Skeletal Muscle Adaptations to Interval Training in Patients With ...

Skeletal Muscle Adaptations to Interval
Training in Patients With Advanced
COPD*
Ioannis Vogiatzis, PhD; Gerasimos Terzis, PhD; Serafeim Nanas, MD;
Grigoris Stratakos, MD; Davina C. M. Simoes, PhD; Olga Georgiadou, MSc;
Spyros Zakynthinos, MD; and Charis Roussos, MD, PhD
Study objectives: To investigate the response to interval exercise (IE) training by looking at
changes in morphologic and biochemical characteristics of the vastus lateralis muscle, and to
compare these changes to those incurred after constant-load exercise (CLE) training.
Design: Randomized, controlled, parallel, two-group study (IE vs CLE training).
Setting: Multidisciplinary, outpatient, hospital-based, pulmonary rehabilitation program.
Patients: Nineteen patients with stable advanced COPD (mean SEM FEV 1, 40 4% predicted).
Interventions: Patients (n 10) assigned to IE training exercised at a mean intensity of
124 15% of baseline peak exercise capacity (peak work rate [Wpeak]) with 30-s work periods
interspersed with 30-s rest periods for 45 min/d. Patients (n 9) allocated to CLE training
exercised at a mean intensity of 75 5% Wpeak for 30 min/d. Patients exercised 3 d/wk for 10
weeks.
Measurements and results: Needle biopsies of the right vastus lateralis muscle were performed
before and after rehabilitation. After IE training, the cross-sectional areas of type I and IIa fibers
were significantly increased (type I before, 3,972 455 m 2 ; after, 4,934 467 m 2 [p 0.004];
type IIa before, 3,695 372 m 2 ; after, 4,486 346 m 2 [p 0.008]), whereas the capillary-tofiber
ratio was significantly enlarged (from 1.13 0.08 to 1.24 0.07 [p 0.013]). Citrate
synthase activity increased (from 14.3 1.4 to 20.5 4.2 mol/min/g), albeit not significantly
(p 0.097). There was also a significant improvement in Wpeak (by 19 5%; p 0.04) and in
lactate threshold (by 17 5%; p 0.02). The magnitude of changes in all the above variables was
not significantly different compared to that incurred after CLE training. During training
sessions, however, ratings of dyspnea and leg discomfort, expressed as fraction of values achieved
at baseline Wpeak, were significantly lower (p < 0.05) for IE training (73 9% and 60 8%,
respectively) compared to CLE training (83 10% and 87 13%, respectively).
Conclusions: High-intensity IE training is equally effective to moderately intense CLE training in
inducing peripheral muscle adaptations; however, IE is associated with fewer training symptoms.
(CHEST 2005; 128:3838–3845)
Key words: interval exercise; obstructive lung disease; pulmonary rehabilitation; skeletal muscle biopsy
Abbreviations: CLE constant-load exercise; CS citrate synthase; CSA cross sectional area; Dlco diffusion
capacity of the lung for carbon monoxide; IC inspiratory capacity; IE interval exercise; LT lactate threshold;
PFK phosphofructokinase; V˙ o 2 oxygen uptake; Wpeak peak work rate
Skeletal muscle dysfunction is common in patients
with advanced COPD, and it contributes importantly
to limiting functional capacity and quality of
life. 1–3 Morphologic and biochemical changes within
the vastus lateralis muscle of these patients include
abnormal fiber-type proportions, reduced fiber
cross-sectional area (CSA), and decreased muscle
capillarity and oxidative enzyme activities. 3–8 These
changes have been associated with an early activation
of anaerobic glycolysis, lactic acidosis, and premature
establishment of muscle fatigue during exercise. 5,9
Endurance training reverses, at least in part, these
abnormalities by inducing significant improvements
in fiber CSA and oxidative enzyme activities, thereby
enhancing exercise tolerance. 10–12
Although high-intensity constant-load exercise
(CLE) is generally argued to be needed for an
improvement in exercise capacity, 13 ventilatory-limited
patients are usually unable to sustain such
intensities for sufficiently long periods. 14 Since trainability
in patients with severe COPD is limited,
various attempts to improve the outcome of training,
3838 Clinical Investigations
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such as oxygen supplementation or continuous positive
airway pressure, have been employed. 13 An
alternative approach that allows high-intensity exercise
to be performed for sufficiently long periods of
time is interval exercise (IE). In healthy subjects with
this type of exercise, it is possible to impose maximal
loads on both muscles and oxygen-transporting organs
without significant engagement of anaerobic
processes, thus allowing a great amount of work to be
performed before exhaustion sets in. 15 In patients
with advanced COPD, IE training, consisting of
repeated bouts of high or even maximal-intensity
work separated by periods of lower intensity work or
rest, has been shown to be associated with a small
increase in lactate concentration, stable ventilation,
and low symptoms of dyspnea and leg discomfort,
thus allowing the total amount of work performed to
be significantly greater than at CLE training. 16–17
In addition, application of IE training into pulmonary
rehabilitation has been shown to be an equally
effective alternative to moderately intense CLE
training in terms of improving exercise tolerance and
quality of life. 18 As there is evidence 19–20 that patients
with advanced COPD have a significant metabolic
reserve capacity that is only evident when
muscle activity is somewhat freed from ventilatory
constraints, it was hypothesized that application of
high-intensity IE training in the rehabilitation of
these patients would induce significant peripheral
muscle adaptations leading to improvements in exercise
tolerance. Consequently, the purpose of the
present study was primarily to investigate the response
to high-intensity IE training by specifically
looking at changes in morphologic and biochemical
characteristics of the vastus lateralis muscle. In
addition, we compared the magnitude of peripheral
muscle adaptations induced by high-intensity IE
training to that incurred after implementation of the
commonly applied moderately intense CLE training
modality.
*From the Department of Critical Care Medicine and Pulmonary
Services (Drs. Nanas, Stratakos, Simoes, Zakynthinos, and Roussos),
Pulmonary Rehabilitation Centre, Evangelismos Hospital,
and Thorax Foundation “M. Simou and G.P. Livanos Laboratories”;
Department of Physical Education and Sport Science (Drs.
Terzis and Vogiatzis, and Ms. Georgiadou), National & Kapodistrian
University of Athens, Athens, Greece.
This work was supported in part by the European Community
CARED FP5 project (No. QLG5-CT-2002–0893) and by the
Thorax Foundation.
Manuscript received March 4, 2005; revision accepted September
26, 2005.
Reproduction of this article is prohibited without written permission
from the American College of Chest Physicians (www.chestjournal.
org/misc/reprints.shtml).
Correspondence to: Ioannis Vogiatzis, PhD, National & Kapodistrian
University of Athens, Medical School, Thorax Foundation 3
Ploutarhou Str. 106 75, Athens, Greece; e-mail:gianvog@phed.
uoa.gr
Subjects
Materials and Methods
Patients included 16 men and 3 women with stable, advanced
COPD who satisfied the following criteria: (1) postbronchodilator
FEV 1 50% of predicted and FEV 1/FVC 70% without
significant reversibility ( 12% change of the initial FEV 1 value),
(2) optimized medical therapy, and (3) no clinical evidence of
exercise-limiting cardiovascular or neuromuscular diseases. Patients
signed an informed consent form that was approved by the
University Ethics Committee.
Study Design
The study was designed as a randomized, controlled, parallel,
two-group study. Once it was verified that patients met the
selection criteria, they were randomly assigned to one of the two
training modalities: IE or CLE. Stratified randomization was
used to achieve approximate balance of certain characteristics
(Table 1), including FEV 1 ( 40 or 40% of predicted) and
peak work rate (Wpeak) [ 50 or 50 W] that was assessed by
a ramp-incremental cycle ergometer test.
Pulmonary Function Assessment
Spirometry and diffusion capacity of the lung for carbon
monoxide (Dlco) were performed (Masterlab; Jaeger; Wurzburg,
Germany) according to recommended techniques. 21 Arterial
blood gas was also analyzed at rest (ABL330; Radiometer;
Copenhagen, Denmark).
Rehabilitation Program
The rehabilitation program was multidisciplinary and included
supervised exercise training, breathing control and relaxation
techniques, methods of clearance of pulmonary secretions, disease
education, dietary advice, and psychological support on
issues relating to chronic disability. Similarly to our previous
rehabilitation study, 18 the exercise prescription was designed to
present patients with a similar overall training load. Patients
assigned to the IE group were instructed to exercise on electromagnetically
braked cycle ergometers (Cateye Ergociser,
ECl600; Cat Eye; Osaka, Japan) at an intensity initially targeted
Table 1—Baseline Lung Function Characteristics
Between the IE and the CLE Training Groups*
Characteristics IE (n 10) CLE (n 9)
Age, yr 64 3 67 2
Body mass index,
25.9 1.2 26.9 1.3
kg/m 2
FEV1, L (% predicted) 1.12 0.15 (44 6) 1.07 0.16 (39 6)
FVC, L (% predicted) 2.64 0.28 (82 8) 2.67 0.27 (75 7)
FEV1/FVC, % 42 4 44 6
Dlco, % predicted 51 9 47 8
IC, % predicted 71 6 71 12
Pao2,mmHg 69 6 64 4
Paco2,mmHg 39 1 41 1
pH 7.43 0.01 7.44 0.01
Arterial oxygen
saturation, %
94 1 92 1
*Data are presented as mean SEM.
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to 100% of Wpeak, assessed prior to rehabilitation by a rampincremental
cycle ergometer test (see below), with 30 s of work
interspersed with 30-s rest periods for 45 min/d, 3 days per week,
for 10 weeks. Patients assigned to the CLE group were instructed
to exercise for the same weekly frequency and total duration as
the IE group but at an intensity that was initially equivalent to
60% of baseline Wpeak for 30 min each time. Therefore, at the
outset of the study, the total amount of work done per session by
each member of the IE group was designed to equate the work
that these patients would have done had they been assigned to
the CLE group. As training principles require the training
intensity to parallel the improvement in physical fitness, 13 the
weekly training load for the IE group was designed to represent
100% during weeks 1 to 3, 120% during weeks 4 to 6, and 140%
of Wpeak during the last 4 weeks. For the CLE group, the load
was designed to represent 60%, 70%, and 80% of Wpeak,
respectively, for the three weekly periods. Supervision during
training involved measurements of pulse oxygen saturation, heart
rate, and sensation of dyspnea and leg discomfort. During
training, supplemental oxygen was provided at a rate of 1.5 to 2.0
L/min in six patients in the IE group and four patients in the CLE
group.
Muscle Biopsy
Within a week before and after the rehabilitation program,
percutaneous biopsies of the right vastus lateralis muscle were
performed at mid-thigh (15 cm above the patella) as described by
Bengstrom. 22 Briefly after local anesthesia with 1.5 mL of
lidocaine 2%, a 1-cm skin incision was performed and muscle
samples were obtained. Samples were placed in embedding
compound and immediately frozen in isopentane precooled to its
freezing point. All samples were kept at 80°C until the day of
analysis. The pretraining and posttraining muscle biopsy samples
were obtained 10-cm apart from each other.
Skeletal Muscle Analysis
Fiber Typing, CSA, and Capillarization: All muscle specimens
were coded and analyzed without knowledge of the clinical data.
Samples obtained before and after the training period were
analyzed in pairs at the same time. Cryostat transverse sections of
10 m in thickness were cut at 20°C and were stained for
myofibrillar adenosine triphosphatase after preincubation at pH
values of 4.3, 4.6, and 10.3. 23–24 A mean of 331 14 muscle
fibers were analyzed from each slice and classified as type I, IIa,
or IIb. The CSA of a minimum of 200 fibers was measured in
each slice with an image analysis system (ImagePro; Media
Cybernetics; Silver Spring, MD) at a known and calibrated
magnification. A-amylase-periodic acid shift was used to visualize
capillaries. The number of capillaries identified in a certain area
was divided by the number of fibers found in the corresponding
muscle section. 25
Enzyme Activity: The activities of phosphofructokinase (PFK)
[enzyme code 2.7.1.11] and citrate synthase (CS) [enzyme code
4.1.3.7] were studied using described spectrophotometric techniques.
26
Assessment of Exercise Capacity
Before and after the training program, an incremental protocol
was performed on an electromagnetically braked cycle ergometer
(Ergoline 800; SensorMedics; Yorba Linda, CA). After 3-min of
baseline measurements, followed by 3-min of unloaded pedaling,
the work rate was increased every min by 5 or 10 W to the limit
of tolerance while patients maintained a pedaling frequency of 60
revolutions/min. Gas exchange and ventilatory variables were
recorded breath-by-breath (V˙ max 229; SensorMedics). At baseline,
during unloaded cycling and incremental exercise, patients
performed inspiratory capacity (IC) maneuvers at 3-min intervals
according to previously described methods. 27 The V-slope technique
was used to detect the oxygen uptake (V˙ o 2) at which the
lactate threshold (LT) occurred. 28 The modified Borg Scale 29 was
used to rate the magnitude of dyspnea and leg discomfort.
Statistical Analysis
Data are presented as mean SEM. The within-group and
between-group differences were analyzed using repeated-measures
analysis of variance. Between-group comparisons of baseline
characteristics were carried out by unpaired t test. The level
of significance was set at p 0.05.
Results
Patient Characteristics
As shown in Table 1, patients in both groups were
characterized by severe airflow limitation, moderate
hypoxemia without carbon dioxide retention at rest,
and reduced values for Dlco and IC. At the outset
of the study pulmonary function, exercise capacity
and morphologic characteristics of the vastus lateralis
muscle were not significantly different between
the two groups, whereas exercise capacity was severely
compromised in both groups (Tables 1–3).
Training Program
The average training intensity sustained at 100%
and 60% of baseline Wpeak during IE and CLE
training was achieved at the fifth and fourth sessions,
respectively. The mean intensity sustained during
training increased progressively in the IE group
and corresponded to 105 13%, 130 13%, and
138 16% of baseline Wpeak and to 66 3%,
Table 2—Vastus Lateralis Muscle Characteristics of
Patients Assigned to the IE and CLE Training Groups
at the Outset of the Study*
Characteristics IE (n 10) CLE (n 9)
Fiber-type distribution, %
Type I 36 5 40 5
Type IIa 50 6 46 6
Type IIb
CSA, m
13 2 13 3
2
Type I 3,972 455 4,634 262
Type IIa 3,695 372 3,795 231
Type IIb 3,027 407 3,127 218
Capillary-to-fiber ratio 1.13 0.08 1.30 0.09
Capillary density, capillaries/mm 2
266 18 268 12
CS activity, mol/min/g 14.3 1.4 21.6 2.6†
PFK activity, mol/min/g 61.3 22.2 63.8 11.7
*Data are presented as mean SEM.
†p 0.05
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Table 3—Responses to the Incremental Exercise Test
Between the IE and the CLE Training Groups*
Characteristics IE (n 10) CLE (n 9)
Wpeak, W 53 9 61 8
Peak V˙ o2, L/min
Peak V˙ co2, L/min
0.87 0.09
0.89 0.11
0.97 0.10
0.96 0.10
LT, L/min 0.64 0.05 0.68 0.03
Peak V˙ e, L/min 37.9 4.2 37.2 3.3
Peak V˙ e/MVV, % 88 7 86 6
Peak respiratory rate, breaths/min 33 3 34 2
Peak VT, L 1.19 0.13 1.12 0.05
Change in IC, L 0.49 0.09 0.63 0.07
Peak heart rate, beats/min 132 6 122 10
Peak pulse oxygen saturation, % 93 1 93 1
Peak dyspnea, Borg 4.1 0.5 4.1 0.6
Peak leg fatigue, Borg 4.8 0.7 4.0 0.6
*Data are presented as mean SEM. V˙ co2 carbon dioxide output;
V˙ e minute ventilation; MVV maximum voluntary ventilation;
VT tidal volume.
75 5%, and 85 5% of baseline Wpeak in the
CLE group at weeks 3, 6 and 9, respectively. Examination
of the mean training intensities revealed that
the total amount of work performed by the two
groups during training was not significantly different.
However, during the training sessions ratings of
dyspnea and leg discomfort, expressed as fraction of
the peak values achieved at baseline Wpeak, were
significantly (p 0.05) lower for IE training
(73 9% and 60 8%, respectively) compared to
CLE training (83 10% and 87 13%, respectively)
[Fig 1].
Skeletal Muscle Adaptations
Fiber Typing and CSA Determination: The proportion
of type I and type IIa fibers changed very little
after both training modalities (IE by 3% and 2%,
respectively; CLE by 2% and 1%, respectively). However,
the proportion of type IIb fibers was significantly
reduced in both groups (IE: from 13 2to7 1%
[p 0.001]; CLE: from 13 3to9 2% [p 0.02]).
After rehabilitation, the CSA of type I and type IIa
fibers was increased in both groups (IE: type I before,
3,972 455 m 2 ; after, 4,934 468 m 2 [p 0.004];
type IIa before, 3,695 372 m 2 ; after, 4,486 346
m 2 [p 0.008]); (CLE: type I before, 4,634 262
m 2 ; after, 5,119 273 m 2 [p 0.012]; type IIa
before, 3,795 231 m 2 ; after, 4,183 180 m 2
[p 0.021]) [Fig 2, 3]. The CSA of type IIb fibers
increased significantly (p 0.001) only after CLE
training (from 3,127 218 to 3,520 204 m 2 ). The
magnitude of change in fiber type and CSA was not
significantly different between groups.
Muscle Capillarization: The capillary-to-fiber ratio
was significantly enlarged after training (IE, from
Figure 1. Average values for training intensity sustained during the program sessions (top left, A),
cardiac frequency (fc) [bottom left, B], dyspnea (top right, C), and leg discomfort (bottom right, D) for
the IE (open circles) and CLE (closed circles) training groups. All parameters are expressed as fractions
of the peak values achieved at Wpeak during the baseline incremental test. Data are shown as
mean SEM.
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Figure 2. Fiber-type distribution (percentage) of the vastus
lateralis muscle before (open squares) and after (gray squares)
training for the IE group (top, A) and the CLE group (bottom, B).
*p 0.05, comparisons between before (open squares) and after
training (gray squares). Data are presented as mean SEM.
1.13 0.08 to 1.24 0.07 [p 0.013]; CLE, from
1.30 0.09 to 1.45 0.09 [p 0.024]) [Fig 4]. The
magnitude of change in capillarization was not significantly
different between groups.
Enzyme Activity: The activity of PFK was significantly
reduced only after CLE (from 63.8 11.8
to 39.8 10.3 mol/min/g [p 0.01]; IE, from
61.3 22.2 to 56.1 19.9 mol/min/g), whereas CS
activity increased, albeit not significantly (IE, from
14.3 1.4 to 20.5 4.2 mol/min/g [p 0.097];
CLE, from 21.6 2.6 to 30.2 7.7 [p 0.23]
mol/min/g). The magnitude of change in enzyme
activities was not significantly different between
groups.
Exercise Capacity
After rehabilitation, there were significant improvements
for both groups in Wpeak (IE, from
53 9to6310W[p0.04]; CLE, from 61 8
to 70 9 W [p0.001]) and in LT (IE, from
0.64 0.05 to 0.75 0.07 L/min [p 0.01]; CLE,
from 0.68 0.03 to 0.80 0.06 L/min [p 0.03]),
whereas there was a tendency of improvement in
Figure 3. Changes in the CSA of the different fiber types of the
vastus lateralis muscle following IE training (top, A) and CLE
training (bottom, B). *p 0.05, comparisons between before
(open squares) and after training (gray squares). Data are presented
as mean SEM.
peak V˙ o 2 in both groups (IE by 9%; CLE by 5%). At
an identical work rate during the incremental test,
there was a significant reduction in minute ventilation
(by 16%; from 37.9 4.2 to 31.8 2.9 L/min;
[p 0.009]) only in the IE group, whereas the reduction
in IC changes from rest (from 0.49 0.09 to
0.35 0.13 L) was not significant (p 0.16).
Furthermore, at an identical work rate, there were
also significant reductions in perception of dyspnea
(from 4.1 0.5 to 2.6 0.3 [p 0.04]) and leg
discomfort (from 4.8 0.7 to 2.8 0.3 [p 0.007])
only after IE training.
Discussion
The impetus to study the efficacy of IE training in
patients with advanced COPD derives from studies
16–18 demonstrating that IE allows the application
of intense loads on peripheral muscles without the
attainment of the reduced ventilatory ceiling. As
there is evidence 19–20 that patients with advanced
COPD have a significant metabolic reserve capacity
that is only evident when muscular work is not
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Figure 4. Changes in the capillary-to-fiber ratio (top, A), PFK
(center, B), and CS activity (bottom, C) of IE training and CLE
training. *p 0.05, comparisons between before (open squares)
and after training (gray squares). Data are presented as
mean SEM.
influenced by central ventilatory limitations, it was
hypothesized that implementation of IE would allow
significant peripheral muscle adaptations to take
place leading to physiologic training responses. The
present study reveals that in patients with advanced
COPD, IE training induces significant changes in
the structure and function of the vastus lateralis
muscle. These changes, although not significantly
different from those induced by the implementation
of moderately intense CLE, were achieved with
fewer training symptoms compared to CLE training.
At baseline, structural and functional abnormali-
ties within our patients’ vastus lateralis muscles
(Table 2) are consistent with earlier reports 4–5,20
comparing patients with advanced COPD with agematched
healthy subjects. These abnormalities, including
abnormal proportion of type I fibers, muscle
capillarity, and CS activity, were accompanied by a
reciprocal high frequency of type II fibers and PFK
activity. 4,30 Furthermore, the observed values for
CSA of both type I and IIa fibers are in line with
previously published reports, 4,8 demonstrating that
the CSA of these fiber types in COPD patients are
lower compared to those of age-matched healthy
subjects. 4–5,20 Such changes within the muscles explain,
at least in part, the substantially reduced
capacity for aerobic work during the baseline incremental
exercise test (Table 3). Besides these skeletal
muscle abnormalities, dynamic hyperinflation and its
detrimental consequences to perceived dyspnea also
contributed to exercise intolerance. 15
Application of rehabilitative IE training yielded
morphologic and physiologic changes within the
vastus lateralis muscle that increased its oxidative
capacity. This can be conveyed by the significantly
enhanced capillary-to-fiber ratio and the increased
activity of CS after training. These improvements in
oxidative capacity within the vastus lateralis muscles
are likely to be associated with the significant
changes that occurred in the LT after training.
Previous studies 10–12 have shown that the increase in
the LT following exercise training in COPD patients
is indicative of a smaller increase in blood lactic acid
concentration for a given level of exercise, which, in
part, reflects the improved capacity for oxidative
metabolism within the trained muscles. Additionally,
an important physiologic training effect that was
likely mediated by the shift in the LT is that, at a
given level of exercise during the incremental test
after IE training, ventilatory requirement was significantly
reduced. 9,14 This ventilatory adaptation is
likely to have contributed to the lower degree of
dynamic hyperinflation and perception of dyspnea.
Furthermore, an improvement in muscle oxidative
metabolism would justify the significantly reduced
degree of muscle fatigability that we observed at an
identical workload during the incremental test.
The magnitude of improvement in muscle capillarity,
CS activity, and LT following implementation
of IE is very similar to that induced by the moderately
intense CLE regime, which is in accordance
with other studies 4,10,12 employing CLE training in
patients with severe COPD. In fact, the majority of
changes that took place in the vastus lateralis muscles
following IE training are consistent with those described
in previous studies for CLE training. Accordingly,
after IE training the magnitude of enlargement
in the CSA of both type I and IIa fibers is
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similar to that observed by Whittom et al 4 after
implementation of CLE training in patients with
severe airway obstruction and did not differ from
that demonstrated in our CLE training group. In
addition, our findings on the effects of IE are in line
with the findings from studies 31–34 that employed
high-intensity IE training in healthy subjects, demonstrating
a significant increase in the CSA of both
type I and IIa fibers and in the activity of CS.
However, the present study is the first in patients
with COPD to demonstrate a significant improvement
in the capillary-to-fiber ratio after both exercise
training modalities. Furthermore, this is the first
study to demonstrate a significant alteration in the
fiber-type distribution within the vastus lateralis
muscle after training in patients with COPD. Accordingly,
there was a significant reduction in the
proportion of type IIb fibers following both training
regimes. These findings are in accordance with
studies 31–32,34 in healthy subjects demonstrating that
it is possible to induce shifts in the distribution of the
subgroups of the fast twitch fibers with training. The
similarity of changes in peripheral muscle characteristics
induced by the two different modalities extends
our previous findings 18 by demonstrating that in
COPD patients IE is equally effective to CLE in
inducing significant physiologic effects, providing
that the imposed training load remains comparable
between training regimes.
Although our patients in both groups exhibited
significant improvements in the structure and function
of their muscles, this did not directly translate
into significant improvements in peak V˙ o 2, possibly
because of the early attainment of their reduced
ventilatory ceiling at high work rates. 19 Therefore,
constant-load submaximal exercise and isolated dynamic
20 or isometric 8 knee-extensor exercise might
constitute more appropriate testing tools in order to
evaluate the improvement in muscle function irrespective
of the decrement in lung function.
Classical studies 35–36 on muscle fiber metabolism
utilizing the glycogen depletion technique have
shown that with IE glycogen depletion is similar
between type I and II fibers, hence suggesting that
both fiber types are recruited to a similar degree
during IE. These studies 36 have also shown that the
capacity to reload the myoglobin stores and partially
restore the phosphocreatine levels during the recovery
phases 31 allows a more oxidative degradation of
glycogen; this has been proposed as the principal
mechanism for the slowed glycolysis and the relatively
low accumulation of lactate during IE. Consequently,
IE appears to be a more suitable mode of
exercise for the severe COPD patient, as it relies on
the periodic recruitment of both fast and slow twitch
fibers. 35 As lactic acidosis puts particular stress on
the ventilatory system and is associated with the
premature onset of muscle fatigue, the small increase
in lactate typically observed during IE 16–17
appears to be beneficial to the COPD patient by
allowing lower sensation of dyspnea and leg discomfort
during training compared to CLE. Although IE
consists of a sequence of on-and-off high-intensity
muscular loads, its tolerability in the context of
perceived respiratory and peripheral muscle discomfort
has been proven to be better than that of CLE. 17
Nevertheless, older patients with COPD have to
initially familiarize themselves with the exercise and
rest intervals in order to follow the right sequence of
work and rest intervals for the required period.
When the exercise apparatus provides a display of
time and power output, patients have to initially
dedicate few sessions to get accustomed with the
training protocol.
In summary, we have shown that in patients with
advanced COPD, implementation of brief, highintensity
bouts of exercise, alternated with equally
brief periods of rest, yields significant adaptations in
the vastus lateralis muscles that are similar to those
obtained by CLE. However, IE training induces
lower training symptoms than CLE training, and
hence it may provide a good alternative strategy in
patients with severe COPD.
ACKNOWLEDGMENT: We thank Drs. E. Kosmas and E.
Kastanakis for their contribution to the study. We are grateful to
Professor P. Manta from the Department of Neurology,
Eginiteion Hospital, for providing the necessary facilities to
analyze the muscle specimens.
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