Download Skeletal muscle structure and function in response to electrical

ARTICLE IN PRESS
Respiratory Medicine (2007) 101, 1236–1243
Skeletal muscle structure and function in response
to electrical stimulation in moderately impaired
COPD patients$
Simone Dal Corsoa,1, Lara Nápolisa, Carla Malagutia, Ana Cristina Gimenesa,
André Albuquerquea, Cristiano Rabelo Nogueiraa, Marcelo Bicalho De Fuccioa,
Roberto D.B. Pereirab, Acari Bulleb, Niall McFarlanec, Luiz E. Nerya,
J. Alberto Nedera,
a
Pulmonary Function and Clinical Exercise Physiology Unit (SEFICE), Division of Respiratory Diseases,
Department of Medicine, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
b
Neuromuscular Division, Federal University of São Paulo (UNIFESP), São Paulo, São Paulo, Brazil
c
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, UK
Received 10 May 2006; accepted 25 October 2006
Available online 14 December 2006
KEYWORDS
Chronic obstructive
pulmonary disease;
Electrical stimulation;
Skeletal muscle;
Rehabilitation;
Strength
Summary
Study objective: To determine the structural and functional consequences of highfrequency neuromuscular electrical stimulation (hf-NMES) in a group of moderately
impaired outpatients with chronic obstructive pulmonary disease (COPD).
Design: A prospective, cross-over randomized trial.
Setting: An university-based, tertiary center.
Patients and materials: Seventeen patients (FEV1 ¼ 49.6713.4% predicted, Medical
Research Council dyspnoea grades II–III) underwent 6-weeks hf-NMES (50 Hz) and sham
stimulation of the quadriceps femoris in a randomized, cross-over design. Knee strength
was measured by isokinetic dynamometry (peak torque) and leg muscle mass (LMM) by
DEXA; in addition, median cross-sectional area (CSA) of type I and II fibres and
capillary–fibre ratio were evaluated in the vastus lateralis. The 6-min walking distance
(6MWD) was also determined.
Abbreviations: COPD, chronic obstructive pulmonary disease; CSA, cross-sectional area; DEXA, dual-energy X-ray absorptiometry; DLCO,
carbon monoxide diffusing capacity; FEV1, forced expiratory volume in 1 s; FFM, fat-free mass; FVC, forced vital capacity; LMM, leg muscle
mass; MHC, mysosin heavy chain; 6MWD, six-min walking distance; NMES, neuromuscular electrical stimulation; PaO2, arterial oxygen partial
pressure; RV, residual volume; TLC, total lung capacity.
$
Supported by a Research Grant from Fundacão de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Brazil.
Corresponding author. Tel.: +55 11 5571 8384; fax: +55 11 55 75 2843.
E-mail address: [email protected] (J.A. Neder).
1
SDC received a Post-Doctoral Fellowship Grant from FAPESP JAN is an Established Investigator (Level II) of the Conselho Nacional de
Desenvolvimento Cientı́fico e Tecnológico (CNPq), Brazil.
0954-6111/$ - see front matter & 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.rmed.2006.10.023
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Muscle electrical stimulation in COPD
1237
Results: At baseline, patients presented with well-preserved functional capacity, muscle
strength and mass: there was a significant relationship between strength and type II CSA
(Po0.05). NMES was not associated with significant changes in peak torque, LMM or 6MWD
as compared to sham (P40.05). At micro-structural level, however, electrical stimulation
increased type II, but decreased type I, CSA; no change, however, was found in the relative
fibre distribution or capillary:fibre ratio (Po0.05). There was no significant association
between individual changes in structure and function with training (P40.05). Post-NMES
increase in type II CSA was inversely related to baseline mass and strength (Po0.05).
Conclusion: NMES may promote a modest degree of type II muscle fibre hypertrophy in
COPD patients with well-preserved functional status. These micro-strutural changes,
however, were not translated into increased volitional strength in this sub-population.
& 2006 Elsevier Ltd. All rights reserved.
Introduction
Exercise intolerance is a hallmark of advanced chronic
obstructive pulmonary disease (COPD).1 Although much
attention has been paid to the pulmonary-mechanical
abnormalities which actually characterize the disease, new
evidence has demonstrated that skeletal muscle impairment
is centrally related to patients’ functional capacity.2 In
particular, several reports have described significant reductions on muscle mass and strength which responded variably
to selected interventions.3–5
In this context, we,6 and others,7–9 have showed that
high-frequency neuromuscular electrical stimulation (hfNMES) might improve peripheral muscle function with
beneficial consequences on physical capacity in severelydisabled patients. Interestingly, marked changes in strength
after hf-NMES were found in some of them—despite a
training duration that is not commonly associated with a
substantial degree of muscle hypertrophy (6–8 weeks).
These findings raise the question of whether the changes
on strength after hf-NMES would, or not, be related to
enhanced muscle mass. The authors reasoned that by
answering this question we would bring new light on the
controversy about the relationship between muscle structure and function in this patient population.2,10,11
This study was therefore performed to investigate: (i)
whether 6-weeks of NMES would increase isokinetic peak
torque and (ii) the association between hf-NMES-induced
changes in peripheral muscle strength and total and
differential muscle fibre cross-sectional areas in moderately
impaired patients with COPD.
Methods
Inclusion criteria were: dyspnoea on activities of daily
living (Medical Research Council grades II–III),12 absence of
associated locomotor or neurological conditions, arterial
partial pressure for oxygen at rest (PaO2)460 mmHg, and
disease stability as indicated by no change in medication
dosage or exacerbation of symptoms in the preceding 12
weeks. Exclusion criteria were: use of pacemakers, malignancy, cardiac failure, distal arteriopathy, recent surgery,
a1-antiprotease deficiency, severe endocrine, hepatic or
renal disorder, and use of anticoagulant medication. All
patients were optimized in terms of standard medical
therapy: maintenance medication included long- and
short-acting b2-agonists, theophylline, and inhaled steroids.
No patient was receiving oral steroids or chronic domiciliary
oxygen therapy; in addittion, they have never been
submitted to NMES or pulmonary rehabilitation. Informed
consent (as approved by the Institutional Medical Ethics
Committee) was obtained from all patients.
Design and procedures
This was a prospective, cross-over, single-blinded, randomized, and controlled trial (Fig. 1). After study enrollment,
patients were randomly allocated to receive hf-NMES before
sham stimulation or vice-versa: each treatment sequence
lasted for 6 weeks. Pulmonary function, segmental (leg)
body composition, peripheral muscle strength, and 6-min
walking distance (6MWD) were determined at baseline.
These tests were repeated after hf-NMES; post-sham
analysis, however, was restricted to lung function, muscle
strength, and 6MWD evaluations. For ethical reasons,
peripheral muscle biopsy (vastus lateralis) was performed
pre- and post-NMES only.
Patients
Electrical stimulation protocols
Seventeen patients (16 males, aged 57–80) with COPD
according to the GOLD criteria1 were referred from the
COPD outpatient clinics of the São Paulo Hospital (Federal
University of São Paulo, Brazil) for study participation.6
Subjects presented with moderate-to-severe ventilatory
impairment (FEV1o60% predicted in all but one patient).
NMES and sham stimulation were delivered by a portable,
four-channel NME stimulator (Dualpex 961TM, Quark, Brazil).
The electrical current was applied via two self-adhesive
surface electrodes, which were placed longitudinally to the
quadriceps femoris on the motor points.13 During the
stimulation sessions, patients were sitting with legs
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S. Dal Corso et al.
Baseline
evaluation
Sequence 1
Second
evaluation
First
evaluation
NMES
SH
AM
ES
Sequence 2
SHAM
NM
6 weeks
Figure 1
6 weeks
Study protocol.
semiflexed (knee joint at 150–1601): patients were told not
to perform an active voluntary contraction in pace with the
stimulation. During the home-based, 6-weeks, 5 times/week
hf-NMES program, wave frequency and pulse duration were
kept constant (50 Hz and 400 ms, respectively). Stimulation
intensity was individually set to elicit a visible contraction of
the quadriceps (ranging from 10 to 25 mA): this was
increased weekly by approximately 5 mA according to the
patient’s tolerance. The duty cycle (on:off time, %) was
adjusted as follows: week 1 ¼ 2 s:10 s (16%, i.e., 2/12) for
15 min/leg, week 2 ¼ 5 s:25 s (16%) for 30 min/leg, weeks
3–4 ¼ 10 s:30 s (25%) for 1 h/leg, and weeks 5–6: 10 s:20 s
(33%) for 1 h/leg.6,14 The patients returned to the clinic to
adjust hf-NMES parameters (intensity and duty cycle) once a
week. During the 6-week, 5 times/week sham stimulation
period, the following parameters were used: 10 Hz frequency, pulse duration of 50 ms and a current intensity of
only 10 mA. We also certified that these settings were not
sufficiently high to elicit an effective muscle contraction in
all patients.
In order to familiarize the patients with the equipment
and to detect possible side-effects, the hf-NMES training
protocol was initially applied under the guidance of a
qualified and experienced physiotherapist (first week). A
family member was present at the end of this week: he/she
was asked to monitor the training and to secure that the
patient would correctly fill up an user diary with information
regarding the stimulation time, impressions about the
treatment and system settings.
Measurements
Body composition
Total and segmental (right leg) body composition was
assessed by dual energy X-ray absorptiometry (DEXA—Lunar
Radiation Corporation, Madison, WI, USA): leg muscle mass
(LMM, kg) was established according to the differential
degree of photon attenuation at two levels of energy.15
Pulmonary function tests
Spirometric tests were performed by using the CPF SystemTM
(Medical Graphics Corporation—MGC, St. Paul, MN, USA)
with airflow being measured by a calibrated pneumotachograph. The subjects completed at least three acceptable
maximal forced expiratory manoeuvres before and after
400 mg of inhaled salbutamol. Forced vital capacity (FVC)
and forced expiratory volume in 1 s (FEV1) were recorded. A
computer-based automated system (PF-DX System; Medical
Graphics) was used to measure static lung volumes (total
lung capacity and residual volume—TLC and RV, respectively) by the ‘‘breath-by-breath’’ N2 wash-out technique.16
Carbon monoxide diffusing capacity (DLCO) was measured by
the modified Krogh technique (single breath): the subjects
performed two acceptable and reproducible tests, with the
results being within 10% or 3 mL CO/min/mmHg.17
Peripheral muscle strength
Concentric contractions of the quadriceps femoris (knee
extension) of the right leg were evaluated using an
isokinetic dynamometer (Con-TrexTM, Cybex, Chattanooga,
NY, USA). After mild warm-up exercise (typically walking
around the room), positioning and stabilization of the
subjects were standardized. The mechanical axis of rotation
of the lever arm was aligned to the axis of rotation of the
knee. The resistance pad at the end of the lever arm was
strapped to the distal part of the tibia: the exact position
varied according to the patients’ leg length. Correction for
the effect of gravity was made. All patients performed a
maximum isokinetic strength test with 2 trials of 5 movements tested at an angular velocity of 601 s separated by
2 min rest (peak torque, Nm).6,18 The highest value was
selected for analysis.
Muscle biopsy
Open muscle biopsies of the right vastus lateralis were
obtained from its central region, 10–15 cm above the patella
at mid-thigh level. Biopsy sites were anaesthetized previously with 2% lidocaine and 1.5–2.0 cm skin incisions were
made.19 Muscle samples (5–10 g) were divided into two
parts. One was embedded in OCT compound, frozen in
isopentane and cooled in liquid nitrogen for use in fibretyping procedures. The other was immediately allocated in a
tube, frozen and stored at 70 1C until needed. Muscle
sections were obtained in a cryostat and type I and II fibres
were identified using the standard adenosine triphosphatase
stain at different pHs. At least 100 fibres were counted and
measured in each case: median fibre cross-sectional areas
(CSA) were individually measured by a single investigator. In
addition, capillaries around fibres were counted and the
mean was recorded as capillary contacts.
Six-min walking distance
Functional exercise capacity was measured by the 6-min
walking distance test (6MWD) in a 50 m in-hospital corridor.
Technical procedures were those recommended by the
American Thoracic Society:20 oxyhaemoglobin saturation
was checked at the end of the walking by pulse oximetry.
Tests were performed in duplicate and the highest value was
recorded: reference values were those proposed by Enright
and Sherrill.21
Statistical analysis
After certification of data normality (Kolmogorov–Smirnov
test), values are expressed as means7standard deviation
(SD); otherwise, medians and the interquartile range
were used. Repeated measures analysis of variance was
used to investigate the effects of NMES and sham stimulation taking into consideration the treatment sequence.
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1239
Product–moment correlation (Pearson) or Spearman’s correlation coefficient were used to define association between
variables with symetrical or asymetrical distributions,
respectively. The probability of a type I error was
established at 0.05 (Po0.05).
Results
Pre-NMES evaluation
At baseline, patients presented with moderate-to-severe
airflow obstruction and increased static lung volumes
(Table 1). Eleven patients were classified as GOLD
Table 1 Baseline characteristics of the studied population (n ¼ 17).
Variables
Effects of NMES on muscle structure and function
Values (mean7SD)
Demographic and body composition
Age (yr)
Weight (kg)
Height (m)
Body mass index (kg/m2)
Fat-free mass index (kg/m2)
65.976.8
61.3713.3
1.6470.7
22.573.9
17.271.9
Pulmonary function
FVC (L)
FVC (% predicted)
FEV1 (L)
FEV1 (% predicted)
FVC/FEV1
TLC (% predicted)
RV (% predicted)
RV/TLC (%)
DLCO (mmHg/L/min)
DLCO (%)
PaO2 (mmHg)
2.9170.90
80.9719.9
1.4370.50
49.6713.4
51.5720.4
114.2718.4
193.4758.2
55.8711.1
17.275.8
54.5717.9
68.776.6
Definition of abbreviations: FVC ¼ forced vital capacity,
FEV1 ¼ forced expiratory volume in 1 s, TLC ¼ total lung
capacity, RV ¼ residual volume, DLCO ¼ lung diffusing capacity for carbon monoxide, PaO2 ¼ arterial partial pressure for
oxygen.
Table 2
stage III: the remaining 6 patients were on stage II.1 Using
the previously recommended criteria for fat-free mass (FFM)
depletion in COPD (FFM index o15 and 16 kg/m2 for males
and females, respectively),22 only 5 patients were considered as ‘‘FFM-depleted’’. Patients also had well-preserved
functional exercise capacity and muscle strength (Table 1).
Pre-NMES muscle biopsies revealed a paucity of type I
fibres as compared to previously published data in normal
subjects.5,23 In addition, there was a relative atrophy of
type II fibres, i.e., median type II CSA was significantly lower
than type I CSA (Po0.05) (Table 2). We also found a
significant relationship between peak torque and fibre CSA:
this finding was largely due to the high correlation between
type II, but not type I, CSA and strength (Fig. 2). There was
also a highly-significant correlation between LMM by DEXA
with total muscle CSA (type I plus type II) and peak torque
(R ¼ 0.85 and 0.70, Po0.001).
There were no relevant side effects (e.g. skin lesions or
muscle pain) related to NMES application. Based on patient
reports (diaries), the treatment was well-tolerated and
accomplished by all participants. There was a substantial
increase in the self-adjusted intensity of stimulation
throughout the training period: as shown in Fig. 3, average
current amplitude increased from 31 mA in the 1st week to
45 mA at the end of treatment (mean increase ¼ 48.7%).
Considering that the duty cycle also increased from 16% to
33% and the total session duration from 15 to 60 min/leg
(i.e., effective stimulation time increased from 2 to
20 min/session), there was a large increase in the training
workload.
Repeated measures analysis of variance revealed that
there were no significant effect of the treatment sequence
(i.e., NMES before sham and vice-versa) on the main
variables of interest (P40.05). We therefore compared
the effects of the interventions assuming the subjects as a
single group: we found no statistically significant effects of
NMES upon leg muscle mass, peak torque and 6MWD
(Table 2). Similar results were found when the subjects
were separated according to the presence (N ¼ 6) or not of
oxygen desaturation in the 6MWD (SpO2 values ranging from
88% to 94%)(P40.05 for all variables). At the microstructural level, however, there was a significant increase
Effects of sham stimulation and NMES on selected outcomes in patients with COPD (n ¼ 17).
Pre-sham
Post-sham
Pre-NMES
Post-NMES
Peak torque
Absolute (Nm)
% predicted
100.6741.5
86.7738.1
101.8737.7
87.3740.0
93.8743.7
84.3735.3
103.2750.6
88.1742.4
Muscle mass
Absolute (kg)
7.1971.19
7.2571.37
7.3171.25
7.2471.48
Walking distance
Absolute (Nm)
% predicted
497775
98.3717.8
500766
99.0715.2
489778
97.6718.9
502768
99.7714.4
P40.05 for all comparisons (repeated measures ANOVA).
Obs: Cross-over design: Post-NMES is pre-sham for 9 subjects and post-sham is pre-NMES for other 8 patients.
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S. Dal Corso et al.
180
R= 0.61
p<0.01
R= 0.55
p=0.02
Peak Torque (Nm)
160
140
R= 0.22
p>0.05
120
100
Type II CSA
80
Type I CSA
Total CSA
60
1000 2000 3000 4000 5000 6000 7000 8000
Muscle CSA (μm2)
Figure 2 Pre-NMES relationship between total and differential muscle cross-sectional areas (CSA) and strength (peak torque).
Stimulation Intensity (mA)
55
Table 3 Baseline and post- NMES values for microstructural variables in patients with COPD (n ¼ 17).
50
45
40
35
30
25
20
Start
1st
2nd 3rd 4th
Week of Training
5th
6th
Figure 3 Weekly progression on the NMES intensity throughout
the training programme.
in type II, but a decrease in type I, CSA (median change
(range) ¼ 12.5 % (16.8% to 57.6%) vs. 9.8% (40.8 to
36.6%), Po0.05). In contrast, no significant changes were
found on the relative proportion of fiber types or in the
capillary:fiber ratio (Table 3).
In similarity with the pre-training analysis (Fig. 2), there
was a significant, albeit weaker, correlation between posttraining peak torque and type II CSA (R ¼ 0.49, P ¼ 0.04).
More importantly, however, we were unable to find a
significant correlation between % change with training in
type II fiber CSA and % change in peak torque (Fig. 4,
P40.05).
Predictors of improvement after NMES
We found that increase in muscle CSA with training,
especially in type II, was inversely related to baseline mass
and strength (Fig. 5, upper panels). On the contrary,
baseline muscle CSA or strength did not relate to post-NMES
improvement on peak torque (Fig. 5, lower panels).
Pre-NMES
Post-NMES
Muscle histology
Type I fibres
Proportion (%)
Area (mm2)
36.6 (12.0)
4610 (1808)
35.2 (9.3)
4009 (1329)z
Type II fibres
Proportion (%)
Area (mm2)
63.4 (12.0)
3786 (1294)
64.8 (9.3)
4119 (936)z
Type I and II fibres
Area (mm2)
Capillary:fibre ratio
4003 (1294)
1.35 (0.95)
3905 (1026)
1.42 (1.11)
Po0.05 (Wilcoxon test). Data are presented as median
(interquartile range).
Type I vs. Type II.
z
Pre-NMES vs. Post-NMES.
Discussion
This seems to constitute the first study to evaluate the
micro-structural effects of hf-NMES on the peripheral
muscles and their relationships with functional changes in
moderately impaired outpatients with COPD. The main
original findings of the present study can be summarized
as follows: (i) hf-NMES had no discernible effect on muscle
strength, overall muscle mass or walking capacity; (ii)
despite the lack of effect on the functional status,
stimulation was associated with an increase in type II fibre
CSA; and (iii) these micro-structural effects of hf-NMES were
more clearly evident in those patients with diminished
baseline muscle mass or strength. The main clinical message
is that a hf-NMES training program, at least with the settings
used in the present study, has a limited impact upon muscle
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Muscle electrical stimulation in COPD
1241
structure and function in outpatients with COPD with wellpreserved functional capacity.
Electrical stimulation of the locomotor muscles has been
used for decades on different populations, ranging from
% Change in Peak Torque
20
10
0
−10
−20
−20
0
20
40
60
80
% Change in Type II Fibre CSA
Figure 4 Lack of significant correlation between NMES-related
increase in type II CSA and changes in peak torque (P40.05,
Spearman’s correlation).
Δ CSA after NMES (%)
A
B
60
60
40
40
20
p<0.05
0
−20
−20
−40
Δ Peak torque after NMES (%)
p<0.05
20
0
−60
1000 2000 3000 4000 5000 6000 7000 8000
C
elite athletes to bed-bound patients with cancer.14,24,25
Previous authors have found that either low frequency (lf) or
hf-NMES can be effective in some, but not all, circumstances—as recently reviewed by Bax et al.26 More recently,
there has been some renewed interest in establishing new
muscle rehabilitative strategies for patients suffering from
systemic disease states. In the present study, we were
primarily interested in looking at the relationship between
micro-structural and functional changes on the locomotor
muscles after hf-NMES. In this sense, hf-NMES was used as a
non-volitional, hypertrophic-type training to evaluate if
potential changes on muscle mass would be proportionally
related to increased strength. We chose hf-NMES since this
stimulation paradigm has been found to be more effective
than lf-NMES in promoting muscle hypertrophy.24–26 Our
results showed that the small changes on the amount of
contractile protein were largely restricted to type II fibres
(Table 3) but this was not translated into increased strength
(Table 2, Fig. 4).
All of the previous studies using NMES in COPD patients
have evaluated severely- to very-severely disabled subjects.6–9 Although seems to be intuitive to consider passive
exercise only for more frail and incapacited patients,
previous studies suggested that the baseline status of the
skeletal muscle could modulate the effects of NMES, with
Type II
Type I
All fibres
Type II
Type I
All fibres
−40
−60
60
80
100
120
140
160
180
D
20
20
10
10
0
0
NS
NS
−10
−10
−20
1000 2000 3000 4000 5000 6000 7000 8000
CSA before NMES (μm2)
Type II
Type I
All fibres
−20
60
80
100
120
140
160
180
Peak torque before NMES (Nm)
Figure 5 NMES-related changes in muscle cross-sectional area (CSA), especially in type II fibres, were inversely related to baseline
CSA and muscle strength (panels A and B, respectively) (Po0.05, Pearson’s product–moment correlation). Conversely, there was no
significant relationship between NMES-induced changes in muscle strength and pre-treatment CSA and strength (lower panels).
ARTICLE IN PRESS
1242
better results found in subjects with well-preserved muscle
apparatus.14,24–26 Unfortunately, however, our data showed
that despite a positive effect on the amount of contractile
protein in type II fibres, this selective hypertrophy was not
sufficient to increase skeletal muscle strength.
Our data are at variance with previously published studies
on the effects of NMES in COPD.6–9 We believe that the main
reason for these discrepancies is related to differences on
patients characteristics: as mentioned, this is the first study
to have evaluated patients not severely disabled (Tables 1
and 2). Several hypotheses could be raised to explain why
our patients did not respond as well as those evaluated in
the previous studies:6–9 (i) higher stimulation intensity and/
or longer treatment duration would be needed to promote a
measurable effect in this sub-population, (ii) for moderately
impaired patients, a concomitant volitional stimulus (i.e.,
active contraction) could have been more effective than
NMES on isolation, and (iii) non-volitional techniques for
strength assessment could have demonstrated a larger
functional improvement after NMES. In addition, the lack
of association between NMES-induced increase in type II
fibre CSA and strength, despite a significant baseline and
post-training correlation between them, may have been
related to response heterogeneity in this relatively small
sample.
We also found that muscle mass enhancement was
inversely related to baseline values of either mass or
strength (Fig. 5). We interpret these results as additional
evidence that hf-NMES is likely to be more effective in more
frail patients than those who were enrolled in the present
study, e.g., such as those recovering from an acute
exacerbation of COPD. This hypothesis, however, remains
to be properly tested.
An interesting finding of the present study was the
marked atrophy of type I fibres after hf-NMES (Table 3)—a
finding that has been previously described in normal
subjects.27 This could help explain the lack of a significant
effect of hf-NMES on walking capacity; however, as
discussed, it should be recognized that our patients—though
referring dyspnea on daily life—were already relatively
‘‘well-trained’’ at muscular level (Table 2). In this context,
it is intuitive to assume that a reduction on the area of the
fatigue-resistant type I fibres would be associated with a
reduction on the muscle oxidative capacity. However, the
relationhip between type I CSA and muscle oxidative
potential is far from linear: future studies should evaluate
the practical implications of a decrease on type I CSA after
NMES on muscle oxidative profile. Also important is the
notion that the size of type II fibres is more relevant for the
muscle bulk and for strength generating capacity than type I
CSA. Unfortunately, lf-NMES—which seems to be able to
increase the expression of type I fibres28—can induce a
marked atrophy of type II fibres, with important implications
for strength capacity.
This study presents a number of important limitations.
Initiatilly, it remains to be elucidated in which fibre II subtype the observed changes in mass were more relevant. For
instance, there are convincing evidence that hf-NMES can
increase the expression of myosine heavy chain (MHC) IIa in
detriment of MHC-I and MHC-IIx.27 Similarly, we did not
perform a detailed analysis of the myopathological features
or the enzymatic profile of the fibres:29 it would be
S. Dal Corso et al.
interesting to quantify, for example, the residual oxidative
potential of the hypotrophic type I fibres after NMES.30 More
importantly, however, the study could have be underpowered to unravel the effects of a training program in a
population with well-preserved functional capacity at baseline (Table 2).
In conclusion, our data demonstrated that 6-weeks hfNMES was ineffective in enhancing muscle strength and
walking capacity in a group of moderately impaired COPD
patients. Electrical stimulation, however, did increase the
amount of contractile protein in type II fibers, i.e., muscle
structural modifications were not directly translated into
functional improvement.
Acknowledgements
The authors wish to thank: Laura D. Batista, Michelle R. and
Gabriela Siqueira for their skilful technical assistance and
Dircilene P. Moreira for her competent secretarial assistance. In special, the authors are indebted to the patients
for their enthusiastic participation.
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