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Journal of Exercise Physiologyonline
June 2017
Volume 20 Number 3
Official Research Journal of
Editor-in-Chief
the American
Society
of
Tommy
Boone, PhD,
MBA
Exercise
Physiologists
Review
Board
Todd Astorino, PhD
ISSN 1097-9751
Julien Baker,
PhD
Steve Brock, PhD
Lance Dalleck, PhD
Eric Goulet, PhD
Robert Gotshall, PhD
Alexander Hutchison, PhD
M. Knight-Maloney, PhD
Len Kravitz, PhD
James Laskin, PhD
Yit Aun Lim, PhD
Lonnie Lowery, PhD
Derek Marks, PhD
Cristine Mermier, PhD
Robert Robergs, PhD
Chantal Vella, PhD
Dale Wagner, PhD
Frank Wyatt, PhD
Ben Zhou, PhD
Official Research Journal
of the American Society of
Exercise Physiologists
ISSN 1097-9751
JEPonline
Effects of Physical Exercise on an Amazonian
Population with Chronic Obstructive Pulmonary
Disease in Autonomic Heart Rate Modulation
Rodrigo Rocha1,2,3, Edivânia Silva3, Jairo Conceição 3, Larissa
Rocha 3, Saul Carneiro4, Marlene A. Moreno1
1Postgraduate
Program of Sciences of Human Movement of
Methodist University of Piracicaba, São Paulo, Brazil, 2Department of
Sciences of Human Movement of State University of Pará, Pará,
Brazil, 3School of Physiotherapy of Amazon University, Pará, Brazil
4University Hospital João de Barros Barreto/Federal University of
Pará, Pará, Brazil
ABSTRACT
Rocha R, Silva E, Conceição J, Rocha L, Carneiro S, Moreno M.
Effects of Physical Exercise on an Amazonian Population with
Chronic Obstructive Pulmonary Disease in Autonomic Heart Rate
Modulation. JEPonline 2017;20(3):156-167. The aim of this study
was to verify the effect of an exercise protocol on the autonomic
modulation of the heart rate of individuals with chronic obstructive
pulmonary disease. Thirty-three of the initial 38 subjects with chronic
obstructive pulmonary disease (COPD) completed the study. Heart
rate variability (HRV) was evaluated using the POLAR® monitor. All
subjects performed aerobic physical training and muscle
strengthening. Rehabilitation occurred for 8 wks with 2 sessions·wk-1
lasting 50 min each. The variables in time domain (R-R interval,
SDNN, RMSSD, and TINN), in frequency domain (LF, HF, and
LF/HF), and nonlinear variables (SD1, SD2, Shannon Entropy, and
Determinism) were analyzed. The findings indicate that in the
frequency domain of variability, no variables were statistically
significant. However, the RMSSD, SD1, and SD2 indices presented
significant results after pulmonary rehabilitation, which positively
influenced the autonomic modulation of the heart rate of COPD
patients.
Key Words: Autonomic Nervous System, Chronic Obstructive
Pulmonary Disease, Rehabilitation
157
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is due to an inflammatory response that
leads to respiratory muscle dysfunction that plays a key role in gas exchange abnormalities. It
is associated with smoking and/or exposure to harmful airways (16). In the Brazilian Amazon,
the effects of biomass burning on lung function and the development of respiratory diseases
is still a relatively new area of study (34). However, it is clear that individuals with COPD have
reduced peak expiratory flow, which is a condition that is also associated with quality of air
(35) and living in cities around the arch of deforestation (such as Belém-Pará) (8).
Among the symptoms of COPD are dyspnea, nutritional changes, decreased strength of the
muscular system (especially the muscles involved in respiratory function), low exercise
capacity due to the muscle weakness and fatigue, and pulmonary hyperinflation (12), which
may also be related to the alteration of autonomic heart rate modulation. One or more of
these conditions will reduce the physical conditioning of the COPD population, making
pulmonary rehabilitation essential in these patients (23) to help avoid the increased risk for
repeated hospital admissions (33).
Pulmonary rehabilitation protocols tend to improve the COPD patient’s response to physical
exercise and barroreflex performance. In addition, the rehabilitation protocols help to improve
the patient’s autonomic heart rate modulation from the attenuation of dyspnea. The overall
result is that the improvements help to produce a better chest mobilization with a positive
influence on the sympathetic nervous system (31).
Patients with COPD have chronic characteristics that lead to several impairments in their
autonomic function and intolerance to physical activities (14). Thus, the purpose of the
present study was to verify the effect of a pulmonary rehabilitation with an exercise protocol
on the autonomic modulation of the heart rate of individuals with COPD in Brazilian Amazon.
METHODS
Subjects
This study consisted of 38 volunteers with a clinical diagnosis of severe and very severe
COPD. All subjects met the inclusion criteria to participate in this study. Volunteers with
deformities, hemodynamic instability, cardiovascular diseases, uncontrolled hypertension,
and beta pacemakers, and those who were diagnosed with associated diseases that could
interfere with cardiac autonomic control or impede exercise tolerance were not considered for
this study.
The study was conducted in the physiotherapy outpatient clinic of the University Hospital
João de Barros Barreto between January 2016 and February 2017. The research was
approved by the Research Ethics Committee of the University Hospital João de Barros
Barreto under the number of opinion 1.322.578, with clinical trial registration in the Clinical
Trials NCT02783326, as well as the agreement and signing of the Informed Consent Form by
the volunteers before starting the study.
158
Procedures
All subjects had the same clinical prognosis with a similar degree of pulmonary dysfunction. It
was an experimental and non-randomized clinical study that used physical training according
to the criteria established by the Global Initiative for Chronic Obstructive Pulmonary Disease
(GOLD) (14). Rehabilitation (i.e., aerobic training, muscle strengthening, and stretching of the
involved muscles) was 8 wks in duration with 2 sessions·wk-1 for ~50 min each session.
During each pulmonary rehabilitation session, the patients engaged in 20 min of aerobic
training on a treadmill and/or exercise bicycle with a modified Borg effort perception scale at
a tolerable intensity level of 4. Then, the patients worked on increasing muscle strength of
their upper limbs using dumbbells, elastic bands, and open and closed kinetic chains
exercises. Each session ended with the patients doing active stretching exercises.
Strength training consisted of 3 sets of 10 repetitions for each exercise. The load imposed
was 1 kg for each subject to which the subject performed movements of diagonal upper
limbs, as well as flexion and extension of the lower limb, adding 1 kg every 1 min until
maximum effort was achieved. The strength treatment consisted of 50% of the maximum load
of which the test was repeating every 2 wks for progression of the load.
The evaluation of heart rate variability (HRV) was performed one day before the start of the
pulmonary rehabilitation protocol and 24 hrs at the end of the protocol to avoid the influence
of physical exercise on the autonomic frequency modulation of the heart (11). The VFC was
captured by means of a frequency meter of the POLAR® brand, model RS800cx. The heart
rate signal was captured by a strap placed on the subjects’ chest at the xiphoid process while
lying supine for 10 min. Subjects were instructed to maintain a normal breathing pattern. No
talking was permitted so that the heart rate did not change. The data were transferred to a
researcher who was not involved in the present study. The researcher transferred the data to
the Polar®ProTrainer Software through an infrared signal transmission interface, which
transformed into .txt text format so that it could be analyzed by a mathematical routine in the
Kubios® HRV2.2 program to obtain each subject’s heart rate variability. Then, the data were
tabulated in the Excell program to perform the statistical analysis. All subjects were identified
by codes.
Statistical Analyses
The BioEstat® 5.2 application was used for statistical analysis. The Shapiro-Wilk test was
used to verify the distribution of the data. The Student's t-test was used for the analysis of
significance. For the nominal variables, the Binominal test was used. Statistical significance
was set at an alpha level of P<0.05. The data are presented as mean and standard deviation.
RESULTS
Thirty-eight subjects (27 males and 11 females) with a mean age 67.94 ± 8.49 yrs were
initially enrolled in the study. However, due to different reasons, 33 subjects with COPD
completed the study. The flowchart of the study volunteers is shown in Figure 1. The
demographic and clinical data are presented in Table 1 and Table 2.
159
Enrollment
Assessed for eligibility (n=38)
Excluded
¨ Refused participation (n=1)
Allocation
Exercise protocol (n=37)
Follow-Up
Excluded
Desistence (n=3)
Hospitalization (n=1)
Analysed (n=33)
Analysis
Figure 1. Participation Flowchart of the Subjects in the Study.
Table 1 presents the mean values and standard deviations of the subjects’ age, body mass
index (BMI), and forced expiratory volume in the first second (FEV1). Blood pressure (systolic
and diastolic pressures), respiratory rate (RF), and frequency (HR) at rest before and after
the application of pulmonary rehabilitation protocol were also measured, but are not
presented in the Table.
160
Table 1. Demographic and Clinical Characteristics of the Subjects with Values
Expressed as Means and Standard Deviations.
Categories
Mean ± SD
Age
BMI (kg·m-²)
FEV1
68.46 ± 8.27
21.90 ± 3.68
4.67 ± 11.79
BMI = body mass index; FEV1 = Forced expiratory volume in the first second
Table 2 shows that ~80% of the subjects were smokers, and that the minority (i.e., 15.3%)
needed oxygen supplementation in the treatment, as well as the predominance of subjects in
the severe stage of COPD. In addition, the drugs bromide tiotropium (a long acting, 24-hr
anticholinergic bronchodilator), salmeterol xinafoate (used with other medicines to treat
bronchospasms), and fluticasone propianate (an oral inhaler used to manage asthma) were
the most commonly used by the subjects, with more than 50% of the sample using additional
drugs concomitant with them.
Table 2. Clinical Characteristics of Subjects.
Variables
Stage of Disease
Severe
Very severe
Drugs
Bromide Tiotropium
Salmeterol Xinafoate
Fluticasone Propionate
Subject Percentage
84.6
15.4
84.6
76.9
53.8
Smoking
Yes
76.9
No
23.1
Oxygen Therapy
Yes
15.3
No
84.7
Comorbidities
Hypertension
Diabetes Mellitus
53.8
7.6
As shown in Table 3, in regards to the linear variables in the time domain, only the RMSSD
index was significant (P≤0.05). In the frequency domain, no significant variable was found.
Regarding the nonlinear indices, the dispersion of points perpendicular to the line of identity
161
(SD1) and the dispersion of points along the line of identity (SD2) presented significant
results.
Table 3. Analysis of Pre- and Post-Pulmonary Rehabilitation Variables with Values
Expressed as Means and Standard Deviations.
Variables
RR (ms)
SDNN (ms)
RMSSD (ms)
TINN (ms)
LF (nu)
HF (nu)
LF/HF
SD1 (ms)
SD2 (ms)
Det (%)
SE
Pre-Program
Post-Program
P Value
786.3 ± 130.74
27.03 ± 15.28
19.90 ± 15.09
135 ± 85.07
63.73 ± 25.45
36.26 ± 25.45
3.8 ± 4.0
14.13 ± 10.71
36.34 ± 20.67
97.83 ± 1.75
3.1 ± 3.02
761.10 ± 129.56
24.43 ± 14.39
20.76 ± 20.70
114.61 ± 64.14
54.79 ± 25.82
45.20 ± 25.82
2.2 ± 3.1
14,76 ± 14.75
30.98 ± 16.76
97.84 ± 1.48
3.1 ± 3.2
0.0653
0.0555
0.0095*
0.0989
0.1390
0.1425
0.1731
0.0031*
0.0032*
0.0896
0.1815
RR = R-R interval (R-Ri); SDNN = Standard deviation of the mean of the normal iR-R; RMSSD =
Square root of the mean square of the differences between consecutive iR-Rs; TINN = Triangular
interpolation of RR intervals; LF = Low frequency; HF = High Frequency; LF/HF = Ratio between low
frequency and high frequency; SD1 = Dispersion of points perpendicular to the line of identity; SD2 =
Dispersion of points along the identity line; Det = Determinism; SE = Entropy Shannon; Normalized
Units (nu); Milliseconds (ms). *P≤0.05
DISCUSSION
The purpose of this study was to evaluate the effects of exercise in patients with COPD on
cardiac autonomic modulation. A number of studies have tested the effects of exercise on
heart rate variability in COPD (15,32), but none has tested in Amazonian population with
COPD.
The demographic characteristics presented by Handa et al. (15) and Vasiliki et al. (32)
indicate the prevalence of males with COPD. Also, the data presented by Azambuja et al. (2)
report that active smoking is the primary cause of the disease. This is a pathology that first
affected the male gender, reflecting the increase in the mortality rate among men. However, it
is important to point out that women may be more susceptible to cigarette smoke and more
likely to develop COPD than previously realized. In the United States, COPD in women is
actually higher in every age group except for people older than 74, which is in contrast to
Brazil.
The subjects in the present study were classified as having low body weight, which is in
agreement with the BMI analysis as reported by Costa et al. (10). They explained that
162
patients with COPD usually present changes in their body composition that are associated
the loss of lean muscle mass, the presence of sarcopenia, and physical intolerance to
exercise and daily physical activities. In addition to the subjects’ mean age of 68 yrs and no
regular exercise, the physiological deterioration (18) may explain why the subjects struggled
to perform everyday activities such as walking and performing basic self-care. Also, for these
reasons, there is an increase in the risk of mortality in people with COPD.
The prevalence of smokers in the present sample is notorious, since smoking is indicated as
the main risk factor for COPD (27). However, this pathology may also occur by genetic
etiology, such as alpha-1-antitrypsin deficiency; whereas it is responsible for the regulation of
elastase synthesis that plays a protective role in the lungs in the presence of inflammation or
irritants (16). This may explain the presence of non-smokers with a diagnosis of COPD in the
present study.
Regarding the presence of comorbidities, studies have demonstrated a strong relationship
between the metabolic syndrome and COPD. This indicates that such an association may be
due to the continuous inflammatory response presented in COPD, where in response to
inflammatory changes the immune system ends up performing metabolic compensations that
may lead to hyperlipidemia and increased gluconeogenesis that predisposes an individual to
cardiovascular alterations or even diabetes mellitus (1,34).
It is noteworthy that 53.8% of subjects in this study had high blood pressure. The presence of
this comorbidity is not uncommon among COPD patients, which is in agreement with the
findings of Simonovska et al. (27). Mazzocchi et al. (19) when analyzing the behavior of the
physiological variables of the COPD patients submitted to a walking test of 6 min followed by
a ladder test to verify that the patients’ HR change occurs due to the variation of load during
the rehabilitation protocol. Lung damage from the disease causes the heart to work harder to
send blood and oxygen to the musculature.
According to GOLD (14), drug therapy is an important treatment in the different stages of
COPD. In fact, in the present study, 84.6% of the subjects were taking bromide triotropium.
Baker et al. (3), it is associated with a decrease in the occurrence of exacerbation of the
disease when compared to placebos. Approximately 77% of the subjects were taking
salmeterol xinafoate and ~54% were taking fluticasone propionate; both medications help to
decrease the number of deaths from COPD (26).
Oxygen therapy, also known as supplementary oxygen therapy, is a common medical
treatment that has been shown to prolong life in COPD patients with severe resting
hypoxemia. Also, in cases of desaturation during physical activities by individuals with COPD,
oxygen therapy helps to ensure that an adequate amount of oxygen is attached to
hemoglobin in the blood that is pumped by the heart to all tissues of the body. The fact that
only 15.3% of the subjects in the present study were using supplementary oxygen therapy
indicates that they were not in the very serious state of the disease (22).
The population affected by COPD usually presents with a sympathetic hyperactivity that can
be explained by the increase of norepinephrine levels in the blood plasma as well as the
association with cardiac arrhythmias, atrial fibrillation, ventricular tachycardia, and myocardial
infarction. Therefore, studies suggest that the increase of the catecholamines levels of the
163
COPD patients end up contributing to their clinical characteristics, particularly since the
sympathetic function tends to prevail over the parasympathetic even after the application of a
physical training program. This point of view helps in understanding the non-significance of
some variables that were analyzed during the current study (13).
The present study evaluated the HRV through linear and nonlinear indexes of the COPD
subjects, and as such the evaluations give rise to results regarding the behavior of the
autonomic function of the subjects (21). However, while little is explained in the literature with
the linearity data, the data on nonlinear HRV analysis is considered the most reliable method
for such assessment (6), so much so that Santana et al. (25) confirmed such thinking. As
such then, the nonlinear evaluation performed in the present study was the index SD1 of
which Carvalho et al. (9) observed that the SD1 values are lower in individuals with COPD
compared to healthy individuals and that because this index indicates the parasympathetic
influence on the sinoatrial nodule, its decrease implies a reduction in vagal action in COPD
patients. In support of the pulmonary rehabilitation protocol, the present study showed a
better parasympathetic performance because the subjects presented higher SD1 values of
this index which were statistically significant after compared to the pre-treatment data.
Regarding the linear analysis, the RMSSD index collected in the time domain during the
research, presented statistical significance in the results. Because this variable represents
the behavior of the parasympathetic nervous system (31), what is commonly observed are
smaller values for this variable when comparing individuals with COPD and healthy (23).
However, the present study reports higher values of RMSSD in patients with COPD after the
pulmonary rehabilitation protocol, thus indicating the effect of physical training on
parasympathetic performance. This is a condition favorable to this population since COPD
patients tend to present sympathetic exacerbation (30). Corroborating with the present study,
when analyzing the HRV of individuals with COPD immediately and after 5,10, and 15 min of
resistance exercise with intensities of 60% and 90% of a maximal repetition, Nicolino et al.
(22) observed that during recovery,the subjects’ heart rate returned with readjustment of the
vagal sympathetic relation, ue to the parasympathetic reactivation reached. The prolongation
of these effects, even after the cessation of the exercises, will provide an increase in the
variation of the RR intervals.
Regarding the training time, Borghi-Silva and colleagues (4) when comparing the effect of 6
and 12 wks of physical training on patients with pulmonary obstructive disease, the
improvement in both autonomic function and functional capacity in the first 6 (SDSS, SD2,
and entropy), but after 12 weeks of training there was a further improvement in the SD1 index
compared to the first 6 wks of initial training. This study was shown analogous to the current
study, since the sample was submitted to a physical treatment of 8 wks. It can soon be
concluded that the time of pulmonary rehabilitation protocol application interferes with the
HRV SD2 index, a fact that can be shown in the present study. A significant increase of the
parasympathetic function in the high-frequency variable of the autonomic modulation of
patients with COPD was observed in the results of the research conducted by Leite et al. (18)
after the application of a 12-wk aerobic training. Thus, it is very likely that the analysis of HRV
in the frequency domain in the present study was not significant due to the fact that it had a
duration and weekly frequency less than the studies by Borghi-Silva et al. (4) and Leite et al.
(18).
164
Borghi-Silva et al. (5) verified the effectiveness of a 6-wk aerobic training on the HRV of
volunteers with COPD and found a reduction in sympathetic hyperactivity both during
submaximal activity and at rest, assuming that such effect is linked to a decrease in levels of
catecholamines and/or anxiety. These benefits may have occurred in the sample of the
present study, since they underwent aerobic training and presented better sympatho-vagal
control.
There are just a few studies in the literature that report significant changes in the SDNN index
analysis of the autonomic modulation of COPD patients after muscular strength training,
which is not that different from the results reported in the present study. Yet, Camillo et al.
(7), reported significance in such variable proposed after a high-intensity protocol with a
duration of 3 months. In contrast their study, the present study represents a small number of
moderate intensity muscle training sessions.
CONCLUSIONS
The pulmonary rehabilitation protocol used in this study, which contains both aerobic and
resistance exercises, positively influenced the autonomic modulation of the COPD patients’
heart rate of the Brazilian Amazon. The findings highlight the alterations achieved in the
nonlinear HRV analysis, which is still the method of evaluation performed in clinical practice
to making a better understand the functioning of the body systems. Thus, it is suggestive that
this same population be submitted to a longer treatment period in order to achieve better
results; a fact that may lead to the modification of other important variables in autonomic
heart rate modulation.
Address for correspondence: Rodrigo Rocha, Department of Sciences of Human Movement,
State University of Pará, Belém, Pará, Brazil, 66087-670, Email: [email protected]
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