J Appl Physiol 104: 97–102, 2008.
First published October 4, 2007; doi:10.1152/japplphysiol.00608.2007.
Anaerobic and aerobic relative contribution to total energy release during
supramaximal effort in patients with left ventricular dysfunction
Alessandro Mezzani,1 Ugo Corrà,1 Cristina Andriani,1 Andrea Giordano,2 Roberto Colombo,2
and Pantaleo Giannuzzi1
1
Cardiology Division, and 2Bioengineering Service, Salvatore Maugeri Foundation, Veruno Scientific Institute, Veruno, Italy
Submitted 6 June 2007; accepted in final form 3 October 2007
heart failure; exercise; maximal accumulated oxygen deficit; peak
oxygen uptake; energetic metabolism
EXERCISE ENERGETIC METABOLISM is impaired in patients with left
ventricular dysfunction in both cardiac and skeletal muscle (4,
19). Aerobic energy release at peak exercise (V̇O2peak) is
classically reduced (2), and its evaluation has become part of
the routine clinical assessment of these patients, since the
degree of its reduction is a strong prognostic marker (15). On
the contrary, anaerobic metabolic pathways have received less
attention. In patients with left ventricular dysfunction, anaerobic energetic release during exercise has been evaluated only in
effort intensity domains below V̇O2peak (10, 20, 25, 27), but no
data are available on the anaerobic energetic yield during
Address for reprint requests and other correspondence: A. Mezzani, S.
Maugeri Foundation, Veruno Scientific Institute, IRCCS, Cardiology Division,
Laboratory for the Analysis of Cardiorespiratory Signals, Via per Revislate,
13, 28010 Veruno (NO), Italy (e-mail: [email protected]).
http://www. jap.org
supramaximal effort, i.e., above V̇O2peak, which would describe
the true anaerobic metabolism energetic potential. More importantly, a simultaneous evaluation of maximal activation of
both anaerobic and aerobic systems would examine the anaerobic/aerobic interaction under conditions of maximal stress.
We recently proposed the maximal accumulated oxygen
deficit (MAOD) as a descriptor of the maximal amount of
energy obtainable from anaerobic metabolism in stable chronic
heart failure patients (20) and demonstrated the safety of its
determination in this population. This makes it possible to
directly measure maximal anaerobic energy release in the
effort supramaximal domain, i.e., at powers evoking by definition V̇O2peak (34), offering for the first time the possibility to
simultaneously evaluate the maximal activation of both anaerobic and aerobic metabolic systems and obtain a complete and
coherent description of exercise energetic metabolism in patients with left ventricular dysfunction.
The aim of the present study was thus to apply the abovementioned findings to the evaluation of the relative anaerobic
vs. aerobic contribution to total energy release during supramaximal effort in patients with symptomatic and asymptomatic
left ventricular dysfunction and to compare it with that of an
age-matched group of normal subjects to gain new insight into
left ventricular dysfunction exercise pathophysiology.
METHODS
Study population. We studied 19 male patients with left ventricular
dysfunction (Dysf) and 17 normal male subjects. Patients were selected according to the following criteria: 1) history of ischemic or
idiopathic dilated cardiomyopathy with or without symptoms and
clinical episodes of heart failure; 2) echocardiographic left ventricular
ejection fraction of ⱕ40%; 3) cardiopulmonary exercise test (CPX)
stopped for fatigue and/or dyspnea with ventilatory anaerobic threshold (VAT) identification and peak respiratory exchange ratio of
ⱖ1.10; 4) absence of angina and/or instrumentally inducible myocardial ischemia and/or evidence of complex ventricular arrhythmias; 5)
stable medications with no exacerbation of symptoms or need for
intravenous inotropic support in the 6 mo before assessment. Thirteen
Dysf had a history of chronic heart failure (New York Heart Association class I–II), whereas the remaining six did not. All patients
underwent an echocardiographic evaluation within 5 ⫾ 2 days of the
baseline CPX. Recruitment criteria for normal subjects (N) were 1) no
history of cardiac or noncardiac disease; 2) normal resting ECG; 3)
CPX stopped for fatigue and/or dyspnea with VAT identification and
peak respiratory exchange ratio of ⱖ1.10.
The protocol was approved by the Central Ethics Committee of the
S. Maugeri Foundation, and informed, written consent was obtained
from all participants in the study.
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked “advertisement”
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
8750-7587/08 $8.00 Copyright © 2008 the American Physiological Society
97
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Mezzani A, Corrà U, Andriani C, Giordano A, Colombo R,
Giannuzzi P. Anaerobic and aerobic relative contribution to total energy
release during supramaximal effort in patients with left ventricular dysfunction. J Appl Physiol 104: 97–102, 2008. First published October
4, 2007; doi:10.1152/japplphysiol.00608.2007.—Energetic metabolism
during effort is impaired in patients with left ventricular dysfunction
(Dysf), but data have been lacking up to now on the relative anaerobic
vs. aerobic contribution to total energy release during supramaximal
effort. Recently, the maximal accumulated oxygen deficit (MAOD)
has been shown to be measurable in Dysf patients, making it possible
to evaluate the anaerobic/aerobic interaction under conditions of
maximal stress of both anaerobic and aerobic metabolic pathways in
this population. Nineteen Dysf patients and 17 normal patients (N)
underwent one ramp cardiopulmonary, three moderate-intensity constant-power, and three supramaximal constant-power (1- to 2-min, 2to 3-min, and 3- to 4-min duration) exercise tests. MAOD was the
difference between accumulated O2 demand (accO2dem; estimated
from the moderate-intensity O2 uptake/watt relationship) and uptake
during supramaximal tests. Percent anaerobic (%Anaer) and aerobic
(%Aer) energetic release were [(MAOD/accO2dem) 䡠 100] and 100 ⫺
%Anaer, respectively. MAOD did not vary between 1–2, 2–3, and
3– 4 min supramaximal tests, whereas accO2dem increased significantly with and was linearly related to test duration in both Dysf and
N. Consequently, %Anaer and %Aer decreased and increased, respectively, with increasing test duration but did not differ between Dysf
and N in 1–2 min, 2–3 min, and 3– 4 min tests. Our study demonstrates a similar relative anaerobic vs. aerobic contribution to total
energy release during supramaximal effort in Dysf and N. This finding
indicates that energetic metabolism during supramaximal exercise is
exercise tolerance independent and that relative anaerobic vs. aerobic
contribution in this effort domain remains the same within the physiology- or pathology-induced limits to individual peak exercise performance.
98
EFFORT ENERGY RELEASE IN LEFT VENTRICULAR DYSFUNCTION
冤冢兺
n
MAOD (ml/kg) ⫽ [(estV̇O2/60) 䡠 T] ⫺
i⫽1
冣冥
measV̇O2i /60 䡠 t
(1)
where estV̇O2 is expressed in milliliters per kilogram per minute, T is
test duration expressed in seconds, n is the number of 10-s periods
composing the exercise phase, measV̇O2 is the V̇O2 mean value for
each 10-s period expressed in milliliters per kilogram per minute, and
t is equal to 10 s. Because patients and subjects did not reach
exhaustion at precise 10-s intervals, the measV̇O2 of the last 10-s
J Appl Physiol • VOL
interval of the exercise period (i.e., that containing the residual
exercise seconds) was divided by 60 and then multiplied by the
number of residual seconds, and the result was added to measured
accumulated V̇O2.
Percent anaerobic (%Anaer) and aerobic (%Aer) contributions to
total energy release were then calculated as follows:
%Anaer ⫽ {MAOD/[(estV̇O2/60) 䡠 T]} 䡠 100
(2)
%Aer ⫽ 100 ⫺ %Anaer
(3)
Brain-natriuretic peptide level evaluation. At the beginning of the
study protocol, in all Dysf patients, a blood sample was collected by
venipuncture into EDTA tubes, kept at room temperature, and analyzed within 15 min of the draw time. Before analysis, each tube was
turned upside down several times to ensure homogeneity. Brainnatriuretic peptide (BNP) was measured by using a fluorescence
immunoassay for the quantitative determination of BNP in whole
blood and plasma specimens (Triage BNP Test; Biosite, San Diego,
CA).
Statistics. Unpaired t-tests were used to compare the means of
quantitative variables. Linear regression and Pearson’s product-moment coefficients were used to determine the correlation between
measured variables. The level of statistical significance was set at a
two-tailed P value of ⱕ0.05. For t-tests evaluating differences between %Anaer and %Aer mean values of Dysf and N at different
supramaximal test durations, the smallest difference physiologically
worth detecting was considered to be 25%; accordingly, for such an
effect size and a two-tailed ␣ value ⫽ 0.05, a sample size of at least
15 subjects for each of the two study groups was required to yield a
statistical power of ⬎80%. The StatView 5.0.1. (SAS Institute, Cary,
NC) and Power And Precision 2 (Biostat, Englewood, NJ) software
packages were used for statistical calculations.
RESULTS
Demographic, clinical, and ergometric characteristics.
Study groups were well matched as to age, weight, body mass
index, and lean body mass values (Table 1). All Dysf patients
showed severely dysfunctioning and dilated left ventricles, and
all were on ␤-blockers and ACE inhibitors (Table 1).
At baseline CPX, Dysf had V̇O2 and power mean values
lower than N, both at VAT and peak effort; however, VAT V̇O2
expressed as a percentage of V̇O2peak did not differ between the
two groups (Table 2). V̇O2peak of Dysf expressed as a percentage of age- and sex-predicted maximum indicated a reduced
aerobic power, whereas that of N was very close to 100% of
Table 1. Demographic and clinical characteristics
n
Age, yr
Weight, kg
BMI, kg/m2
Lean body mass, kg
NYHA class
LVEF, %
LVEDV, ml/m2
␤-blockers, n (%)
ACE-inhibitors, n (%)
BNP, pg/ml
Dysf
N
19
66⫾5
77⫾9
26.5⫾2
60⫾7
2.1⫾0.5
27⫾10
126⫾50
19 (100)
19 (100)
175⫾75
17
61⫾6
79⫾10
28.3⫾3
62⫾5
Values are means ⫾ SD, number, or percentage. Dysf, patients with left
ventricular dysfunction; N, normal subjects; BMI, body mass index; NYHA,
New York Heart Association; LVEF, left ventricular ejection fraction;
LVEDV, left ventricular end-diastolic volume; ACE, angiotensin-converting
enzyme; BNP, brain natriuretic peptide.
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Anthropometric evaluation. Three skinfold thicknesses were measured in all subjects according to standard procedures (8) by means of
a Lafayette caliper. The skinfold sites used were chest, abdomen, and
thigh. Body density was calculated using the Jackson-Pollock prediction equations for white male adults (24), and percent body fat was
determined by the Siri formula (24).
Ergometric evaluation. All subjects underwent 1) a baseline ramp
CPX for V̇O2peak and VAT assessment; 2) three moderate-intensity
constant-power exercise tests for determination of the V̇O2/power
relationship; 3) three supramaximal constant-power exercise tests for
MAOD measurement. The terms “moderate-intensity” and “supramaximal” are to be intended as lower than VAT power and higher
than peak power reached at CPX, respectively. All tests were performed on a bicycle ergometer (Ergo-metrics 800S; Sensormedics,
Yorba Linda, CA).
Ramp CPX. After a 2-min unloaded cycling warm-up period, a
ramp protocol of 10 or 15 W/min (Dysf) and 15 or 20 W/min (N) was
started, and participants were encouraged to exercise until exhaustion.
Respiratory gas exchange measurements were obtained breath by
breath using a computerized metabolic cart (Vmax29; Sensormedics).
V̇O2peak was the mean oxygen uptake (V̇O2) value observed during the
last 30 s of the exercise period. Predicted maximal V̇O2 was determined by using a sex-, age-, and protocol-specific formula outlined by
Wasserman (32), and VAT was estimated by the V-slope and/or
respiratory equivalents methods (32).
Moderate-intensity constant-power exercise tests. Over 1 wk after
baseline CPX, all subjects performed three moderate-intensity constant-power exercise tests with respiratory gas exchange measurement at powers equal to 30%, 60%, and 90% of the VAT power.
Tests were performed in a random sequence on separate days.
After a 3-min resting baseline period, subjects started pedalling at
the established power, which was maintained for 10 min at a
pedalling rate of 60 revolutions/min (rpm).
Supramaximal constant-power exercise tests. During the 2 wk
following performance of moderate-intensity tests, all subjects underwent three supramaximal constant-power exercise tests with respiratory gas exchange measurement, in which the power was adjusted to
cause exhaustion in ⬃1–2 min, 2–3 min, and 3– 4 min on the basis of
previous data from our laboratory (19). After a 4-min warm-up at an
intensity of 30% peak power at baseline CPX and a 2-min rest period,
subjects attained a pedaling rate of 60 rpm within 20 s, and then the
established power was applied. Verbal motivation was provided by
the experimenters, and the test ended when patients or subjects were
unable to maintain 50 rpm. Tests were performed in random order and
separated by a rest period of at least 48 h.
Data analysis. Slope and intercept of the V̇O2/power relationship
were determined for each subject by calculating the regression of the
measured steady-state V̇O2 on the corresponding moderate-intensity
powers. The individual V̇O2/power relationship was then extrapolated
to the applied power for each of the three supramaximal tests, and
the corresponding estimated V̇O2 (estV̇O2) was determined. Assuming oxygen demand to be constant during the exercise period,
MAOD was then calculated as the difference between the accumulated oxygen demand and the measured accumulated oxygen
uptake as follows (20):
EFFORT ENERGY RELEASE IN LEFT VENTRICULAR DYSFUNCTION
Table 2. Ergometric characteristics
Peak power, W
Peak V̇O2 ml/min
Peak V̇O2, ml 䡠 kg⫺1 䡠 min⫺1
%Predicted V̇O2max
Peak V̇CO2, ml 䡠 kg⫺1 䡠 min⫺1
Peak RER
Peak V̇E, l/min
Peak HR, beats/min
Peak SBP, mmHg
VAT power, W
VAT V̇O2, ml 䡠 kg⫺1 䡠 min⫺1
VAT V̇O2%
Dysf
N
108⫾13*
1,302⫾154*
17.1⫾2.2*
62⫾9*
1,490⫾192*
1.14⫾0.03
56⫾16*
127⫾15†
155⫾24†
55⫾15*
10.2⫾1.5†
59⫾8
181⫾19
2,444⫾155
28.5⫾4
102⫾14
2,850⫾183
1.17⫾0.04
85⫾13
161⫾20
203⫾23
82⫾17
15.9⫾4
56⫾5
Values are means ⫾ SD. V̇O2, oxygen uptake; V̇O2max, maximal V̇O2;
V̇CO2, CO2 uptake; RER, respiratory exchange ratio; V̇E, ventilation; HR,
heart rate; SBP, systolic blood pressure; VAT, ventilatory anaerobic
threshold; VAT V̇O2%, V̇O2 at VAT as percentage of peak V̇O2. *P ⬍ 0.005
vs. N. †P ⬍ 0.001 vs. N.
tion of supramaximal tests in the two groups, whereas accumulated oxygen demand did increase significantly (Table 3).
Accordingly, %Anaer and %Aer decreased and increased,
respectively, with increasing test duration (Fig. 1). Of note,
accumulated oxygen demand was linearly related to test duration in both Dysf and N (r ⫽ 0.72 and 0.91, respectively; both
P ⬍ 0.001); as a consequence, %Anaer and %Aer did not differ
between Dysf and N for each test duration considered (45 ⫾
8% vs. 45 ⫾ 9% at 1–2 min test, 35 ⫾ 10% vs. 32 ⫾ 11% at
2–3 min test, and 23 ⫾ 9% vs. 25 ⫾ 11% at 3– 4 min test for
%Anaer; Fig. 1). The same was true also for %Anaer and %Aer
mean values in symptomatic and asymptomatic Dysf patients
(44 ⫾ 3% vs. 47 ⫾ 5% at 1–2 min test, 32 ⫾ 8% vs. 38 ⫾ 10%
at 2–3 min test, and 23 ⫾ 7% vs. 26 ⫾ 9% at 3– 4 min test for
%Anaer).
Since MAOD values did not differ with increasing supramaximal test duration in both groups, the mean MAOD value
of the three tests (meanMAOD) was calculated for each participant in the study. MeanMAOD correlated significantly with
V̇O2peak (Fig. 2), VAT V̇O2, and percent of predicted maximal
V̇O2 values in the total study population (r values between 0.74
and 0.77; all P ⬍ 0.0001). Moreover, no relationship was
found between both meanMAOD and V̇O2peak values and those
of blood natriuretic peptide levels in the Dysf group (r ⫽ 0.24
and 0.41, respectively; both P ⬎ 0.20).
DISCUSSION
The main finding of this study is that relative anaerobic vs.
aerobic contribution to total energy release during comparable
relative supramaximal effort is similar in patients with symptomatic and asymptomatic left ventricular dysfunction and
Table 3. Supramaximal constant-power test parameters
1–2 min
Power, W
%Peak power
Duration, s
accO2dem, ml/kg
MAOD, ml/kg
2–3 min
Power, W
%Peak power
Duration, s
accO2dem, ml/kg
MAOD, ml/kg
3–4 min
Power, W
%Peak power
Duration, s
accO2dem, ml/kg
MAOD, ml/kg
DYSF
N
155⫾25*†
143⫾23†
92⫾14†
37.3⫾8*†
16.7⫾4*
266⫾28†
147⫾15†
95⫾16†
58⫾14†
25.9⫾8
133⫾18*‡
123⫾16‡
142⫾22‡
55.9⫾12*§
20.1⫾7*
228⫾27‡
125⫾14‡
136⫾17‡
84.3⫾22‡
28.3⫾10
121⫾10*
112⫾9
212⫾35
75.3⫾10*
19.1⫾5*
195⫾11
108⫾10
221⫾44
98.6⫾20
28.2⫾12
Values are means ⫾ SD. %Peak power, percentage of basal cardiopulmonary exercise test peak power; accO2dem, accumulated oxygen demand;
MAOD, maximal accumulated oxygen deficit. *P ⬍ 0.05 vs. N. †P ⬍ 0.05 vs.
other tests. ‡P ⬍ 0.05 vs. 3– 4 min.
J Appl Physiol • VOL
Fig. 1. Relative anaerobic and aerobic contribution to total energy release
during supramaximal tests. 100% of total energy release is accumulated
oxygen demand and anaerobic energy release is maximal accumulated oxygen
deficit relative to accumulated oxygen demand. Dysf, patients with left ventricular dysfunction; N, normal subjects; NS, not statistically significant for
both aerobic and anaerobic energy release. *P ⬍ 0.05 vs. 2–3 min and 3– 4
min. †P ⬍ 0.05 vs. 3– 4 min.
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predicted (Table 2). Ventilation, heart rate, and systolic blood
pressure mean values at peak effort were significantly lower in
Dysf than in N, whereas peak respiratory exchange ratio did
not differ between the two groups (Table 2).
Relative anaerobic and aerobic contribution to total energy
release during supramaximal effort. Mean peak power was
significantly lower in Dysf than N for each supramaximal test
duration, and corresponded to 145 ⫾ 20%, 124 ⫾ 15%, and
110 ⫾ 10% of peak power at baseline CPX for 1–2 min, 2–3
min, and 3– 4 min supramaximal tests, respectively (Table 3).
Mean durations of 1–2 min, 2–3 min, and 3– 4 min supramaximal tests in the total study population were 93 ⫾ 15, 139 ⫾ 19,
and 216 ⫾ 40 s, respectively, with no differences between Dysf
and N.
MAOD, i.e., anaerobic contribution to total energy release,
and accumulated oxygen demand mean values were significantly lower in Dysf than N for each supramaximal test
duration; however, MAOD did not vary with increasing dura-
99
100
EFFORT ENERGY RELEASE IN LEFT VENTRICULAR DYSFUNCTION
normal subjects, even when working at markedly different
absolute powers. These results indicate that energetic metabolism during supramaximal exercise is independent of individual exercise tolerance and that relative anaerobic vs. aerobic
contribution in this effort domain remains the same within the
physiology- or pathology-induced limits to peak exercise performance, irrespective of effort absolute intensity.
Relative anaerobic and aerobic contribution to total energy
release. The contribution of anaerobic metabolism to exercise
energetic needs has been evaluated in patients with left ventricular dysfunction in the effort moderate- and high-/very
high-intensity domains (10, 20, 25, 27). Available data indicate
that patients with left ventricular dysfunction have a higher
anaerobic energetic yield (as expressed by slower V̇O2 onkinetics and/or larger oxygen deficit) than normal subjects
when matched absolute workloads are considered (10, 20, 25,
27). This is expected when considering that, in this case,
patients are working at a higher percentage of their V̇O2peak
(and possibly at a lower delta V̇O2/delta power) than normal
subjects. On the contrary, when matched relative, rather than
absolute, exercise intensities are considered (10, 20, 27) or
when V̇O2 on-kinetics descriptors are normalized for V̇O2peak
values (25), a similar anaerobic contribution in patients and
normal subjects is evident. However, in the moderate-intensity
domain, determination of the relative anaerobic contribution to
total energy release is strictly protocol dependent, since, by
definition, no fatigue is expected to occur and exercise duration
is set by operators, i.e., the longer the exercise duration the
lower the relative anaerobic energetic release, whereas in
the high/very high domain the appearance of the V̇O2 slow
component makes a precise definition of oxygen deficit
impossible (34). Conversely, during supramaximal effort,
the relative anaerobic contribution to total energy yield is
unequivocally measurable since exercise duration (and thus
accumulated energy demand) has a finite value, and MAOD
evaluation allows a reasonable estimate of anaerobic energetic release (17).
This study evaluated for the first time such parameters
during supramaximal effort in patients with left ventricular
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Fig. 2. Relationship between the mean of maximal accumulated oxygen deficit
values (meanMAOD) of the three supramaximal tests and peak oxygen uptake
(V̇O2peak) values in the total study population.
dysfunction, revealing that the relative anaerobic vs. aerobic
contribution to total energetic yield is similar to that of normal
subjects at comparable relative effort intensities, notwithstanding significantly different absolute workloads. Such a finding is
matched to that of similar times to exhaustion at comparable
effort relative intensities in the two groups, which strengthens
still further the concept of a similar anaerobic vs. aerobic
energetic contribution in Dysf and N. Moreover, %Anaer and
%Aer values were strikingly close to those reported in normal
subjects for similar test durations, obtained by fitting data from
over 30 studies using various methods for anaerobic vs. aerobic
contribution determination (7). Interestingly, the same results
were obtained when symptomatic and asymptomatic Dysf
patients were compared; this is of note, considering that
asymptomatic Dysf patients have usually been found to have a
physiological and metabolic response to effort very close to
that of normal subjects (9).
Pathophysiological correlates. A tendency toward a higher
reliance than normal subjects on anaerobic energetic metabolism during effort is classically described in patients with left
ventricular dysfunction, as witnessed by a more rapid depletion
of PCr stores and the development of higher intracellular
acidosis (14, 16, 37), a reduced aerobic enzyme activity together with reduced mitochondrial volume (5, 21, 29), and the
shift to a higher percentage of type II fibers and myosin heavy
chains (26, 31) with respect to normal subjects. Our whole
body metabolic data do not fit with this picture, showing a
normal-like relative anaerobic vs. aerobic energetic yield in
both symptomatic and asymptomatic patients with left ventricular dysfunction during supramaximal effort. This apparent
contradiction may be due to several reasons. Indeed, authors
who used magnetic resonance spectroscopy for metabolic analyses evaluated patients and controls at matched absolute workloads, thus with patients working at a higher percentage of their
peak exercise capacity. On the other hand, histological studies
may suffer from limitations such as high interindividual muscle
fiber-type proportion and enzyme activity composition variability (28), large overlap in enzyme activity levels between
fast and slow skeletal muscle fibers (23), and existence of
hybrid fibers, i.e., containing three or more myosin heavy chain
isoforms (23), which may complicate inferences from bioptic
studies dealing with energetic metabolism. In addition, several
lines of evidence suggest the possibility of a maintained relative aerobic energetic yield in patients with left ventricular
dysfunction. First, phase II of V̇O2 on-kinetics, which reflects
skeletal muscle oxidative metabolic control (34), has been
found to be similar in chronic heart failure patients and normal
subjects at matched relative effort intensities (10). Second,
ACE inhibitors can prevent mitochondrial dysfunction in rats
with myocardial infarction-induced left ventricular dysfunction
(38) and reverse pathology-induced myosin heavy chain modifications in chronic heart failure patients (30). Third, oxidative
capacity of skeletal muscle mitochondria, as evaluated in
saponin-skinned myofibers (6, 18) or as mitochondrial ATP
production rates (36), has been found to be similar in patients
with chronic heart failure and sedentary normal subjects.
Fourth, and most important, skeletal muscle fibers contractile
and metabolic phenotypes may not be matched either in animals (1) or chronic heart failure patients (18), showing the
possibility of a preserved mitochondrial oxidative capacity in
the presence of an increased glycolitic activity and a slow to
EFFORT ENERGY RELEASE IN LEFT VENTRICULAR DYSFUNCTION
ACKNOWLEDGMENTS
The authors are grateful to Elena Bonanomi and Alfio Agazzone for
technical support and to Rosemary Allpress for careful revision of the English
manuscript.
J Appl Physiol • VOL
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fast phenotype transition. Finally, MAOD and V̇O2peak have
been proposed to be strictly related (34), as confirmed in vivo
both in normal subjects and patients with left ventricular
dysfunction in this and a previous study from our laboratory
(20), underlining that anaerobic and aerobic metabolisms cannot be considered as separate entities but as closely linked and
coordinated energetic systems (3).
As a whole, these findings provide a rational basis to the
preserved proportionality between anaerobic and aerobic energetic contribution during supramaximal effort observed in our
patients, at least at the disease stages evaluated in this study.
Such a constancy of the relative anaerobic/aerobic energy
release, observed in this and other papers over the whole range
of effort intensity domains, can be seen as a basal and inherent
characteristic of human metabolism during transitions from
lower to higher energy demand levels, revealing a similar
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within the physiology- or pathology-induced limits to individual exercise tolerance. Moreover, the finding of a preserved
anaerobic/aerobic energy release ratio in Dysf patients argues
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to the disease pathophysiological picture (12). Finally, the
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remains to be determined, even if the absence of a significant
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energetic metabolism during effort, at least at the disease
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The extrapolation of the below-anaerobic threshold V̇O2/W
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V̇O2/W relationship, projecting the V̇O2 steady-state value
(when attainable) at values higher than expected according to
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lends support to the methodology we used for MAOD determination.
In conclusion, this study demonstrates the existence of a
similar relative anaerobic vs. aerobic metabolism contribution
to total energy release during supramaximal effort in patients
with symptomatic and asymptomatic left ventricular dysfunction and normal subjects. Such a behavior seems to describe
an inherent characteristic of the anaerobic/aerobic interaction
during effort in humans within the physiology- or pathologyinduced limits to individual exercise tolerance. Further data are
needed to confirm the whole body energetic picture described
in this study, which could be substantiated by taking into
consideration patients with pathologies other than left ventricular dysfunction in which a reduced exercise tolerance is part
of the clinical picture.
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