented "seated rest" and "10" represented "maximal exertion". Each subject
indicated their perceived exertion during the last 10 seconds of each high intensity
interval.
Surface Electromyography (EMG) Techniques
Surface electromyography (EMG) was used to examine the neuromuscular
activation of the vastus lateralis (VL-RMS) and vastus medialis (VM-RMS) during
cycling exercise for each interval exercise condition during the performance of 8
intervals. Prior to placement of the sEMG electrodes, the skin was shaved and cleansed
with an alcohol pad. Double differential EMG electrodes (Delsys, Bagnoli 8-Channel
System, Boston, MA) with a fixed inter-electrode distance of 1 cm were placed on the
vastus lateralis and vastus medialis of the left thigh. The vastus lateralis EMG electrode
was placed at an oblique angle approximately 3-5 cm proximal to the patella just lateral
to the midline over the muscle belly [103]. The vastus medialis EMG electrode was
placed at an oblique angle approximately 2 cm medially from the superior border of the
72
patella within the distal third of the vastus medialis muscle belly [103]. The raw EMG
signal was collected at a sampling frequency of 2,000 Hz using LabChart 7.0
(ADInstruments, Inc., Colorado Springs, CO).
Near-Infrared Spectroscopy (NIRS) Techniques
Frequency-domain multi-distance (FDMD) near-infrared spectroscopy (NIRS) was used
to continuously monitor absolute deoxy-hemoglobin (deoxy-[Hb+Mb]) and oxyhemoglobin (oxy-[Hb+Mb]) responses. Total hemoglobin concentration ([THC]), an
indicator of blood volume within the microvasculature, was calculated as the sum of the
deoxy-[Hb+Mb] and oxy-[Hb+Mb] signals. The NIRS system (Oxiplex TS, ISS,
Champaign, IL) was calibrated prior to each data collection session according to the
specifications provided by the manufacturer and was operated at wavelengths of 690 nm
and 830 nm with a sampling frequency of 50 Hz. It has been previously reported that the
deoxy-[Hb+Mb] signal is less sensitive to blood volume changes (Δ[THC]) compared to
the oxy-[Hb+Mb] signal [104] and that deoxy-[Hb+Mb] can be used as an estimation of
oxygen extraction [105, 106]. Although the microvascular deoxygenation response
within the vastus lateralis has been shown to be non-uniform throughout the muscle
during fatiguing exercise, the greatest microvascular deoxygenation response has been
observed at the middle region of the vastus lateralis during knee extension exercise
compared to the distal regions [107]. Therefore, the NIRS sensor was positioned midway
between the ASIS and the superior border of the patella over the muscle belly of the
vastus lateralis in the present investigation. Prior to placement of the NIRS sensor the
skin was shaved and cleansed with an alcohol pad in order to improve the signal quality
[128]. The NIRS sensor was covered with a dark black cloth, in order to prevent stray
73
visible light sources from affecting the data acquisition, and secured with straps around
the thigh.
Data Processing
EMG responses for the vastus lateralis and vastus medialis were normalized to the
average neuromuscular activation recorded during three maximal voluntary isometric
contractions (5 seconds, MVIC) and are presented as a percentage of MVIC (%MVIC).
In order to obtain an overall representation of neuromuscular activation the vastus
lateralis and vastus medialis responses were averaged (AVG-RMS), as described
previously [120, 129].
All exercising deoxy-[Hb+Mb] data collected during the acute interval sessions
were smoothed by a moving average into 1 second bins and represented as a percentage
change from baseline (%BL). The baseline values for deoxy-[Hb+Mb] were obtained
during the last 15 seconds of the first low intensity interval (30W) prior to the first work
rate transition. EMG was assessed during the last 15 seconds of each high intensity
interval, while deoxy-[Hb+Mb] and VO2 were assessed during the last 15 seconds of each
low intensity (30W) and high intensity (100%WRpk, 40%WRpk) interval. All RPE scores
obtained for each of the 8 intervals were averaged and presented as mean RPE.
For each on-transition to moderate intensity exercise (i.e. 90% LT), the breath-bybreath data were linearly interpolated to 1 s values, smoothed using a 3 s moving average,
time aligned to the onset of exercise and ensemble averaged to provide a single ontransition for each subject. The time course of VO2 after the onset of exercise was
described for each subject using a model that provides an estimate of the baseline (BL),
amplitudes (A1, A2), time delays (TD2) and time constants (τ1, τ2) [130]. Model
74
parameters were determined using least-squares non-linear regression in which the
convergence criteria were satisfied by minimizing the sum of squared errors. The first
exponential term begins coincident with the onset of exercise (i.e. no time delay) while
the exponential terms describing the primary component begins after an independent time
delay (TD2). The parameter estimates for the on-transient were determined as a function
of time (t) using a two-component exponential model,
VO2(t) = VO2(BL) + A1  (1-e-t/τ1) + A2  (1-e-(t-TD2)/ τ 2)
In this model, the exponential term describing phase I is primarily descriptive up to the
value of TD2. The physiologically relevant response is τ2 which reflects the time course
for oxidative phosphorylation at the level of the mitochondria [61, 130, 131].
Statistical Analysis
Two-way (exercise condition x time) analysis of variance (ANOVA) with one
repeated measure was used to identify differences in VO2pk, LT, τVO2, peak isometric
strength, peak concentric strength and peak eccentric strength subsequent to each of the
training programs (BFR-LIIT and HIIT). Furthermore, an independent t-test was utilized
to identify any differences between training programs (BFR-LIIT and HIIT) in the
percent change from pre-training (%ΔPRE) within VO2pk, LT, τVO2, peak isometric
strength, peak concentric strength and peak eccentric strength.
Two-way (exercise condition x interval) ANOVA with one repeated measure was
used to identify differences in exercising EMG (%MVIC), VO2 (mL/kg/min) and deoxy[Hb+Mb] (%BL) during the acute exercise session. While a one-way (exercise
condition) ANOVA was used to identify differences in the group mean RPE response
during the acute exercise session. Tukey's post-hoc analysis was used in order to find
75
significance when appropriate. Statistical significance was set priori at p ≤ 0.05. All
values are expressed as mean ± standard deviation (SD). All statistical analysis was
completed using Sigma Stat software (Sigma Stat 3.5, Systat Software, San Jose, CA).
5.3 - Results
HIIT and BFR-LIIT Training Results
All training outcomes are described in table 5-2 (below) as percent changes from
pre-training (%ΔPRE). A main effect for VO2pk was detected with post-training VO2pk (
38.7 ± 7.7 mL/kg/min) being greater than pre-training VO2pk ( 36.8 ± 6.8 mL/kg/min, p =
0.001). Furthermore, HIIT elicited a 6.5% increase in VO2pk from pre-training ( 37.9 ±
6.7 mL/kg/min) to post-training (40.6 ± 8.5 mL/kg/min, p = 0.001), however, no
difference (3.3%) in VO2pk was found between pre- and post-training in the BFR-LIIT
programs (Figure 5.1).
A comparison of the estimated LT, expressed as VO2 responses indicated a main
effect of time in which post-training (22.7 ± 4.6 mL/kg/min) was greater than pre-training
(19.8 ± 4.0, p = 0.005). In addition, BFR-LIIT resulted in a 20.4% increase in LT from
pre-training (18.8 ± 3.4 mL/kg/min) to post-training (22.6 ± 5.1 mL/kg/min, p = 0.009)
while no difference (11.5%) in LT was observed following HIIT (Figure 5.2).
The τVO2 for phase II kinetics exhibited a main effect of time as pre-training time
constants were slower (34.1 ± 15.2 seconds) compared to post-training values (27.1 ±
11.7 seconds, p = 0.05). Furthermore, HIIT speed the phase II τVO2 as post-training
values (23.7 ± 10.7 seconds) were 28.1% less than pre-training values (35.3 ± 16.4
seconds, p = 0.008), however, no change (3.1%) in the phase II τVO2 was observed
following BFR-LIIT (Figure 5.3).
76
No significant differences were detected in peak concentric strength within either
training condition subsequent to BFR-LIIT or HIIT (Figure 5.4). Peak eccentric strength
increased 9.5% from pre-training (224.0 ± 76.7 Nm) to post-training (244.7 ± 76.7 Nm, p
= 0.029) subsequent to BFR-LIIT. While significant decreases (10.2%) in peak eccentric
strength (Pre = 260.3 ± 69.1 Nm; Post = 235.1 ± 69.1 Nm; p = 0.007) were detected
following HIIT (Figure 5.4).
Finally, peak isometric strength increased 12.2% following BFR-LIIT (Pre =
50.1± 13.4 kg; Post = 56.9 ± 18.5 kg; p = 0.012) while no significant changes (2.2%)
were detected subsequent to HIIT (Figure 5.5).
Acute Interval Exercise Results
Exercising VO2 was greater during HIIT compared to BFR-LIIT and CON-LIIT
during the high intensity work rates of all eight intervals (p < 0.001, Figure 5.6), while no
significant differences in exercising VO2 were detected between BFR-LIIT and CONLIIT. Exercising VO2 was also greater during HIIT compared to BFR-LIIT during the
low intensity work rates of intervals 3-8 (Figure 5.6). In addition, HIIT elicited greater
exercising VO2 compared to CON-LIIT during the low intensity work rates of intervals 4
and 7 (Figure 5.6). Similar to the high intensity work rates, no significant differences in
exercising VO2 were detected between BFR-LIIT and CON-LIIT during any of the low
intensity work rates for any of the intervals.
HIIT elicited greater deoxy-[Hb+Mb] compared to BFR-LIIT during all of the
high intensity work rates of all eight intervals (Figure 5.7). Furthermore, greater deoxy[Hb+Mb] was detected for HIIT compared to CON-LIIT during the high intensity work
rates of intervals 2-8 (Figure 5.7). Deoxy-[Hb+Mb] was also greater for HIIT compared
77
to BFR-LIIT during the low intensity work rates of intervals 4, 5, 6, and 8 (Figure 5.7).
Furthermore, deoxy-[Hb+Mb] was greater for HIIT compared to CON-LIIT during the
low intensity work rates of intervals 4 and 5 (Figure 5.7). No significant differences in
deoxy-[Hb+Mb] were detected between BFR-LIIT and CON-LIIT during any of the high
intensity or low intensity work rates for any interval (Figure 5.7).
HIIT elicited greater neuromuscular activation (AVG-RMS) compare to both
BFR-LIIT and CON-LIIT during the high intensity work rates of intervals 2 - 7 (Figure
5.8). No significant differences in neuromuscular activation (AVG-RMS) were observed
between BFR-LIIT and CON-LIIT for any of the high intensity work rates during all
eight intervals (Figure 5.8).
Lastly, the group mean RPE was significantly greater during HIIT (7.4 ± 0.8)
compared to both BFR-LIIT (4.0 ± 1.3, p < 0.001) and CON-LIIT (3.3 ± 0.8, p < 0.001).
However no significant difference in mean RPE was observed between BFR-LIIT or
CON-LIIT (Figure 5.9).
5.4 - Discussion
Contrary to our primary hypothesis short-term (two weeks) BFR-LIIT did not
significantly increase VO2pk (Figure 5.1) or speed the phase II τVO2 (Figure 5.3). The
present results are similar to a previous investigation that did not observe any changes in
VO2pk following six weeks (3 days/week) of BFR interval training [132]. Despite similar
findings, the previous investigation [132] and the present investigation had different
exercise protocols (i.e., exercise intensity, exercise bout duration, cuffing procedure).
However, short (15 minutes), continuous, low intensity (40%VO2pk) BFR cycle training
has been reported to increase VO2pk after six weeks (3 days/week) of training [14]. The
78
exercise intensity and cuffing procedure of the present investigation were similar to the
continuous BFR cycling investigation [14], however, the present investigation did not
yield any substantial changes in the VO2pk subsequent to training. Therefore, it could be
suggested that a continuous exercise bout is an important training stimulus as exercise
bout durations were similar between the two investigations (continuous BFR cycle = 15
minutes [14], BFR-LIIT = 8-12 minutes). Furthermore, the intermittent exercise protocol
used in the present investigation allowed for the exercising VO2 (Figure 5.6) and deoxy[Hb-Mb] (Figure 5.7) to recover during the low intensity work rates of each interval,
whereas the continuous BFR cycling protocol of the previous investigation [14] may not
have allowed for the same recovery (Chapter 4, [133]).
The present investigation also observed significant increases in the estimated
lactate threshold (LT) subsequent to BFR-LIIT (Figure 5.2). This would suggest a right
shift in the LT and a greater sub-maximal work capacity subsequent to training [29].
However, the post-training estimated LT was not significantly different between training
groups and when presented as a percent change from pre-training (%ΔPRE), there was no
significant difference observed between BFR-LIIT (20.4%) and HIIT (11.5%). Further
investigation is required to help explain how the estimated LT is affected following BFR
training (both cardiovascular and resistance) as increases in sub-maximal endurance has
been previously demonstrated following BFR knee extension training [134].
The present investigation demonstrated similar training outcomes as previous
investigations [8, 56] as VO2pk increased and the phase II τVO2 sped subsequent to shortterm (two weeks) HIIT. The 6.5% increase in VO2pk observed during the present
investigation is similar to a previous investigation reporting a ~7% increase in VO2pk
79
following two weeks of HIIT [56]. However, unlike previous investigations [8, 56] no
significant increase in estimated LT was observed subsequent to HIIT during the present
investigation. This finding may have been due to the exercise intensity (100% WRpk)
used during the present investigation, as previous investigations [8, 56] used
supramaximal exercise intensities (110% WRpk) during their training protocols.
However, this observation requires further investigation into the effects of LT subsequent
to short-term HIIT.
In agreement with our hypothesis, no changes in peak isometric or peak
concentric knee extensor strength were observed following HIIT, however, a significant
decline in peak eccentric knee extensor strength was detected (Figures 5.4, 5.5).
Declining strength has been previously associated with the later stages of a
cardiovascular training program [135]. This decline in strength may be due to the
interaction between the activation of adenosine monophosphate activated protein kinase
(AMPK) and the suppression of mammalian target of rapamycin (mTOR) [136].
However, HIIT has been previously shown to increase skeletal muscle strength at slow
contraction velocities (30 °/s, 60 °/s, 120 °/s) [137]. Initial increases in skeletal muscle
strength have been associated with neuromuscular adaptations rather than protein
synthesis and skeletal muscle hypertrophy [127], therefore investigation into the potential
neuromuscular adaptations related to skeletal muscle strength subsequent to short-term
HIIT are necessary.
Despite the lack of strength adaptations associated with HIIT, the present
investigation did report significant increases in peak isometric and peak eccentric
strength subsequent to BFR-LIIT (Figures 5.4, 5.5). Peak isometric strength has been
80
previously reported to increase following six weeks of low-intensity (40% WRpk),
continuous BFR cycle training [14]. However, the finding of increased peak eccentric
strength after short-term BFR-LIIT is novel to the present investigation. The increased
peak eccentric strength could be due to the eccentric component previously reported to be
associated with BFR exercise [109]. The relatively rapid (two weeks) strength increases
reported during the present investigations and previously following BFR cardiovascular
exercise programs [13, 14] could be due to neuromuscular adaptations [127], however the
authors of the present investigation can only speculate and further investigation is
required. During an acute interval session, no significant difference in neuromuscular
activation (AVG-RMS) was detected between BFR-LIIT and CON-LIIT. Furthermore,
HIIT resulted in greater neuromuscular activation (AVG-RMS) compared to BFR-LIIT
(Figure 5.8). Despite only being able to speculate the mechanism responsible for the
strength adaptations subsequent to BFR-LIIT, the present investigation did report a
relatively lower amount of exertion during BFR-LIIT (4.0 ± 1.3), compared to HIIT (7.4
± 0.8), that elicited significant increases in muscle strength.
5.5 - Conclusion
In conclusion, according to the results of the present investigation acute (two
weeks) BFR-LIIT does not elicit similar cardiovascular training adaptations as acute
HIIT. However, significant increases in knee extensor strength and possible increases in
estimated LT was detected following BFR-LIIT. Future investigations should determine
the relationship between BFR cardiovascular exercise as a potential model of concurrent
training. According to the results of the present investigation, it could be suggested that
much consideration should be given to the prescribed exercise volume (continuous vs.
81
interval) as it appears to be a vital training stimulus during the performance of BFR
cardiovascular exercise. This may explain the lack of cardiovascular training adaptations
reported while using a low volume cardiovascular training modes (i.e., interval), such as
the one used in the present investigation.
82
Figure 5-1 Peak oxygen uptake (VO2pk) increased subsequent to two weeks (6 exercise
sessions) of high-intensity interval training (HIIT, red triangles). *Significantly different
from "pre-training" within the same exercise condition (p ≤ 0.05).
83
Figure 5-2 Estimated lactate threshold increased following two weeks (6 sessions) of
blood flow restricted low-intensity interval training (BFR-LIIT, black circles).
*Significantly different from "pre-training" within the same exercise condition (p ≤ 0.05).
84
Figure 5-3 Two weeks (6 sessions) of high-intensity interval training (HIIT, red
triangles) resulted in a decrease of the time constant for phase II oxygen uptake kinetics
(τVO2) during moderate-intensity work rate transitions. *Significantly different from
"pre-training" within the same exercise condition (p ≤ 0.05).
85
Figure 5-4 No significant differences in peak concentric strength were observed
following either training program. *Significantly different from "pre-training" within the
same exercise condition (p ≤ 0.05).
86
Figure 5-5 Blood flow restriction low-intensity interval training (BFR-LIIT, black
circles) elicited a significant increase in peak eccentric knee extensor torque following a
two week (6 sessions) training program. Peak eccentric knee extensor torque decreased
subsequent to two weeks (6 sessions) of high-intensity interval training (HIIT, red
triangles). *Significantly different from "pre-training" within the same exercise condition
(p ≤ 0.05).
87
Figure 5-6 Peak isometric strength increased following two weeks (6 sessions) of blood
flow restricted low-intensity interval training (BFR-LIIT, black circles). *Significantly
different from "pre-training" within the same exercise condition (p ≤ 0.05).
88
Figure 5-7 High-intensity interval training (HIIT, green triangles) elicited a higher
oxygen uptake (VO2) during the high portion (H) and low portion (L) of the intervals
compared to blood flow restricted low-intensity interval training (BFR-LIIT, red circles)
and control low-intensity interval training (CON-LIIT, black circles). *Significantly
different from CON-LIIT, p ≤ 0.05. +Significantly different from BFR-LIIT, p ≤ 0.05.
89
Figure 5-8 High-intensity interval training (HIIT, green triangles) elicited a higher
microvascular deoxygenation (deoxy-[Hb+Mb]) during the high portion (H) and low
portion (L) of the intervals compared to blood flow restricted low-intensity interval
training (BFR-LIIT, red circles) and control low-intensity interval training (CON-LIIT,
black circles). *Significantly different from CON-LIIT, p ≤ 0.05. +Significantly
different from BFR-LIIT, p ≤ 0.05.
90
Figure 5-9 No significant difference in total hemoglobin concentration ([THC]) between
conditions during either the high portions (H) or low portions (L) of the intervals.
*Significantly different from CON-LIIT, p ≤ 0.05. +Significantly different from BFRLIIT, p ≤ 0.05.
91
Figure 5-10 High intensity interval training (HIIT, green bars) resulted in greater
neuromuscular activation (AVG-RMS) during the high portion of the last seven intervals
compared to blood flow restriction low-intensity interval training (BFR-LIIT, red bars) or
control low-intensity interval training (CON-LIIT, black bars). *Significantly different
from CON-LIIT, p ≤ 0.05. +Significantly different from BFR-LIIT, p ≤ 0.05.
92
Figure 5-11 High-intensity interval training (HIIT, green bar) elicited higher mean
ratings of perceived exertion (RPE) during the completion of eight intervals compared to
blood flow restriction low-intensity interval training (BFR-LIIT, red bar) or control lowintensity interval training (CON-LIIT, black bar). *Significantly different from CONLIIT, p ≤ 0.05. +Significantly different from BFR-LIIT, p ≤ 0.05.
93
Table 5.1 Subject Demographics
BFR-LIIT Group
Gender
Age (yrs)
HIIT Group
CON-LIIT Group
5 Males / 3 Females 5 Males / 3 Females 6 Males / 2 Females
28 ± 6
30 ± 5
24 ± 4
Height (m)
1.74 ± 0.09
1.77 ± 0.12
1.74 ± 0.10
Weight (kg)
79.9 ± 13.5
83.5 ± 19.0
81.0 ± 14.8
Absolute Peak
Oxygen Uptake
(ml/min)
2871 ± 767
3108 ± 645
3655 ± 964
Relative Peak
Oxygen Uptake
(ml/kg/min)
35.7 ± 6.9
37.9 ± 6.7
44.8 ± 7.3
Resting Systolic
Blood Pressure
(mmHg)
124 ± 9
123 ± 8
121 ± 9
Resting Diastolic
Blood Pressure
(mmHg)
80 ± 3
80 ± 3
81 ± 3
94
Table 5.2 Training Adaptations: Percent Change from Pre-Training (%ΔPRE)
BFR-LIIT Group
HIIT Group
VO2pk (mL/kg/min)
3.3%
6.5%
(0.9%, 5.7%)
(1.3%, 11.7%)
Estimated LT
20.4%
11.5%
(mL/kg/min)
(4.2%, 36.6%)
(-2.3%, 25.2%)
Phase II τVO2 (sec)
3.1%
-28.1%
(-37.2%, 43.3%)
(-47.1%, -9.2%)
CONpk (Nm)
-3.4%
-12.7%
(-10.9%, 4.1%)
(-31.2%, 5.8%)
ECCpk (Nm)
9.5%
-10.2%*
(-0.2%, 19.3%)
(-18.0%, -2.3%)
ISOpk (Kg)
12.2%
2.2%
(0.7% 23.6%)
(-7.6%, 12.1%)
All data presented as group mean of the percent change from pre-training (%ΔPRE) and
95% confidence intervals. Percent change in peak eccentric knee extensor strength
(ECCpk) was significantly lower during high-intensity interval training (HIIT) compared
to blood flow restriction low-intensity interval training (BFR-LIIT). *Significantly
different from blood flow restriction low-intensity interval training (BFR-LIIT), p ≤ 0.05.
95
Chapter 6
Conclusion
It was the primary purpose of this dissertation to discuss the acute (one exercise
session) and training (two weeks) responses of blood flow restriction (BFR)
cardiovascular exercise. Chapter 3 demonstrated that occlusion duration does impact
oxygen extraction within the microvasculature (deoxy-[Hb+Mb]) only during the
performance of low-intensity isometric exercise despite no significant change in
neuromuscular activation. BFR also elicited increased oxygen extraction during constant
load cycling compared to free flow (control) cycling (Chapter 4). However, despite the
increased oxygen extraction pulmonary oxygen uptake (VO2) was not affected. These
results suggest that the perturbation caused by BFR may have a greater localized effect
within the exercising musculature compared to the rest of the body.
When implementing BFR into a cardiovascular exercise program, exercise
volume should be a major consideration. By lowering the exercise intensity, commonly
done when performing BFR exercise, one is putting greater emphasis on exercise volume.
A pattern (although not significant) emerged from the VO2 and deoxy-[Hb+Mb] data
while performing one session of BFR low-intensity interval exercise that suggested even
though the occlusion remained applied during the low-intensity portion of the intervals
96
the subject was still able to recover (Chapter 5). This finding suggests that BFR
techniques did not provide any additional metabolic stress possibly due to the lower
exercise volume induced by the interval exercise model. The lack of metabolic stress
stimulus and relatively short training program (2 weeks) may help to explain the lack of
increase in peak aerobic capacity (3.3%, VO2pk) following BFR low-intensity interval
training (BFR-LIIT, Chapter 5).
In conclusion, the findings within this dissertation would not recommend the use
of BFR during low volume (interval) exercise programs if the training objectives are
cardiovascular adaptations. However, BFR-LIIT did show an improvement in submaximal aerobic capacity subsequent to training. This finding should be further
investigated as to how well these training adaptations apply to more functional tasks (i.e.,
activities of daily living, muscular endurance) in a variety of populations. Furthermore,
BFR-LIIT did rapidly improve knee extensor strength subsequent to a two week training
program. Although the exact mechanism(s) responsible for the increase in strength are
currently unknown at this time and require further investigation it could be suggested,
due to the rapid strength improvements, that these findings are due to neuromuscular
adaptations. Future research investigations are required to provide more evidence for the
potential mechanism(s) responsible. Overall, it would not be recommended to use BFR
interval training if increasing peak aerobic capacity is the primary training goal.
97
References
1.
Ehrman, J., et al., eds. ACSM's Resource Manual for Guidelines for Exercise
Testing and Prescription. 6 ed. 2010, Lippincott Williams & Wilkins: Baltimore,
MD. 868.
2.
Go, A., et al., Heart disease and stroke statistics - 2014 update: a report from the
american heart association. Circulation, 2014. 128.
3.
Warburton, D., C. Nicol, and S. Bredin, Health benefits of physical activity: the
evidence. CMAJ, 2006. 174: p. 801-809.
4.
Hawley, J., Exercise as a therapeutic intervention for the prevention and
treatment of insulin resistance. Diabetes Metab Res Rev, 2004. 20: p. 383-393.
5.
Godin, G., et al., Differences in perceived barriers to exercise between high and
low intenders: observations among different populations. Am J Health Promotion,
1994. 8: p. 279-284.
6.
Trost, S., et al., Correlates of adults' participation in physical activity: review and
update. Med Sci Sports Exerc, 2002. 34: p. 1996-2001.
7.
Little, J., et al., A practical model of low-volume high-intensity interval training
induces mitochondrial biogenesis in human skeletal muscle: potential
mechanisms. J Physiol, 2010. 588: p. 1011-1022.
98
8.
McKay, B., D. Paterson, and J. Kowalchuk, Effect of short-term high-intensity
interval training vs. continuous training on O2 uptake kinetics, muscle
deoxygenation, and exercise performance. J Appl Physiol, 2009. 107: p. 128-138.
9.
Burgomaster, K., et al., Similar metabolic adaptations during exercise after low
volume sprint interval and traditional endurance training in humans. J Physiol,
2008. 586: p. 151-160.
10.
Rodas, G., et al., A short training programme for the rapid improvement of both
aerobic and anaerobic metabolism. Eur J Appl Physiol, 2000. 82: p. 480-486.
11.
Helgerud, J., et al., Aerobic high-intensity interval improve VO2max more than
moderate training. Med Sci Sports Exerc, 2007. 39: p. 665-671.
12.
Talanian, J., et al., Two weeks of high-intensity aerobic interval training increases
the capacity for fat oxidation during exercise in women. J Appl Physiol, 2007.
102: p. 1439-1447.
13.
Abe, T., C. Kearns, and Y. Sato, Muscle size and strength are increased following
walk training with restricted venous blood flow from the leg muscle, Kaatsu-walk
training. J Appl Physiol, 2006. 100: p. 1460-1466.
14.
Abe, T., et al., Effects of low-intensity cycle training with restricted leg blood flow
on thigh muscle volume and VO2max in young men. Journal of Sports Science and
Medicine, 2010. 9: p. 452-458.
15.
Park, S., et al., Increase in maximal oxygen uptake following 2-week walk training
with blood flow occlusion in athletes. Eur J Appl Physiol, 2010. 109: p. 591-600.
16.
Takarada, Y., et al., Rapid increase in plasma growth hormone after low-intensity
resistance exercise with vascular occlusion. J Appl Physiol, 2000. 88: p. 61-65.
99
17.
Takarada, Y., et al., Effects of resistance exercise combined with moderate
vascular occlusion on muscular function in humans. J Appl Physiol, 2000. 88: p.
2097-2106.
18.
Yasuda, T., et al., Effects of low-intensity, elastic band resistance exercise
combined with blood flow restriction on muscle activation. Scand J Med Sci
Sports, 2014. 24: p. 55-61.
19.
Moritani, T., et al., Oxygen availability and motor unit activity in humans. Eur J
Appl Physiol, 1992. 64: p. 552-556.
20.
Kaijser, L., et al., Muscle oxidative capacity and work performance after training
under local leg ischemia. J Appl Physiol, 1990. 69: p. 785-787.
21.
Sundberg, C., et al., Effects of ischaemic training on local aerobic muscle
performance in man. Acta Physiol Scand, 1993. 148: p. 13-19.
22.
Norrbom, J., et al., PGC-1α mRNA expression is influenced by metabolic
perturbation in exercising human skeletal muscle. J Appl Physiol, 2004. 96: p.
189-194.
23.
Esbjornsson, M., et al., Muscle fibre types and enzyme activities after training
with local leg ischaemia in man. Acta Physiol Scand, 1993. 148: p. 233-241.
24.
Wasserman, K., et al., Principles of Exercise Testing and Interpretation Including
Pathophysiology and Clinical Applications. 3rd ed. 1999, Philadelphia, PA:
Lippincott Williams & Wilkins. 556.
25.
Keteyian, S., et al., Peak aerobic capacity predicts prognosis in patients with
coronary heart disease. Am Heart J, 2008. 156: p. 292-300.
100
26.
Henriksson, J. and J. Reitman, Time course of changes in human skeletal muscle
succinate dehydrogenase and cytochrome oxidase activities and maximal oxygen
uptake with physical activity and inactivity. Acta Physiologica Scandinavica,
1977. 99: p. 91-97.
27.
Laursen, P. and D. Jenkins, The scientific basis for high-intensity interval
training: optimising training programmes and maximising performance in highly
trained endurance athletes. Sports Med, 2002. 32: p. 53-73.
28.
Gibala, M. and S. McGee, Metabolic adaptations to short-term high-intensity
interval training: a little pain for a lot of gain? Exerc Sport Sci Rev, 2008. 36: p.
58-63.
29.
Brooks, G., T. Fahey, and K. Baldwin, Exercise Physiology: Human
Bioenergetics and Its Applications. 4 ed. 2005, New York, NY: McGraw-Hill.
30.
Leek, B., et al., Effect of acute exercise on citrate synthase activity in untrained
and trained human skeletal muscle. Am J Physiol Regul Integr Comp Physiol,
2001. 280: p. R441-R447.
31.
Austin, S. and J. St-Pierre, PGC1alpha and mitochondrial metabolism - emerging
concepts and relevance in ageing and neurodegenerative disorders. Journal of
Cell Science, 2012. 125: p. 4963-4971.
32.
Hock, M. and A. Kralli, Transcriptional control of mitochondrial biogenesis and
function. Annu Rev Physiol, 2009. 71: p. 177-203.
33.
Little, J., et al., Acute endurance exercise increases the nuclear abundance of
PGC-1a in trained human skeletal muscle. Am J Physiol Regul Integr Comp
Physiol, 2010. 298: p. R912-R917.
101
34.
Takada, S., et al., Low-intensity exercise can increase muscle mass and strength
proportionally to enhanced metabolic stress under ischemic conditions. J Appl
Physiol, 2012. 113: p. 199-205.
35.
Suga, T., et al., Effect of multiple set on intramuscular metabolic stress during
low-intensity resistance exercise with blood flow restriction. Eur J Appl Physiol,
2012. 112: p. 3915-3920.
36.
Suga, T., et al., Dose effect on intramuscular metabolic stress during low-intensity
resistance exercise with blood flow restriction. J Appl Physiol, 2010. 108: p.
1563-1567.
37.
Abe, T., et al., Skeletal muscle size and circulating IGF-1 are increased after two
weeks of twice daily "KAATSU" resistance training. Int J Kaatsu Training Res,
2005. 1: p. 6-12.
38.
Fry, C., et al., Blood flow restriction exercise stimulates mTORC1 signaling and
muscle protein synthesis in older men. J Appl Physiol, 2010. 108: p. 1199-1209.
39.
Fujita, S., et al., Blood flow restriction during low-intensity resistance exercise
increases S6K1 phosphorylation and muscle protein synthesis. J Appl Physiol,
2007. 103: p. 903-910.
40.
Shinohara, M., et al., Efficacy of tourniquet ischemia for strength training with
low resistance. Eur J Appl Physiol, 1998. 77: p. 189-191.
41.
Yasuda, T., et al., Muscle fiber cross-sectional area is increased after two weeks
of twice daily KAATSU-resistance training. Int. J. Kaatsu Training Res., 2005. 1:
p. 65-70.
102
42.
Yasuda, T., et al., Combined effects of low-intensity blood flow restriction
training and high-intensity resistance training on muscle strength and size. Eur J
Appl Physiol, 2011. 111: p. 2525-2533.
43.
Larkin, K., et al., Blood flow restriction enhances post-resistance exercise
angiogenic gene expression. Med Sci Sports Exerc, 2012. 44: p. 2077-2083.
44.
Ozaki, H., et al., Effects of 10 weeks walk training with leg blood flow reduction
on carotid arterial compliance and muscle size in the elderly adults. Angiology,
2011. 62: p. 81-86.
45.
Ozaki, H., et al., Metabolic and cardiovascular responses to upright cycle
exercise with leg blood flow reduction. Journal of Sports Science and Medicine,
2010. 9: p. 224-230.
46.
Iida, H., et al., Effects of walking with blood flow restriction on limb venous
compliance in elderly subjects. Clin Physiol Funct Imaging, 2011. 31: p. 472-476.
47.
Abe, T., et al., Effects of low-intensity walk training with restricted leg blood flow
on muscle strength and aerobic capacity in older adults. J Geriatr Phys Ther,
2010. 33: p. 34-40.
48.
Richardson, R., et al., Exercise adaptation attenuates VEGF gene expression in
human skeletal muscle. Am J Physiol Heart Circ Physiol, 2000. 279: p. H772H778.
49.
Gustafsson, T. and W. Kraus, Exercise-induced angiogenesis-related growth and
transcription factors in skeletal muscle, and their modification in muscle
pathology. Front Biosci, 2001. 6: p. 75-89.
103
50.
Anderson, P. and J. Hendricksson, Capillary supply of the quadriceps femoris
muscle of man: adaptive response to exercise. J. Physiol. (Lond.), 1977. 270: p.
677-690.
51.
Bebout, D., et al., Effects of training and immobilization on VO2 and DO2 in dog
gastrocnemius muscle in situ. J. Appl. Physiol., 1993. 74: p. 1697-1703.
52.
Brodal, P., F. Ingjer, and L. Hermansen, Capillary supply of skeletal muscle fibers
in untrained and endurance-trained men. Am J Physiol Heart Circ Physiol, 1977.
232: p. H705-H712.
53.
Takano, H., et al., Hemodynamic and hormonal responses to a short-term lowintensity resistance exercise with the reduction of muscle blood flow. Eur J Appl
Physiol, 2005. 95: p. 65-73.
54.
Gustafsson, T., et al., Exercise-induced expression of angiogenesis-related
transcription and growth factors in human skeletal muscle. Am J Physiol Heart
Circ Physiol, 1999. 276: p. H679-H685.
55.
Terrados, N., et al., Is hypoxia a stimulus for synthesis of oxidative enzymes and
myoglobin? J Appl Physiol, 1990. 68: p. 2369-2372.
56.
Williams, A., D. Paterson, and J. Kowalchuk, High-intensity interval training
speeds the adjustment of pulmonary O2 uptake, but not muscle deoxygenation,
during moderate-intensity exercise transitions initiated from low and elevated
baseline metabolic rates. J Appl Physiol, 2013. 114: p. 1550-1562.
57.
Wasserman, K., et al., Anaerobic threshold and respiratory gas exchange during
exercise. J Appl Physiol, 1973. 35: p. 236-243.
104
58.
Beaver, W., K. Wasserman, and B. Whipp, A new method for detecting anaerobic
threshold by gas exchange. J Appl Physiol, 1986. 60: p. 2020-2027.
59.
Whipp, B., et al., Parameters of ventilatory and gas exchange dynamics during
exercise. J Appl Physiol, 1982. 52: p. 1506-1513.
60.
Barstow, T., N. Lamarra, and B. Whipp, Modulation of muscle and pulmonary O2
uptakes by circulatory dynamics during exercise. J Appl Physiol, 1990. 68: p.
979-989.
61.
Grassi, B., et al., Muscle O2 uptake kinetics in humans: implications for
metabolic control. J Appl Physiol, 1996. 80: p. 988-998.
62.
Berger, N., et al., Influence of continuous and interval training on oxygen uptake
on-kinetics. Med Sci Sports Exerc, 2006. 38: p. 504-512.
63.
Phillips, S., et al., Progressive effect of endurance training on VO2 kinetics at the
onset of submaximal exercise. J Appl Physiol, 1995. 79: p. 1914-1920.
64.
Burgomaster, K., G. Heigenhauser, and M. Gibala, Effect of short-term sprint
interval training on human skeletal muscle carbohydrate metabolism during
exercise and time-trial performance. J Appl Physiol, 2006. 100: p. 2041-2047.
65.
Bucheit, M., et al., Performance and physiological responses during a sprint
interval training session: relationships with muscle oxygenation and pulmonary
oxygen uptake kinetics. Eur J Appl Physiol, 2012. 112: p. 767-779.
66.
Slordahl, S., et al., Atrioventricular plane displacement in untrained and trained
females. Med Sci Sports Exerc, 2004. 36: p. 1871-1875.
105
67.
Warburton, D., et al., Effectiveness of high-intensity interval training for the
rehabilitation of patients with coronary artery disease. Am J Cardiol, 2005. 95: p.
1080-1084.
68.
Wisloff, U., et al., Superior cardiovascular effect of aerobic interval training
versus moderate continuous training in heart failure patients a randomized study.
Circulation, 2007. 115: p. 3086-3094.
69.
Nytroen, K., et al., High-intensity interval training improves peak oxygen uptake
and muscular exercise capacity in heart transplant recipients. American Journal
of Transplantation, 2012. 12: p. 3134-3142.
70.
Gormley, S., et al., Effect of intensity of aerobic training on VO2max. Med Sci
Sports Exerc, 2008. 40: p. 1336-1343.
71.
Gibala, M., et al., Short-term sprint interval versus traditional endurance
training: similar initial adaptations in human skeletal muscle and exercise
performance. J Physiol, 2006. 575: p. 901-911.
72.
Prieur, F. and P. Mucci, Effect of high-intensity interval training on the profile of
muscle deoxygenation heterogeneity during incremental exercise. Eur J Appl
Physiol, 2013. 113: p. 249-257.
73.
Turner, A., et al., Oxygen uptake and muscle desaturation kinetics during
intermittent cycling. Med Sci Sports Exerc, 2006. 38: p. 492-503.
74.
Ratamess, N., et al., Progression Models in Resistance Training for Healthy
Adults, in Special Communications: Position Stand 2009, American College of
Sports Medicine: Medicine and Science in Sports and Exercise. p. 687-708.
106
75.
McDonagh, M. and C. Davies, Adaptive response of mammalian skeletal muscle
to exercise with high loads. Eur J Appl Physiol, 1984. 52: p. 139-155.
76.
Eiken, O. and H. Bjurstedt, Dynamic exercise in man as influenced by
experimental restriction of blood flow in the working muscles. Acta Physiol
Scand, 1987. 131: p. 339-345.
77.
Yoshida, T., et al., Effect of hypoxia on arterial and venous blood levels of
oxygen, carbon dioxide, hydrogen ions and lactate during incremental forearm
exercise. Eur J Appl Physiol, 1989. 58: p. 772-777.
78.
Annex, B., et al., Induction and maintenance of increased VEGF protein by
chronic motor nerve stimulation in skeletal muscle. Am J Physiol Heart Circ
Physiol, 1998. 274: p. H860-H867.
79.
Skorjanc, D., et al., Sequential increases in capillarization and mitochondrial
enzymes in low-frequency-stimulated rabbit muscle. Am J Physiol Cell Physiol,
1998. 274: p. C810-C818.
80.
Loenneke, J., et al., The anabolic benefits of venous blood flow restriction
training may be induced by muscle cell swelling. Med Hypotheses, 2012. 78: p.
151-154.
81.
Sundberg, C. and L. Kaijser, Effects of graded restriction of perfusion on
circulation and metabolism in the working leg: quantification of a human
ischaemia-model. Acta Physiol Scand, 1992. 146: p. 1-9.
82.
Nakajima, T., et al., Use and safety of KAATSU training: results of a national
survey. Int J KAATSU Training Res, 2006. 2: p. 5-13.
107
83.
Harmon, J., The significance of local vascular phenomena in production of
ischemic necrosis in skeletal muscle. Am J Pathol, 1948. 24: p. 625-641.
84.
Strock, P. and G. Majno, Microvascular changes in acutely ischemic rat muscle.
Surg Gynecol Obstet, 1969. 129: p. 1213-1224.
85.
Kawada, S., What phenomena do occur in blood flow-restricted muscle? Int J
KAATSU Training Res, 2005. 1: p. 37-44.
86.
Clark, B., et al., Relative safety of 4 weeks of blood flow-restricted resistance
exercise in young, healthy adults. Scand J Med Sci Sports, 2011. 21: p. 653-662.
87.
Madarame, H., et al., Effects of low-intensity resistance exercise with blood flow
restriction on coagulation system in healthy adults. Clin Physiol Funct Imaging,
2010. 30: p. 210-213.
88.
Madarame, H., et al., Haemostatic and inflammatory responses to blood flowrestricted exercise in patients with ischaemic heart disease: a pilot study. Clin
Physiol Funct Imaging, 2013. 33: p. 11-17.
89.
Karabulut, M., et al., Inflammation marker, damage marker and anabolic
hormone responses to resistance training with vascular restriction in older males.
Clin Physiol Funct Imaging, 2013. 33: p. 393-399.
90.
Clarkson, P., K. Nosaka, and B. Braun, Muscle function after exercise-induced
muscle damage and rapid adaptation. Med Sci Sports Exerc, 1992. 24: p. 512520.
91.
Clarkson, P., et al., Serum creatine kinase levels and renal function measures in
exertional muscle damage. Med Sci Sports Exerc, 2006. 38: p. 623-627.
108
92.
Loenneke, J., et al., Blood flow restriction does not result in prolonged
decrements in torque. Eur J Appl Physiol, 2013. 113: p. 923-931.
93.
Loenneke, J. and T. Pujol, Sarcopenia: an emphasis on occlusion training and
dietary protein. HIPPOKRATIA, 2011. 15: p. 132-137.
94.
Rooney, K., R. Herbert, and R. Balnave, Fatigue contributes to the strength
training stimulus. Med Sci Sports Exerc, 1994. 26: p. 1160-1164.
95.
Karabulut, M., et al., The effects of different initial restrictive pressures used to
reduce blood flow and thigh composition on tissue oxygenation of the quadriceps.
J Sports Sci, 2011. 29: p. 951-958.
96.
Kawada, S., What phenomena do occur in blood flow-restricted muscle? Int. J.
Kaatsu Training Res., 2005. 1: p. 37-44.
97.
Signorile, J., et al., Effects of partial occlusion of circulation on frequency and
amplitude of surface electromyography. J Electromyography Kinesiol, 1991. 1: p.
124-129.
98.
Karabulut, M. and G. Perez, Neuromuscular response to varying pressures
created by tightness of restriction cuff. J Electromyography Kinesiol, 2013. 23: p.
1494-1498.
99.
Downs, M., et al., Acute vascular and cardiovascular responses to blood flow
restricted exercise. Med Sci Sports Exerc, 2014. 46: p. 1489-1497.
100.
Loenneke, J., et al., Effects of cuff width on arterial occlusion: implications for
blood flow restricted exercise. Eur J Appl Physiol, 2012. 112: p. 2903-2912.
109
101.
Takano, H., et al., Effects of low-intensity "KAATSU" resistance exercise on
hemodynamic and growth hormone responses. Int. J. Kaatsu Training Res., 2005.
1: p. 13-18.
102.
Hody, S., et al., The susceptibility of the knee extensors to eccentric exerciseinduced muscle damage is not affected by leg dominance but by exercise order.
Clin Physiol Funct Imaging, 2013. 33: p. 373-380.
103.
Cram, J., G. Kasman, and J. Holtz, Introduction to Surface Electromyography.
1998, Gaithersburg, MD: Aspen Publishers, Inc. 408.
104.
Ferrari, M., T. Binzoni, and V. Quaresima, Oxidative metabolism in muscle.
Philos Trans R Soc Lond B Biol Sci, 1997. 352: p. 677-683.
105.
Grassi, B., et al., Muscle oxygenation and pulmonary gas exchange kinetics
during cycling exercise on-transitions in humans. J Appl Physiol, 2003. 95: p.
149-158.
106.
Ferreira, L., et al., Muscle capillary blood flow kinetics estimated from pulmonary
O2 uptake and near-infrared spectroscopy. J Appl Physiol, 2005. 98: p. 18201828.
107.
Miyamoto, N., et al., Non-uniform muscle oxygenation despite uniform
neuromuscular activity within the vastus lateralis during fatiguing heavy
resistance exercise. Clin Physiol Funct Imaging, 2013. 33: p. 463-469.
108.
Yasuda, T., et al., Venous blood gas and metabolite response to low-intensity
muscle contractions with external limb compression. Metabolism, 2010. 59: p.
1510-1519.
110
109.
Wernbom, M., et al., Acute effects of blood flow restriction on muscle activity and
endurance during fatiguing dynamic knee extensions at low load. J Strength Cond
Res, 2009. 23: p. 2389-2395.
110.
Iida, H., et al., Hemodynamic and neurohumoral responses to the restriction of
femoral blood flow by KAATSU in healthy subjects. Eur J Appl Physiol, 2007.
100: p. 275-285.
111.
Barnes, W., The relationship between maximum isometric strength and
intramuscular circulatory occlusion. Ergonomics, 1980. 23: p. 351-357.
112.
Laurentino, G., et al., Effects of strength training and vascular occlusion. Int J
Sports Med, 2008. 29: p. 664-667.
113.
Ferrari, M., L. Mottola, and V. Quaresima, Principles, techniques, and limitations
of near infrared spectroscopy. Can J Appl Physiol, 2004. 29: p. 463-487.
114.
DeLorey, D., J. Kowalchuk, and D. Patterson, Relationship between pulmonary
O2 uptake kinetics and muscle deoxygenation during moderate-intensity exercise.
J Appl Physiol, 2003. 95: p. 113-120.
115.
Berneis, K., et al., Effects of hyper- and hypoosmolality on whole body protein
and glucose kinetics in humans. Am J Physiol Endocrinol Metab, 1999. 276: p.
E188-E195.
116.
Keller, U., et al., Effects of changes in hydration on protein, glucose and lipid
metabolism in man: impact on health. Eur J Clin Nutr, 2003. 57: p. S69-S74.
117.
Akima, H., et al., Vastus lateralis fatigue alters recruitment of musculus
quadriceps femoris in humans. J Appl Physiol, 2002. 92: p. 679-684.
111
118.
Forster, H., et al., Estimation of arterial PO2, PCO2, pH, and lactate from
arterialized venous blood. J Appl Physiol, 1972. 32: p. 134-137.
119.
St Croix, C., et al., Estimation of arterial PCO2 in the elderly. J Appl Physiol,
1995. 79: p. 2086-2093.
120.
Gonzales, J. and B. Scheuermann, Prior heavy exercise increases oxygen cost
during moderate exercise without associated change in surface EMG. J
Electromyography Kinesiol, 2008. 18: p. 99-107.
121.
Dousset, E., et al., Effects of acute hypoxemia on force and surface EMG during
sustained handgrip. Muscle & Nerve, 2001. 24: p. 364-371.
122.
DeBlasi, R., et al., Noninvasive measurement of human forearm oxygen
consumption by near infrared spectroscopy. Eur J Appl Physiol, 1993. 67: p. 2025.
123.
Wagner, P., The critical role of VEGF in skeletal muscle angiogenesis and blood
flow. Biochem Soc Trans, 2011. 39: p. 1556-1559.
124.
Hang, J., et al., VEGF gene expression is upregulated in electrically stimulated
rat skeletal muscle. Am J Physiol Heart Circ Physiol, 1995. 269: p. H1827H1831.
125.
Little, J., et al., Low-volume high-intensity interval training reduces
hyperglycemia and increases muscle mitochondrial capacity in patients with type
2 diabetes. J Appl Physiol, 2011. 111: p. 1554-1560.
126.
Nilsson, B., et al., Group-based aerobic interval training in patients with chronic
heart failure: norwegian ullevaal model. Phys Ther, 2008. 88: p. 523-535.
112
127.
Baechle, T. and R. Earle, Essentials of Strength Training and Conditioning. Third
ed. 2008, Champaign, IL: Human Kinetics. 641.
128.
Murkin, J. and M. Arango, Near-infrared spectroscopy as an index of brain and
tissue oxygenation. Brit J Anaesth, 2009. 103: p. i3-i13.
129.
Burnley, M., et al., Effects of prior heavy exercise on VO2 kinetics during heavy
exercise are related to changes in muscle activity. J Appl Physiol, 2002. 93: p.
167-74.
130.
Barstow, T. and P. Mole, Simulation of pulmonary O2 uptake during exercise
transients in humans. J Appl Physiol, 1987. 63: p. 2253-2261.
131.
Rossiter, H., et al., Inferences from pulmonary O2 uptake with respect to
intramuscular [phosphocreatine] kinetics during moderate exercise in humans. J
Physiol, 1999. 518: p. 921-932.
132.
Keramidas, M., S. Kounalakis, and N. Geladas, The effect of interval training
combined with thigh cuffs pressure on maximal and submaximal exercise
performance. Clin Physiol Funct Imaging, 2012. 32: p. 205-213.
133.
Kumagai, K., et al., Cardiovascular drift during low intensity exercise with leg
blood flow restriction. Acta Physiol Hung, 2012. 99: p. 392-399.
134.
Kacin, A. and K. Strazar, Frequent low-load ischemic resistance exercise to
failure enhances muscle oxygen delivery and endurance capacity. Scand J Med
Sci Sports, 2011. 21: p. e231-e241.
135.
Hickson, R., Interference of strength development by simultaneously training for
strength and endurance. Eur J Appl Physiol, 1980. 45: p. 255-263.
113
136.
Kimball, S., Interaction between the AMP-activated protein kinase and mTOR
signaling pathways. Med Sci Sports Exerc, 2006. 38: p. 1958-1964.
137.
Tabata, I., et al., Effect of high-intensity endurance training on isokinetic muscle
power. Eur J Appl Physiol, 1990. 60: p. 254-258.
114
Appendix A
Activity Level Questionnaire (Chapter 3)
1. Do you currently participate in regular exercise?
□ Yes
□ No
2. How many days a week have you participated in regular exercise?
□ 1-2
□ 3-4
□ 5-7
3. How long have you participated in regular exercise?
□ < 6 weeks
□ 3-6 months
□ 12-24 months
□ 6-8 weeks
□ 6-12 months
□ > 24 months
□ 8-12 weeks
□ >12 months
4. What type of exercise do typically participate in (please check all that apply)?
□ Endurance Training
□ Running
□ Cycling
□ Swimming
□ Rowing
□ Resistance Training
□ Heavy
□ Light
□ Olympic Lifting
□ Eccentric (negative) Lifting
□ Concurrent Training (both)
115
5. Typically, how long (time duration) does each exercise session last?
□ <30 minutes
□ 90-120 minutes
□ 30-60 minutes
□ > 120 minutes
116
□ 60-90 minutes
Appendix B
Activity Questionnaire (Chapters 4-5)
1. Do you currently perform regular exercise (≥2 days/week / ≥1 hour duration) for
the last 6 months (please circle)?
YES
NO
2. If you answered "yes" to question 1, how many days per week on average do you
perform exercise?
3. If you answered "yes" to question 1, what type of exercise do you regularly
perform (please state all forms of exercise)?
4. If you answered "yes" to question 1, how long does a typical exercise session
last?
5. If you answered "yes" to question 1, in the last 12 months what is the longest
duration that you have NOT participated in any regular exercise?
6. If you answered "yes" to question 1, during the past 12 months have you
participated in, or prepared to participate in, a power-lifting and/or bodybuilding
competition (please circle)?
YES
NO
7. If you answered "yes" to question 1, during the past 12 months have you
participated in, or prepared to participate in, a marathon (26.2 miles) competition
(please circle)?
YES
NO
8. Do you, or have you had, a bone or joint problem in the past 12 months?
117
9. Do you, or have you had, a bone or joint problem in the past 12 months that could
be made worse by a change in your physical activity?
10. Do you, or have you had, a concussion or any other neurological disorder in the
past 12 months?
11. Do you lose, or have you ever lost, your balance because of dizziness?
12. Do you lose, or have you ever lost, consciousness?
13. Do you know of any other reason(s) why you should not perform physical
activity?
118
Appendix C
ADULT RESEARCH SUBJECT INFORMATION AND CONSENT FORM
EFFECTS OF VASCULAR OCCLUSION DURING ISOMETRIC KNEE
EXTENSION EXERCISE ON MOTOR UNIT RECRUITMENT PATTERNS
Principal Investigator:
Barry W. Scheuermann, Ph.D.
Other Staff (identified by role):
Trent Cayot, BS (Co-investigator)
Nick Kruse, MS (Graduate Student Research Assistant)
Shinichiro Sugiura, MS (Graduate Student Research Assistant)
Erin Garmyn, BS (Graduate Student Research Assistant)
Aaron Shaw, BS (Graduate Student Research Assistant)
Chris Silette, BS (Graduate Student Research Assistant)
Contact Phone number(s):
(419) 530-2692 0ffice
(419) 530-2058 Lab
What you should know about this research study:

We give you this consent/authorization form so that you may read about the
purpose, risks, and benefits of this research study. All information in this
form will be communicated to you verbally by the research staff as well.

Routine clinical care is based upon the best-known treatment and is
provided with the main goal of helping the individual patient. The main
goal of research studies is to gain knowledge that may help future patients.

We cannot promise that this research will benefit you. Just like routine
care, this research can have side effects that can be serious or minor.
119

You have the right to refuse to take part in this research, or agree to take
part now and change your mind later.

If you decide to take part in this research or not, or if you decide to take part
now but change your mind later, your decision will not affect your routine
care.

Please review this form carefully. Ask any questions before you make a
decision about whether or not you want to take part in this research. If you
decide to take part in this research, you may ask any additional questions at
any time.

Your participation in this research is voluntary.
PURPOSE (WHY THIS RESEARCH IS BEING DONE)
You are being asked to take part in a research study that will measure how your skeletal
muscles respond to varying intensities of a lower-body exercise during normal blood flow
conditions and when the amount of blood flowing to your muscles is reduced (blood flow
restriction condition). Reducing the amount of blood flowing to your muscles may cause
them to fatigue or tire more quickly but does not cause any short- or long-term damage.
You were selected as someone who may want to take part in this study because you
indicated an interest in this study by contacting either Dr. Barry Scheuermann or Trent
Cayot and you meet the criteria outlined below. This study will include 20 participants
recruited from the University of Toledo community.
To participate in this study, you must be between 18-45 years of age and be free of any
known cardiovascular, pulmonary, or metabolic disease as determined by a medical
history questionnaire (Appendix A). If you do not meet these criteria, we appreciate your
willingness to volunteer but unfortunately, you will not be able to participate in this
study.
DESCRIPTION OF THE RESEARCH PROCEDURES AND DURATION OF YOUR
INVOLVEMENT
If you decide to take part in this study, you will be asked to visit the Cardiopulmonary
and Metabolism Research (room HH 1407) laboratory in the Department of Kinesiology
located on the main campus of the University of Toledo in the Health Sciences and
Human Services Building. All testing testing will take place at this location. You will be
asked to visit the Cardiopulmonary and Metabolism Research Laboratory on 5 separate
occasions. The first and final visit will last approximately 2 hours each, with the
remaining 3 visits (Visits 2-4) lasting approximately 1½ hours.
Study Visits
First Visit:
120













You will be asked to arrive to the laboratory having avoided any strenuous
physical activity for 24 hours and having not ingested any caffeine at least 12
hours prior to your visit.
During your first visit, you will be asked to read and sign this informed consent
form, which explains all of the tests and procedures of the research study. You
will be able to ask the investigators any questions regarding the research study
prior to signing the informed consent form.
After you sign the informed consent form, you will be asked to complete a
medical history questionnaire and an activity level questionnaire.
Standard measurements of height, weight, thigh girth (circumference), thigh
skinfold measurements, and resting blood pressure will be recorded.
The maximal strength of your thigh muscles will be evaluated using a leg exercise
(knee extension).
The leg that we will test in the research study is your dominant leg (the leg that
you would use to kick a ball).
You will be asked to sit on the padded exercise seat and perform 2 sets of 4
repetitions of leg exercise using a light- to-moderate amount of weight or
resistance as a warm-up.
During the exercise you will have an ankle strap wrapped around your ankle as
well as a Velcro belt around your hips.
Following the warm-up, you will be asked to contract your leg muscles as hard as
you can and exert a maximal effort for 5 seconds.
You will be asked to repeat this maximal effort a total of 3 times but you will be
provided with a 7 minute rest period between each attempt.
Prior to performing the maximal strength test described above, a small area of
skin over your thigh muscles will be shaved and cleaned before a small adhesive
pad is placed on the skin. A small wire connects the adhesive pad to an electronic
device that is able to record the small electrical signals generated by muscles
(called surface electromyography or EMG) when they are asked to forcefully
contract. A small block will also be placed on the skin and secured in place with
Velcro straps. This device (called near infrared spectroscopy or NIRS) is able to
record the how oxygen is transported within the muscle during exercise. A blood
flow restriction cuff will also be wrapped around you upper thigh. The cuffs are
similar to the blood pressure cuffs used for your arms just larger in size. The cuff
will be inflated with air in order to apply pressure to the thigh muscles during a
portion of the test.
After completion of the maximal effort leg exercise, you will be given a 10
minute recovery period.
Following the 10 minute recovery period you will be asked to perform 4
repetitions of the leg exercise at low or moderate intensities. Each contraction
will last 5 seconds and you will have a 30 second rest period between each
contraction. After each set of contractions you will recieve a 10 minute recovery
period.
121


During each set the exercise intensity will remain the same but the blood flow
restriction condition will change. During one set of exercise there will be no
blood flow restriction. During another set of exercise there will be blood flow
restriction only during the time you perform the exercise. During the last set of
exercise there will be blood flow restriction for 5 minutes before exercise and
continued during exercise. In order to restrict (slow) blood flow the cuff that was
placed around you thigh will be inflated with air. The cuff will be deflated (air
released) immediately after the exercise set is complete. The cuff will also be
deflated anytime, for any reason, at your choosing.
After the last exercise set you will be given a 10 minute recovery period.
Following the 10 minute recovery period the cuff will be filled with air at a higher
(but safe) pressure and you will be asked to remain seated for 5 minutes.
Visits Two to Five:


During visits 2 to 5, you will be asked to participate in a sequence of exercises
that will be very similar to the first visit.
The only variable that is different between visit 1 and visits 2 - 5 is that the
exercise intensity will change during each visit.
Preparation Steps:




A small area of skin will be shaved and cleaned before a small plastic sensor is
placed on the surface of the skin over the muscles of your thigh.
The sensor will be secured on your thigh using a velcro strap and adhesive tape.
The sensor on your skin measures the amount of oxygen that is being delivered to
your muscles using a technique called Near Infrared Spectroscopy (NIRS). NIRS
is a safe, non-invasive method that used different types of light to measure how
much oxygen is bound to the hemoglobin in the small blood vessels of your legs.
An adhesive pad will be placed on the surface of the skin overlying the muscles of
your thigh to record the small electrical signals generated by muscles (surface
EMG).
Maximal Occlusion Test:


In order to compare your results with other participants in this study, we need you
to complete a standardization test where we increase the pressure in the cuff
around your thigh to 240 mm Hg for 5 minutes and measure the change in oxygen
delivery to your muscle during this time.
This test will be performed after to the exercise protocol during each visit 1 to 5.
Blood Flow Restriction Conditions:

There will be 3 blood flow restriction conditions that will be tested during this
research study.
122
o Control - the cuff will not be inflated during exercise and therefore
there will be no blood flow restriction occuring due to the cuff.
o Immediate Blood Flow Restriction - the cuff will be inflated
immediately before the exercise set begins and blood flow will be
restricted (slowed) during exercise. The cuff will be immediately
deflated after the exercise set is complete.
o Pre-Blood Flow Restriction - the cuff will be inflated 5 minutes before
the exercise set begins and blood flow will be restricted (slowed) both
before and during exercise. The cuff will be immediately deflated
after the exercise set is complete.
Exercise Intensities:


The exercise intensities that will be tested during this research study will be
calculated by using your peak force that you produced while performing the
maximal effort leg exercise during visit 1.
The exercise intensities include:
o 20% of the peak force
o 40% of the peak force
o 60% of the peak force
o 80% of the peak force
o 100% of the peak force
RISKS AND DISCOMFORTS YOU MAY EXPERIENCE IF YOU TAKE PART IN
THIS RESEARCH
Immediate risks may include muscle cramping, strain, or soreness during the exercise,
especially following the maximal exercise test.
You may also experience numbness, tingling sensation, or brusing in the lower
extremities during the duration of the blood flow restriction conditions (while the blood
pressure cuffs are inflated). Numbness and tingling sensations will stop immediately
upon the release of the pressure in the blood pressure cuffs. There is a small potential
risk that a venous clot may develop during the blood flow restriction period but this risk
will be minimized by indicating on the medical history questionnaire if you have any
hereditary conditions that may cause your blood to clot easily. There exists a low, but
unknown, risk of developing chronic venous insufficiency (difficulties with blood flow
out of the leg) and/or deep vein thrombosis (blood clot within the leg) in the lower
extremities in the future following blood flow restriction exercise. This risk will be
minimized by indicating on the medical history questionnaire if you have any hereditary
conditions that may cause your blood to clot easily.
123
Table 1. Side Effects of KAATSU Training and Their Occurrence in Each Type of
Facility.
Side Effect
Total Hospita Osteopa Acupun Rehab Gyms
Other
l&
th’s
cturist’s Center
Clinics
Office
Office
Subcutaneous
1651
156
300
86
2
1105
2
Hemorrhage
(“Brusing”)
Numbness
164
6
67
42
1
48
Cerebral
35
10
3
21
1
Anemia
Cold
16
2
10
1
3
Feeling
Venous
7
1
3
3
Thrombus
Pain
5
1
4
Itch
3
3
Deterioration of
2
2
Ischemic Heart
Feeling Sick
2
1
1
Icrease Blood
2
1
1
Pressure
Physical
2
1
1
Weariness
Dizziness
2
2
Pulmonary
1
1
Embolism
Rhabdomyolysis
1
1
Palpitation
1
1
Nosebleed
1
1
Deterioration of
1
1
Diabetic
Retinopathy
Fainting
1
1
Cerebral
1
1
Infarction
Hypoglycemia
1
1
Edema
1
1
Chafe
1
1
There were a total of 31,754 visits to facilities for vascular occlusion (KAATSU) training
annually according to the referenced article below. This included 5,311 visits from
124
athletes, 2,776 visits from orthopedic patients, 5,382 visits from an elderly population,
and 15,284 visits from healthy adults.
Nakajima t, Kurano M, Iida H, Takano H, Oonuma, H, Morita T, Meguro K, Sato Y,
Nagata T, and KAATSU Training Group (2006) Use and safety of KAATSU training:
Results of a national survey. Int J KAATSU Training Res 2: 5-13.
There are no known risks and/or discomfort associated with measuring oxygen delivery
using near-infrared spectroscopy (NIRS) techniques or with measuring electrical activity
of the muscles using electromyography (EMG).
POSSIBLE BENEFIT TO YOU IF YOU DECIDE TO TAKE PART IN THIS
RESEARCH
There is no direct benefit from participating in this study to the participants. Students
from the Department of Kinesiology that participate in this study will be exposed to
current research topics and techniques.
COST TO YOU FOR TAKING PART IN THIS STUDY
There are no costs associated with participating in this study.
PAYMENT OR OTHER COMPENSATION TO YOU FOR TAKING PART IN THIS
RESEARCH
If you decide to take part in this research you will not receive any payment or
compensation for participating in this research nor will you be given “extra credit” in any
academic courses that you are enrolled.
ALTERNATIVE(S) TO TAKING PART IN THIS RESEARCH
No alternative procedures or treatments will be made available since this research does
not incorporate any procedures or treatments that affect the subject.
CONFIDENTIALITY - (USE AND DISCLOSURE OF YOUR PROTECTED HEALTH
INFORMATION)
The researchers will make every effort to prevent anyone who is not on the research team
from knowing that you provided this information, or what that information is. The
consent forms with signatures will be kept separate from responses, which will not
include names and which will be presented to others only when combined with other
responses. Although we will make every effort to protect your confidentiality, there is a
low risk that this might be breached.
IN THE EVENT OF A RESEARCH-RELATED INJURY
In the event of injury resulting from your taking part in this study, treatment can be
obtained at a health care facility of your choice. You should understand that the costs of
such treatment will be your responsibility. Financial compensation is not available
through The University of Toledo or The University of Toledo Medical Center. By
signing this form you are not giving up any of your legal rights as a research participant.
125
In the event of a study-related injury, you may contact Dr. Barry Scheuermann any time
of the day or night at 567-288-9732.
VOLUNTARY PARTICIPATION
Taking part in this study is voluntary. You may refuse to participate or discontinue
participation at any time without penalty or a loss of benefits to which you are otherwise
entitled. If you decide not to participate or to discontinue participation, your decision
will not affect your future relations with the University of Toledo or The University of
Toledo Medical Center.
NEW FINDINGS
You will be notified of new information that might change your decision to be in this
study if any becomes available.
OFFER TO ANSWER QUESTIONS
Before you sign this form, please ask any questions on any aspect of this study that is
unclear to you. You may take as much time as necessary to think it over. If you have
questions regarding the research at any time before, during or after the study, you may
contact Dr. Barry Scheuermann (419-530-2692) or Trent Cayot
([email protected]).
If you have questions beyond those answered by the research team or your rights as a
research subject or research-related injuries, please feel free to contact the Chairperson of
the University of Toledo Biomedical Institutional Review Board at 419-383-6796.
SIGNATURE SECTION (Please read carefully)
YOU ARE MAKING A DECISION WHETHER OR NOT TO PARTICIPATE IN THIS
RESEARCH STUDY. YOUR SIGNATURE INDICATES THAT YOU HAVE READ
THE INFORMATION PROVIDED ABOVE, YOU HAVE HAD ALL YOUR
QUESTIONS ANSWERED, AND YOU HAVE DECIDED TO TAKE PART IN THIS
RESEARCH.
BY SIGNING THIS DOCUMENT YOU AUTHORIZE US TO USE OR
DISCLOSE YOUR PROTECTED HEALTH INFORMATION AS DESCRIBED IN
THIS FORM.
The date you sign this document to enroll in this study, that is, today’s date, MUST fall
between the dates indicated on the approval stamp affixed to the bottom of each page.
These dates indicate that this form is valid when you enroll in the study but do not reflect
how long you may participate in the study. Each page of this Consent/Authorization
Form is stamped to indicate the form’s validity as approved by the UT Biomedical
Institutional Review Board (IRB).
126
Appendix D
ADULT RESEARCH SUBJECT INFORMATION AND CONSENT FORM
THE ACUTE EFFECTS OF VASCULAR OCCLUSION DURING SUBMAXIMAL ENDURANCE EXERCISE
Principal Investigator:
Barry W. Scheuermann, Ph.D.
Other Staff (identified by role): Trent Cayot, BS (Co-investigator)
David L. Weldy, MD, Ph.D. (Co-investigator)
Michael Tevald, PT, Ph.D. (Co-investigator)
Nick Kruse, MS (Graduate Assistant)
Shinichiro Sugiura, MS (Graduate Assistant)
Contact Phone number(s):
(419) 530-2692 0ffice
(419) 530-2058 Lab
What you should know about this research study:

We give you this consent/authorization form so that you may read about the
purpose, risks, and benefits of this research study. All information in this
form will be communicated to you verbally by the research staff as well.

Routine clinical care is based upon the best-known treatment and is
provided with the main goal of helping the individual patient. The main
goal of research studies is to gain knowledge that may help future patients.

We cannot promise that this research will benefit you. Just like routine
care, this research can have side effects that can be serious or minor.
127

You have the right to refuse to take part in this research, or agree to take
part now and change your mind later.

If you decide to take part in this research or not, or if you decide to take part
now but change your mind later, your decision will not affect your routine
care.

Please review this form carefully. Ask any questions before you make a
decision about whether or not you want to take part in this research. If you
decide to take part in this research, you may ask any additional questions at
any time.

Your participation in this research is voluntary.
PURPOSE (WHY THIS RESEARCH IS BEING DONE)
You are being asked to take part in a research study that will measure how your blood
vessels and skeletal muscles respond to moderate effort cycling exercise during normal
blood flow conditions and when the amount of blood flowing to your muscles is reduced
(blood flow restriction condition). Reducing the amount of blood flowing to your
muscles may cause them to fatigue or tire more quickly but does not cause any short- or
long-term damage.
You were selected as someone who may want to take part in this study because you
indicated an interest in this study by contacting either Dr. Barry Scheuermann or Trent
Cayot and you meet the criteria outlined below. This study will include 12 participants
recruited from the University of Toledo community.
To participate in this study, you must be a male between 18-45 years of age and be free
of any known cardiovascular, pulmonary, or metabolic disease as determined by a
medical history questionnaire. If you do not meet these criteria, we appreciate your
willingness to volunteer but unfortunately, you will not be able to participate in this
study.
DESCRIPTION OF THE RESEARCH PROCEDURES AND DURATION OF YOUR
INVOLVEMENT
If you decide to take part in this study, you will be asked to visit the Cardiopulmonary
and Metabolism Research (room HH 1407) and the Neuromuscular Physiology (room
HH 1700) laboratories in the Department of Kinesiology located on the main campus of
the University of Toledo in the Health Sciences and Human Services Building. All
testing testing will take place at this location. You will be asked to visit the
Cardiopulmonary and Metabolism Research Laboratory on 4 separate occasions. The first
visit will last approximately 2-3 hours, with the remaining 3 visits lasting approximately
2-2½ hours.
Study Visits
First Visit:
128












You will be asked to arrive to the laboratory having avoided any strenuous
physical activity for 24 hours prior to your visit.
During your first visit, you will be asked to read and sign this informed consent
form, which explains all of the tests and procedures of the research study. You
will be able to ask the investigators any questions regarding the research study
prior to signing the informed consent form.
After you sign the informed consent form, you will be asked to complete a
medical history questionnaire.
Standard measurements of height, weight, body fat composition, thigh girth, thigh
skinfold measurements, resting heart rate, and resting blood pressure will be
recorded.
The maximal strength of your thigh muscles will be evaluated using a leg exercise
machine.
You will be asked to sit on the exercise machine and perform 2 sets of 10
repetitions of leg exercise using a light- to-moderate amount of weight or
resistance as a warm-up.
Following the warm-up, you will be asked to contract your leg muscles as hard as
you can and exert a maximal effort for 5 seconds.
You will be asked to repeat this maximal effort a total of 3 times but you will be
provided with a 3 minute rest period between each attempt.
Prior to performing the maximal strength test described above, a small area of
skin over your thigh muscles will be shaved and cleaned before a small adhesive
pad is placed on the skin. A small wire connects the adhesive pad to an electronic
device that is able to record the small electrical signals generated by muscles
(called surface electromyography or EMG) when they are asked to forcefully
contract.
After the maximal strength of muscles has been determined, you will rest for 20
to 30 minutes sitting comfortably in a chair until the next test begins.
Following the rest period, you will be asked to perform a maximal exercise test on
a stationary exercise bike. The exercise intensity will be very easy at the
beginning of the test and will become progressively more difficult until you
finally reach a point where you can no longer turn the pedals at a rate equal to 40
revolutions each minute. During this test you will also be asked to wear a
noseclip and breathe through a plastic mouthpiece so that we can analyze a
sample of the air that you breathe out. This tells us how much oxygen you are
using for energy and is a measure of your overall level of fitness.
Electromyography (EMG) will also be used to measure the electrical activity of
your thigh muscles during this maximal exercise test, similar to the previous test
of your maximal strength.
Visits Two to Four:

During visits 2 to 4, you will be asked to participate in a sequence of procedures
and tests that will be very similar during each of the visits.
129
Preparation Steps:









A small area of skin will be shaved and cleaned before a small plastic sensor is
placed on the surface of the skin over the muscles of your thigh.
The sensor will be secured on your thigh using a velcro strap and adhesive tape.
The sensor on your skin measures the amount of oxygen that is being delivered to
your muscles using a technique called Near Infrared Spectroscopy (NIRS). NIRS
is a safe, non-invasive method that used different types of light to measure how
much oxygen is bound to the hemoglobin in the small blood vessels of your legs.
Similar to the first visit, an adhesive pad will be placed on the surface of the skin
overlying the muscles of your thigh to record the small electrical signals
generated by muscles (surface EMG).
You will be asked to wear a heart rate monitor that is placed around your chest
and a blood pressure cuff that is place around your upper left arm in order to
monitor heart rate and blood pressure throughout each session.
You will be asked to lie down on your back on a padded table while a small,
flexible, sterilized needle (catheter) can be placed in a blood vessel (vein) in the
back of your hand for blood sampling. The needle will be removed leaving a
small flexible tube in your vein which will be secured in place by using tape. The
tube will remain in place throughout the duration of the exercise and recovery
period.
During each of the visits 2 to 4, your hand and forearm will be wrapped in a
heating pad which will help in obtaining the blood samples during exercise and
recovery.
Blood flow to your legs will be controlled by placing cuffs around each thigh.
The cuffs are similar to the cuffs used to measure blood pressure in your arms,
just larger.
The cuffs will be connected to an inflator which will immediately inflate or
deflate the thigh cuffs to the specific blood flow restriction condition being
studied that day (described below).
Maximal Occlusion Test:


In order to compare your results with other participants in this study, we need you
to complete a standardization test where we increase the pressure in the cuff
around your thigh to 240 mm Hg for 5 minutes and measure the change in oxygen
delivery to your muscle during this time.
This test will be performed prior to the exercise protocol during each visit 2 to 4.
Exercise Protocol Test:
130



After no less than 10 minutes of recovery from the occlusion period, the cuffs will
be inflated to one of the three conditions (wich are explained below) for 5 minutes
while you sit on the exercise bike. At the end of this period, you will be asked to
begin your warm-up exercise for 5 additional minutes prior to beginning 20
minutes of moderate intensity exercise.
At the end of exercise, you will be moved back to the chair where you will rest
comfortably for the next 60 minutes.
During each of these visits, one of the following conditions will be applied during
cycling;
- Control (CON) – no blood flow restriction or normal blood flow to your legs
- Low (LOW) – small decrease in blood flow to the muscles of your legs
- Moderate (MOD) – moderate decrease in blood flow to the muscles of your legs


Blood samples will be obtained at rest prior to exercise and at 10 minute intervals
during exercise and recovery. The total volume of blood drawn during each of
the visits 3-5 will be approximately 2 tablespoons or 30 milliliters.
It is expected that it will require approximately 2-2½ hours to complete all testing
during each of the visits 2 to 4.
RISKS AND DISCOMFORTS YOU MAY EXPERIENCE IF YOU TAKE PART IN
THIS RESEARCH
Immediate risks may include muscle cramping, strain, or soreness during the cycling
exercise, especially following the maximal exercise test. You may also experience
numbness, tingling sensation, or bruising in the lower extremities during the duration of
the blood flow restriction conditions (while the blood pressure cuffs are inflated).
Numbness and tingling sensations will stop immediately upon the release of the pressure
in the blood pressure cuffs. There is a small potential risk that a venous clot may develop
during the blood flow restriction period but this risk will be minimized by indicating on
the medical history questionnaire if you have any hereditary conditions that may cause
your blood to clot easily. There exists a low, but unknown, risk of developing chronic
venous insufficiency (difficulties with blood flow out of the leg) and/or deep vein
thrombosis (blood clot within the leg) in the lower extremities in the future following
blood flow restriction exercise. This risk will be minimized by indicating on the medical
history questionnaire if you have any hereditary conditions that may cause your blood to
clot easily.
131
Table 1. Side Effects of KAATSU Training and Their Occurrence in Each Type of
Facility.
Side Effect
Total Hospita Osteopa Acupun Rehab Gyms
Other
l&
th’s
cturist’s Center
Clinics
Office
Office
Subcutaneous
1651
156
300
86
2
1105
2
Hemorrhage
(“Brusing”)
Numbness
164
6
67
42
1
48
Cerebral
35
10
3
21
1
Anemia
Cold
16
2
10
1
3
Feeling
Venous
7
1
3
3
Thrombus
Pain
5
1
4
Itch
3
3
Deterioration of
2
2
Ischemic Heart
Feeling Sick
2
1
1
Icrease Blood
2
1
1
Pressure
Physical
2
1
1
Weariness
Dizziness
2
2
Pulmonary
1
1
Embolism
Rhabdomyolysis
1
1
Palpitation
1
1
Nosebleed
1
1
Deterioration of
1
1
Diabetic
Retinopathy
Fainting
1
1
Cerebral
1
1
Infarction
Hypoglycemia
1
1
Edema
1
1
Chafe
1
1
There were a total of 31,754 visits to facilities for vascular occlusion (KAATSU) training
annually according to the referenced article below. This included 5,311 visits from
132
athletes, 2,776 visits from orthopedic patients, 5,382 visits from an elderly population,
and 15,284 visits from healthy adults.
Nakajima t, Kurano M, Iida H, Takano H, Oonuma, H, Morita T, Meguro K, Sato Y,
Nagata T, and KAATSU Training Group (2006) Use and safety of KAATSU training:
Results of a national survey. Int J KAATSU Training Res 2: 5-13.
Some discomfort may occur during the collection of blood samples and slight bruising
around the insertion site of the needle may appear however, any bruising or soreness
should fade within one to two days.
There are no known risks and/or discomfort associated with measuring oxygen delivery
using near-infrared spectroscopy (NIRS) techniques or with measuring pulmonary gas
exchange (oxygen utilization).
POSSIBLE BENEFIT TO YOU IF YOU DECIDE TO TAKE PART IN THIS
RESEARCH
There is no direct benefit from participating in this study to the participants. Students
from the Department of Kinesiology that participate in this study will be exposed to
current research topics and techniques.
COST TO YOU FOR TAKING PART IN THIS STUDY
There are no costs associated with participating in this study.
PAYMENT OR OTHER COMPENSATION TO YOU FOR TAKING PART IN THIS
RESEARCH
If you decide to take part in this research you will not receive any payment or
compensation for participating in this research nor will you be given “extra credit” in any
academic courses that you are enrolled.
ALTERNATIVE(S) TO TAKING PART IN THIS RESEARCH
No alternative procedures or treatments will be made available since this research does
not incorporate any procedures or treatments that affect the subject.
CONFIDENTIALITY - (USE AND DISCLOSURE OF YOUR PROTECTED HEALTH
INFORMATION)
The researchers will make every effort to prevent anyone who is not on the research team
from knowing that you provided this information, or what that information is. The
consent forms with signatures will be kept separate from responses, which will not
include names and which will be presented to others only when combined with other
responses. Although we will make every effort to protect your confidentiality, there is a
low risk that this might be breached.
IN THE EVENT OF A RESEARCH-RELATED INJURY
In the event of injury resulting from your taking part in this study, treatment can be
obtained at a health care facility of your choice. You should understand that the costs of
133
such treatment will be your responsibility. Financial compensation is not available
through The University of Toledo or The University of Toledo Medical Center. By
signing this form you are not giving up any of your legal rights as a research participant.
In the event of a study-related injury, you may contact Dr. Barry Scheuermann any time
of the day or night at 567-288-9732.
VOLUNTARY PARTICIPATION
Taking part in this study is voluntary. You may refuse to participate or discontinue
participation at any time without penalty or a loss of benefits to which you are otherwise
entitled. If you decide not to participate or to discontinue participation, your decision
will not affect your future relations with the University of Toledo or The University of
Toledo Medical Center.
NEW FINDINGS
You will be notified of new information that might change your decision to be in this
study if any becomes available.
OFFER TO ANSWER QUESTIONS
Before you sign this form, please ask any questions on any aspect of this study that is
unclear to you. You may take as much time as necessary to think it over. If you have
questions regarding the research at any time before, during or after the study, you may
contact Dr. Barry Scheuermann (419-530-2692) or Trent Cayot
([email protected]).
If you have questions beyond those answered by the research team or your rights as a
research subject or research-related injuries, please feel free to contact the Chairperson of
the University of Toledo Biomedical Institutional Review Board at 419-383-6796.
SIGNATURE SECTION (Please read carefully)
YOU ARE MAKING A DECISION WHETHER OR NOT TO PARTICIPATE IN THIS
RESEARCH STUDY. YOUR SIGNATURE INDICATES THAT YOU HAVE READ
THE INFORMATION PROVIDED ABOVE, YOU HAVE HAD ALL YOUR
QUESTIONS ANSWERED, AND YOU HAVE DECIDED TO TAKE PART IN THIS
RESEARCH.
BY SIGNING THIS DOCUMENT YOU AUTHORIZE US TO USE OR
DISCLOSE YOUR PROTECTED HEALTH INFORMATION AS DESCRIBED IN
THIS FORM.
The date you sign this document to enroll in this study, that is, today’s date, MUST fall
between the dates indicated on the approval stamp affixed to the bottom of each page.
These dates indicate that this form is valid when you enroll in the study but do not reflect
how long you may participate in the study. Each page of this Consent/Authorization
Form is stamped to indicate the form’s validity as approved by the UT Biomedical
Institutional Review Board (IRB).
134
Appendix E
ADULT RESEARCH SUBJECT INFORMATION AND CONSENT FORM
THE EFFECTS OF BLOOD FLOW RESTRICTION DURING INTERVAL
CYCLING EXERCISE
Principal Investigator:
Barry W. Scheuermann, Ph.D.
Other Staff (identified by role): David Weldy, MD, PhD
Trent E. Cayot, BS, CSCS
Jakob D. Lauver, MS, CSCS
Contact Phone number(s):
(419) 530-2692 Office
(419) 530-2058 Lab
What you should know about this research study:





We give you this consent/authorization form so that you may read about the
purpose, risks, and benefits of this research study. All information in this
form will be communicated to you verbally by the research staff as well.
Routine clinical care is based upon the best-known treatment and is
provided with the main goal of helping the individual patient. The main
goal of research studies is to gain knowledge that may help future patients.
We cannot promise that this research will benefit you. Just like routine
care, this research can have side effects that can be serious or minor.
You have the right to refuse to take part in this research, or agree to take
part now and change your mind later.
If you decide to take part in this research or not, or if you decide to take part
now but change your mind later, your decision will not affect your routine
care.
135


Please review this form carefully. Ask any questions before you make a
decision about whether or not you want to take part in this research. If you
decide to take part in this research, you may ask any additional questions at
any time.
Your participation in this research is voluntary.
PURPOSE (WHY THIS RESEARCH IS BEING DONE)
You are being asked to take part in a research study that will observed the training
responses to a short-term (2 week) interval training program performed on a stationary
bike. The purpose of the study is to compare three short-term interval training programs
and observe the effects that each training program has on your aerobic capacity (your
ability to perform long-term endurance activity), your anaerobic capacity (your ability to
perform high intensity, short-term activity), and your muscular strength.
You were selected as someone who may want to take part in this study because you
indicated an interest in this study by either contacting Dr. Barry Scheuermann, Dr. David
Weldy, Trent Cayot and/or Jakob Lauver and you meet the criteria outlined below. This
study will include 45 subjects recruited from the University of Toledo Community.
In order to participate in this study, you must be between the ages of 18-40 years and be
free of any known cardiovascular, pulmonary, and/or metabolic diseases as determined
by a medical history questionnaire and an activity level questionnaire. If you do not meet
these criteria, we greatly appreciate your willingness to volunteer but unfortunately, you
will not be able to participate in this study.
DESCRIPTION OF THE RESEARCH PROCEDURES AND DURATION OF YOUR
INVOLVEMENT
If you decide to take part in this study, you will be asked to report to the
Cardiopulmonary and Metabolism Research Laboratory (room 1407, Health Science
Human Service Building, University of Toledo) on 10 separate occasions within a four
week period. Each session will last approximately 1-2 hours in duration. You will
complete 4 assessment sessions (2 pre-training assessment sessions and 2 post-training
assessment sessions) and 6 training sessions. All exercise performed during the study
will be performed on a stationary bike. You will be asked to not participate in any
exercise and/or strenuous activity 24 hours prior to each session.
Day 1: Pre-Training Assessment Session
During the first pre-training assessment session, the research procedures will be
explained to you by the research investigator(s) and you will be given an informed
consent form. You will be encouraged to ask any questions regarding the research study
to the research investigator(s). Also please remember that you can take as much time as
you need to make an informed decision regarding your participation in the study. You
are solely volunteering to participate in the research study and you can stop your
participation within the research study at anytime, for any reason, without any
consequence. Once you feel comfortable with the research procedures, if you would still
like to participate within the research study, you will have to provide written informed
136
consent (by signing this document). Next you will be asked to complete a medical
history questionnaire and an activity level questionnaire that will help to determine if you
meet the criteria defined above for participation within the research study.
Standard physiological baseline measurements will be recorded including: age (years),
height (meters, m), weight (kilogram, kg), thigh circumference (centimeters, cm), thigh
skinfold (millimeters, mm), resting heart rate (beats per minute, bpm), resting blood
pressure (millimeters of mercury, mmHg), and total body fat composition (percent body
fat, %fat).
You will then be asked to perform on ramp test on a stationary bike where you will
warm-up for 4 minutes at a low intensity and then the resistance that you pedal against
will increase by 20 watts per minute (W/min) until you fatigue. You will be asked to
perform the ramp test at a cycling cadence of ≥80 revolutions per minute (rpm). While
you are performing the ramp test you will breathe through a mouthpiece with your noise
occluded by a noise clip. By having you breathe through a mouthpiece we will be able to
record oxygen uptake, carbon dioxide output and ventilation during exercise. We will
also secure an electrode on the surface of the skin of your front thigh muscle using a
Velcro strap. This electrode (near-infrared spectroscopy, NIRS) will measure how your
blood flow within your leg muscle changes during exercise.
Day 2: Pre-training Assessment Session
During the second pre-training assessment you will be asked to perform a maximal
strength test (one-repetition maximum, 1RM) for your front thigh muscle. You will
complete two warm-up sets (10 repetitions and 6 repetitions) of the leg exercise (knee
extension) at low intensities/resistive loads. Following the warm-up sets, you will
attempt to complete a 1RM of the leg exercise (knee extension) by lifting the maximum
amount of weight for one repetition. You will have up to 5 attempts to complete your
1RM and if multiple attempts are needed you will receive a 3-5 minute recovery period
between each 1RM attempt.
Following the successful completion of the 1RM assessment you will be given a 15
minute recovery period prior to completing a critical power test on a stationary bike. You
will warm-up for 4 minutes at a low intensity and then a heavy resistance will be applied
to the bike and you will be asked to cycle as fast as you can for three minutes. During the
critical power test you will be asked to breathe through a mouth piece with your noise
occluded by a nose clip and the NIRS electrode will be secured, via a Velcro strap, to the
front of your thigh.
Days 3-8: Interval Training Sessions
You will complete 6 training sessions in which you will perform cardiovascular interval
training on a stationary bike within a 2 week duration. Each training session will be
separated by 24-72 hours and you will be asked to not participate in any exercise and/or
strenuous activity 24 hours prior to each training session. For the purpose of the research
study an "interval" will be defined as one 60 second high-intensity bout of cycling
exercise followed by one 60 second low-intensity bout of exercise. You will complete 8
137
intervals during the first and second training session, 10 intervals during the third and
fourth training sessions, and 12 intervals during the fifth and sixth training sessions.
At the beginning of your participation you will be randomly assigned to one training
group (high-intensity interval training, HIIT; low-intensity interval training, LIIT; blood
flow restricted low-intensity interval training, BFR-LIIT). The low-intensity resistance
will remain constant across all training groups and will be set at 40 watts. The highintensity resistance for the HIIT group will be higher than the high-intensity resistance
for the LIIT and BFR-LIIT groups. The BFR-LIIT group will have elastic cuffs placed
around both upper thighs and the cuffs will be inflated to a moderate pressure during
exercise. The cuffs will be automatically inflated immediately at the beginning of the
first interval and subsequently be immediately deflated at the end of the last highintensity bout of exercise. Each session you will perform a 4 minute warm-up and cooldown at a low cycling intensity before and after the interval exercise.
During training session 1 and training session 6 you will be asked to breathe through a
mouthpiece with your noise occluded by a noise clip. The NIRS electrode and two other
electrodes (surface electromyography, sEMG) will be secured to the surface of the skin of
the front thigh muscles by a Velcro strap and tape, respectively. The sEMG electrodes
will allow the electrical activity of the muscle to be recorded during exercise. 13-17
blood samples (~0.2 tablespoons, 3 milliliters each) will be taken during the first and
sixth training session, resulting in a total blood sample volume of (~2.6-3.4 tablespoons,
39-51 milliliters). A qualified, experienced professional will place a catheter in the back
of your right hand and collect all of the blood samples.
Day 9 and Day 10: Post-training Assessment Sessions
During the post-training assessment sessions you will complete the same assessments
under the same conditions in the same order as you did during the pre-training assessment
sessions.
RISKS AND DISCOMFORTS YOU MAY EXPERIENCE IF YOU TAKE PART IN
THIS RESEARCH
Immediate risks may include muscle cramping, strain, or soreness during the cycling
exercise, especially following the maximal fatigue exercise assessments.
You may also experience numbness, tingling sensation, or bruising in the lower
extremities (legs) during the duration of the blood flow restriction conditions (while the
elastic cuffs are inflated). Numbness and tingling sensations will stop immediately upon
the deflation of the elastic cuffs. There is a small potential risk that a venous clot may
develop during the blood flow restriction period but this risk will be minimized by
indicating on the medical history and activity level questionnaires if you have any
hereditary conditions that may cause your blood to clot easily. There exists a low, but
unknown, risk of developing chronic venous insufficiency (difficulties with blood flow
out of the leg) and/or deep vein thrombosis (blood clot within the leg) in the lower
extremities (leg) in the future following blood flow restriction exercise. The risk will be
138
minimized by indicating on the medical history and activity level questionnaires if you
have any hereditary conditions that may cause your blood to clot easily.
Table 1. Side Effects of KAATSU Training and Their Occurrence in Each Type of
Facility.
Side Effect
Total Hospita Osteopa Acupun Rehab Gyms
Other
l&
th’s
cturist’s Center
Clinics
Office
Office
Subcutaneous
1651
156
300
86
2
1105
2
Hemorrhage
(“Brusing”)
Numbness
164
6
67
42
1
48
Cerebral
35
10
3
21
1
Anemia
Cold
16
2
10
1
3
Feeling
Venous
7
1
3
3
Thrombus
Pain
5
1
4
Itch
3
3
Deterioration of
2
2
Ischemic Heart
Feeling Sick
2
1
1
Icrease Blood
2
1
1
Pressure
Physical
2
1
1
Weariness
Dizziness
2
2
Pulmonary
1
1
Embolism
Rhabdomyolysis
1
1
Palpitation
1
1
Nosebleed
1
1
Deterioration of
1
1
Diabetic
Retinopathy
Fainting
1
1
Cerebral
1
1
Infarction
Hypoglycemia
1
1
Edema
1
1
Chafe
1
1
139
There were a total of 31,754 visits to facilities for vascular occlusion (KAATSU) training
annually according to the referenced article below. This included 5,311 visits from
athletes, 2,776 visits from orthopedic patients, 5,382 visits from an elderly population,
and 15,284 visits from healthy adults.
Nakajima t, Kurano M, Iida H, Takano H, Oonuma, H, Morita T, Meguro K, Sato Y,
Nagata T, and KAATSU Training Group (2006) Use and safety of KAATSU training:
Results of a national survey. Int J KAATSU Training Res 2: 5-13.
Some discomfort may occur during the collection of blood samples and slight bruising
around the insertion site of the needle may appear, however, any bruising or soreness
should fade within 1-2 days. The few potential risks associated with the surface
electromyography (sEMG) electrodes include allergic reaction of skin to adhesives and
mild soreness and rash from skin preperation prior to using the sEMG electrodes. There
are no known risks and/or discomforts associated with measuring blood flow and oxygen
delivery using near-infrared spectroscopy (NIRS) and/or pulmonary gas exchange
techniques.
POSSIBLE BENEFIT TO YOU IF YOU DECIDE TO TAKE PART IN THIS
RESEARCH
We cannot and do not guarantee or promise that you will receive any benefits from this
research study. The benefit of participating in this study is to help further research
regarding the effects of different types of exercise programs.
COST TO YOU FOR TAKING PART IN THIS STUDY
You are not directly responsible for making any type of payment to take part in this
research study. However, you are responsible for providing your own means of
transportation to and from the Cardiopulmonary and Metabolism Research Laboratory at
The University of Toledo's main campus in the Health Science and Human Services
Building (room 1407). You will not be compensated for gas, travel, or any other
expenses to participate in this research study.
PAYMENT OR OTHER COMPENSATION TO YOU FOR TAKING PART IN THIS
RESEARCH
No compensation including money, free treatment, free medications, or free
transportation will be provided for this study.
PAYMENT OR OTHER COMPENSATION TO THE RESEARCH SITE
The University of Toledo is not receiving money or other benefits from the sponsor of
this research as reimbursement for conducting the research.
ALTERNATIVE(S) TO TAKING PART IN THIS RESEARCH
There are no alternatives to participating in this research study. Exclusion from the
study, however, will not affect the quality of care you may receive at the sports
medicine/physical therapy facility, doctor's office, and/or other medical facilities.
140
CONFIDENTIALITY - (USE AND DISCLOSURE OF YOUR PROTECTED HEALTH
INFORMATION)
The researchers will make every effort to prevent anyone who is not on the research team
from knowing that you provided this information, or what that information is. The
consent forms with signatures will be kept separate from the information we collect,
which will not include names and which will be presented to others only when combined
with other responses. Although we will make every effort to protect your confidentiality,
there is a low risk that this might be breached.
IN THE EVENT OF A RESEARCH-RELATED INJURY
In the event of injury resulting from your participation within this study, treatment can be
obtained at a health care facility of your choice. You should understand that the costs of
such treatment will be your responsibility. Financial compensation is not available
through The University of Toledo or The University of Toledo Medical Center.
In the event of an injury, contact Dr. Barry Scheuermann, PhD at (567) 288-9732, Trent
Cayot, BS, CSCS at (937) 441-2191, or Jakob Lauver, MS, CSCS at (517) 902-3558.
VOLUNTARY PARTICIPATION
Taking part in this study is voluntary. You may refuse to participate or discontinue
participation at any time without penalty or a loss of benefits to which you are otherwise
entitled. If you decide not to participate or to discontinue participation, your decision
will not affect your future relations with the University of Toledo or The University of
Toledo Medical Center.
NEW FINDINGS
You will be notified of new information that might change your decision to be in this
study if any becomes available.
OFFER TO ANSWER QUESTIONS
Before you sign this form, please ask any questions on any aspect of this study that is
unclear to you. You may take as much time as necessary to think it over. If you have
questions regarding the research at any time before, during or after the study, you may
contact Dr. Barry Scheuermann (419-530-2692) or Trent Cayot
([email protected]).
If you have questions beyond those answered by the research team or your rights as a
research subject or research-related injuries, please feel free to contact the Chairperson of
the University of Toledo Biomedical Institutional Review Board at 419-383-6796.
SIGNATURE SECTION (Please read carefully)
YOU ARE MAKING A DECISION WHETHER OR NOT TO PARTICIPATE IN THIS
RESEARCH STUDY. YOUR SIGNATURE INDICATES THAT YOU HAVE READ
THE INFORMATION PROVIDED ABOVE, YOU HAVE HAD ALL YOUR
141
QUESTIONS ANSWERED, AND YOU HAVE DECIDED TO TAKE PART IN THIS
RESEARCH.
BY SIGNING THIS DOCUMENT YOU AUTHORIZE US TO USE OR
DISCLOSE YOUR PROTECTED HEALTH INFORMATION AS DESCRIBED IN
THIS FORM.
The date you sign this document to enroll in this study, that is, today’s date, MUST fall
between the dates indicated on the approval stamp affixed to the bottom of each page.
These dates indicate that this form is valid when you enroll in the study but do not reflect
how long you may participate in the study. Each page of this Consent/Authorization
Form is stamped to indicate the form’s validity as approved by the UT Biomedical
Institutional Review Board (IRB).
142
Appendix F
JOHN WILEY AND SONS LICENSE TERMS AND CONDITIONS
This Agreement between Trent E Cayot ("You") and John Wiley and Sons ("John Wiley and
Sons") consists of your license details and the terms and conditions provided by John Wiley
and Sons and Copyright Clearance Center.
License Number
3595950016829
License date
Mar 25, 2015
Licensed Content
John Wiley and Sons
Publisher
Licensed Content
Clinical Physiology and Functional Imaging
Publication
Licensed Content
Effects of blood flow restriction duration on muscle activation and
Title
microvascular oxygenation during low-volume isometric exercise
Licensed Content
Trent E. Cayot, Jakob D. Lauver ,Christopher R. Silette, Barry W.
Author
Scheuermann
Licensed Content
Jan 7, 2015
Date
Pages
1
Type of use
Dissertation/Thesis
Requestor type
Author of this Wiley article
Format
Print and electronic
Portion
Full article
Will you be
No
translating?
Title of your thesis / The Effect of Blood Flow Restriction Techniques during Aerobic
dissertation
Exercise in Healthy Adults
Expected completion
May 2015
date
Expected size
110
143
(number of pages)
Requestor Location
Billing Type
Billing Address
Total
Trent E Cayot
2801 W Bancroft St
Mail Stop 119
Department of Kinesiology
TOLEDO, OH 43606
United States
Attn: Trent E Cayot
Invoice
Trent E Cayot
2801 W Bancroft St
Mail Stop 119
Department of Kinesiology
TOLEDO, OH 43606
United States
Attn: Trent E Cayot
0.00 USD
144
Appendix G
Curriculum Vitae
Trent Cayot
Educational Background
08/2011 – 05/2015
Toledo, Ohio
The University of Toledo




08/2007 – 05/2011
Toledo, Ohio
Doctor of Philosophy (Ph.D.) Degree in Exercise
Science
Concentration: Exercise Physiology
College: College of Graduate Studies, College of
Health Sciences
Dissertation Title: The Effect of Blood Flow
Restriction Techniques during Aerobic Exercise in
Healthy Adults
The University of Toledo





Honorary Bachelor’s of Science (B.S.) Degree in
Exercise Science
Concentration: Exercise Science
College: Honor’s College, Health Science & Human
Services
Institutional Honors: Honors, Cum Laude
Thesis Title: Electromyography Analysis of Functional
Suspended Elbow Flexion Curls Vs. Standard Elbow
Flexion Curls
145
Employment Experience
08/2011 – 05/2015
Toledo, Ohio
The University of Toledo
06/2011 – 07/2015
Toledo, Ohio
Promedica Health Systems Wildwood Orthopaedic & Spine
Hospital, Wildwood Athletic Club & Promedica Wellness





10/2007 – 08/2011
Toledo, Ohio
Position: Certified Strength & Conditioning Specialist
(CSCS)
Programs:
o Sports Medicine (M.D.) Fellowship Exercise
Physiology Lecture Series
o Executive Health Physicals (Stress Test &
Fitness Evaluation)
o Design and implementation of exercise
programs for healthy, athletic, and clinical
populations (Age Management, eXcel Sports
Performance, & Script 4 Fitness)
The University of Toledo



06/2007 – 01/2008
Bellefontaine, Ohio
Position: Graduate (Teaching) Assistant
College: College of Health Science
Department: Department of Kinesiology
Positions: Undergraduate Assistant (UGA), Certified
Personal Trainer (CPT), and Student Wellness and
Awareness Team (SWAT) Facilitator
Office: Office of Recreation
Department: Wellness Center
Mary Rutan Rehabilitation Center


Position: Physical Therapy Technician
Responsibilities: Therapeutic resistance training,
ultrasound treatments, general maintenance and office
duties.
146
Teaching Experience
The University of Toledo (Toledo, Ohio)
 KINE 3830 - Principles of Strength and Conditioning (Lecture & Lab)
 KINE 3820 - Sports Medicine for Coaches (Provided Assistance to
Instructor)
 KINE 2540 - Human Physiology Lab
 KINE 2470 - Human Anatomy & Physiology Lab II
 KINE 2460 - Human Anatomy & Physiology Lab I
 Blackboard +Learn (On-Line Teaching Platform)
ProMedica Health Systems (Toledo, Ohio)
 Sports Medicine (M.D.) Fellowship Exercise Physiology Lecture Series
(Lecture & Lab)
 Strength/Conditioning & Health/Fitness Webinars
Professional Awards
University of Toledo College of Health Sciences Interprofessional Graduate Research
Award (2015)
Title: The Effects of Blood Flow Restriction Interval Training on Aerobic
Capacity and Muscular Strength
American Kinesiotherapy Association (AKTA) John Eisele Davis Memorial Award
(2014)
Distinguished Service in the Field of Physical Medicine and Rehabilitation
University of Toledo Graduate Student Association Graduate Research Award (2013)
Title: The Acute Effects of Vascular Occlusion during Sub-Maximal Endurance
Exercise
Award Total: $1,995
Peer-Review Publications
JOURNAL ARTICLES
Cayot TE, Lauver JD, Silette CR, Scheuermann BW. Effects of blood flow restriction
duration on muscle activation and microvascular oxygenation during low-volume
isometric exercise. Clinical Physiology and Functional Imaging (Ahead of Print).
Lauver JD, Cayot TE, Scheuermann BW. Influence of bench angle on upper extremity
neuromuscular activation during bench press exercise. European Journal of Sport
Science (Ahead of Print).
147
ABSTRACTS
Cayot TE, Shaw AP, Silette C, Scheuermann BW. The effect of blood flow restriction
during sub-maximal endurance exercise. Medicine & Science in Sports & Exercise.
46(5): S203, 2014.
Lauver JD, Cayot TE, Scheuermann BW. The influence of suspension training on
neuromuscular recruitment patterns. Medicine & Science in Sports & Exercise. 46(5):
S516, 2014.
Cayot TE, Shaw AP, Silette C, Garmyn EC, Scheuermann BW. Effects of blood flow
restriction exercise during isometric contractions on neuromuscular recruitment
patterns. Journal of Strength and Conditioning Research. 27(Suppl 2): S12, 2013.
Kruse NT, Cayot TE, Fosnaugh AG, Garmyn EC, McGlinchy SA, Scheuermann, BW.
Pulmonary O2 uptake and muscle deoxygenation responses to repeated bouts of fast ramp
exercise. Medicine & Science in Sports & Exercise. 44(Suppl 2): 558, 2012.
Cayot TE, Schick E, Gochiocco M, Wambold S, Stacy M, Scheuermann BW.
Electromyographic analysis of suspension elbow flexion curls and standard elbow flexion
curls. Medicine & Science in Sports & Exercise. 43(5): S272-S273, 2011.
Professional Research Presentations
42nd Annual Midwest Chapter American College of Sports Medicine Meeting
 Date: November, 2014 (Merrillville, Indiana)
 Free Communication: The effects of acute blood flow restriction interval
training on aerobic capacity and maximal strength
61st Annual American College of Sports Medicine Meeting
 Date: May 2014 - June 2014 (Orlando, Florida)
 Poster Presentation: The effect of blood flow restriction during submaximal endurance exercise
41st Annual Midwest Chapter American College of Sports Medicine Meeting
 Date: November, 2013 (Merrillville, Indiana)
 Poster Presentation: The effect of blood flow restriction during submaximal endurance exercise
36th Annual National Strength & Conditioning Association National Conference
 Date: July 2013 (Las Vegas, Nevada)
 Poster Presentation: Effects of blood flow restriction exercise during
isometric contractions on neuromuscular recruitment patterns
148
58th Annual American College of Sports Medicine Meeting
 Date: May 2011 – June 2011 (Denver, Colorado)
 Poster Presentation: Electromyography analysis of functional suspended
elbow flexion curls vs. standard elbow flexion curls
Professional Certifications & Memberships
National Strength and Conditioning Association (NSCA)
Certified Strength and Conditioning Specialist (CSCS)
National Student Member (February 2012 - Present)
American College of Sports Medicine (ACSM)
National Student Member (November 2012 - Present)
Midwest Regional Student Member (October 2013 - Present)
The American Physiological Society
National Student Member (April 2013 – Present)
American Heart Association
Healthcare Provider Basic Life Support (BLS)
Fitness Anywhere Inc
Certified Suspension Trainer – Level 1 (STC)
Sports Medicine Certified Suspension Trainer – Level 2 (SMSTC)
Volunteer Services
National Strength and Conditioning Association (April 2015 – Present)
Position: Ohio State Advisory Board Member
College of Health Sciences Honor's Scholarship & Experience Day Volunteer
Department: Department of Kinesiology
Position: Hands-On Equipment Demonstrations
Techniques: Three Dimensional Motion Capture, Surface Electromyography
(EMG)
University of Toledo Research Strategic Planning Committee
College: Judith Herb College of Education, Health Science Human Services
Position: Graduate Student Committee Member
University of Toledo Club Hockey Team
Department: Office of Recreation, Wellness Center
Position: Volunteer Strength and Conditioning Coach
149