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140
JACC Vol. 27, No. 1
January 1996:140-5
HEART FAILURE
Relation of Systemic and Local Muscle Exercise Capacity to Skeletal
Muscle Characteristics in Men With Congestive Heart Failure
B A R R Y M. M A S S I E , M D , F A C C , * t A M E R I C O S I M O N I N I , MD,* P U N E E T S A H G A L , MD,*
L A U R E N W E L L S , PT, M S , t G A R Y A. D U D L E Y , PaD~:
San Francisco, California and Athens, Georgia
Objectives. The present study was undertaken to further characterize changes in skeletal muscle morphology and histochemistry in congestive heart failure and to determine the relation of
these changes to abnormalities of systemic and local muscle
exercise capacity.
Background. Abnormalities of skeletal muscle appear to play a
role in the limitation of exercise capacity in congestive heart
failure, but information on the changes in muscle morpholology
and biochemistry and their relation to alterations in muscle
function is limited.
Methods. Eighteen men with predominantly mild to moderate
congestive heart failure (mean + SEM New York Heart Association functional class 2.6 _+ 0.2, ejection fraction 24 -+ 2%) and
eight age- and gender-matched sedentary control subjects underwent measurements of peak systemic oxygen consumption (Vo2)
during cycle ergometry, resistance to fatigue of the quadriceps
femoris muscle group and biopsy of the vastus lateralis muscle.
Results. Peak Vo2 and resistance to fatigue were lower in the
patients with heart failure than in control subjects (15.7 _+ 1.2 vs.
25.1 -+ 1.5 ml/min-kg and 63 -+ 2% vs. 85 -+ 3%, respectively, both
p < 0.001). Patients had a lower proportion of slow twitch, type I
fibers than did control subjects (36 + 3% vs. 46 -+ 5%, p = 0.048)
and a higher proportion of fast twitch, type IIab fibers (18 _+ 3%
vs. 7 -+ 2%, p = 0.004). Fiber cross-sectional area was smaller, and
single-fiber succinate dehydrogenase activity, a mitochondrial
oxidative marker, was lower in patients (both p < 0.034). Like.
wise, the ratio of average fast twitch to slow twitch fiber crosssectional area was lower in patients (0.780 + 0.06 vs. 1.05 -+ 0.08,
p = 0.019). Peak Voz was strongly related to integrated succinate
dehydrogenase activity in patients (r = 0.896, p = 0.001). Peak
Vo2, resistance to fatigue and strength also correlated significantly with several measures of fiber size, especially of fast twitch
fibers, in patients. None of the skeletal muscle characteristics
examined correlated with exercise capacity in control subjects.
Conclusions. These results indicate that congestive heart failure is associated with changes in the characteristics of skeletal
muscle and local as well as systemic exercise performance. There
are fewer slow twitch fibers, smaller fast twitch fibers and lower
succinate dehydrogenase activity. The latter finding suggests that
mitochondrial content of muscle is reduced in heart failure and
that impaired aerobic-oxidative capacity may play a role in the
limitation of systemic exercise capacity.
(J Am Coil Cardiol 1996;27:140-5)
Systemic exercise intolerance and fatigue are common and
troublesome symptoms in patients with heart failure, but their
severity correlates poorly with indexes of cardiac function
(1-3). This discordance appears to be explained in part by
reduced blood flow to exercising muscle (4,5), but evidence
also suggests an important role for abnormalities of skeletal
muscle, including atrophy (6-8), impaired function (9,10) and
altered metabolism (11,12).
To determine the basis for these changes, investigators
(6,13-16) have evaluated morphologic, histologic and biochemical characteristics of skeletal muscle in patients with
congestive heart failure; however, these studies have not
yielded a consistent pattern of abnormalities. Muscle biopsy
findings have also shown variable, if any, relation with measurements of muscle function, muscle metabolism and exercise
capacity. These inconsistencies probably reflect the diversity of
functional and biochemical assessments and the heterogeneity
of the patient and control groups studied.
The present study was undertaken to determine whether
the muscle morphology and histochemistry of patients with
heart failure differs from those of age-matched sedentary
control subjects and, if so, whether these changes are associated with corresponding abnormalities of muscle function and
exercise capacity. To accomplish this, biopsy specimens from
the lateral aspect of the quadriceps femoris were analyzed for
From the *Department of Medicine, Clinical Pharmacology Division and
Cardiovascular Research Institute of the University of California, San Francisco
and ?Cardiology Section and Physical Therapy Service of the Department of
Veterans Affairs Medical Center, San Francisco, California; and SDepartment of
Exercise Science, University of Georgia, Athens, Georgia. This work was
supported in part by Grants KOS-HL02446 and POI-HL25847 (Dr. Massie),
5T32-GM0756 (Drs. Simonini and Sahgal) and NAGW3435 (Dr. Dudley) from
the National Institutes of Health, Bethesda, Maryland; the Department of
Veterans Affai~ Research Service, Washington, D.C. (Dr. Massie); the California Affiliate of the American Heart Association, San Francisco (Dr. Simonini);
and the National Aeronautics and Space Administration, Washington, D.C. (Dr.
Dudley).
All editorial decisions for this article, including selection of referees, were
made by a Guest Editor. This policy applies to all articles with authors from the
University of California, San Francisco.
Manuscript received April 25, 1995; revised manuscript received July 13,
1995, accepted August 1, 1995.
Address for correspondence: Dr. Barry M. Massie, Cardiology Section
(111-C), Veterans Affairs Medical Center, 4150 Clement Street, San Francisco,
California 94121.
© 1996 by the American College of Cardiology
0735-1097/%/$15.(10
(1735-1097(95)00416-5
JACC Vol. 27, No. 1
January 1996:140-5
MASSIE ET AL.
SKELETAL MUSCLE IN H E A R T F A I L U R E
fiber type composition, cross-sectional area, capillarization and
single-fiber succinate dehydrogenase activity, a mitochondrial
marker. These measurements were then related to quantitative
indexes of quadriceps femoris function and systemic exercise
capacity.
Methods
Patients. Eighteen men with a history of stable, chronic
congestive heart failure of >-6 months' duration were recruited
from the Department of Veterans Affairs Medical Center in
San Francisco. The diagnosis was based on a history of dyspnea
on exertion, fatigue or fluid retention, with confirmation of left
ventricular dysfunction by a radionuclide ejection fraction of
<40% (mean : SEM 24 _+ 2%). Symptoms were classified as
New York Heart Association functional class I, II, III and IV
in two, seven, seven and two patients, respectively. Ten patients had ischemic cardiomyopathy, and eight were thought to
have primary myocardial disease. Patients were excluded if
they had had a myocardial infarction within 6 months or if
exercise was limited by symptoms other than fatigue or dyspnea. Other criteria for exclusion included alcohol abuse
within the previous 12 months; initiation of therapy with an
angiotensin-converting enzyme inhibitor, long-acting nitrate,
diuretic drug, or digitalis within 3 months; the presence of
hemodynamically significant valvular disease; angina pectoris;
or exercise limitation by pulmonary, peripheral vascular, arthritic or neurologic disease.
For comparison, eight age-matched sedentary men were
recruited from employees or patients followed up in the
Dermatology Clinic at the Veterans Affairs Medical Center.
These subjects had no history of heart disease and no cardiac,
peripheral vascular or musculoskeletal abnormalities on physical examination. To avoid the comparison of patients with
highly fit control subjects, these subjects were excluded if their
peak systemic oxygen consumption (Vo2) was >1 SD above
the mean for their age. The protocol was approved by the
Committee on Human Research at the University of California, San Francisco; written informed consent was obtained
from all participants.
Physiologic measurements. Systemic exercise capacity.
Peak systemic Vo 2 was quantified during cycle ergometry
according to our previously published techniques (8,10).
Briefly, after resting on the cycle for 5 rain, subjects performed
unloaded exercise for 2 rain. Subsequently, the load was
increased to 200 kg-m/min for 2 rain, and then by 100 kg-m/min
every 2 rain until exhaustion, as defined by the inability to
maintain a pedal frequency of >40 rpm. Standard verbal
encouragement was used for all subjects.
Respiratory gas exchange was monitored by utilizing a
metabolic cart (Sensormedics, Inc.), with measurements of
Vo 2 and carbon dioxide production (Vco2) at 15-s intervals
throughout exercise. Peak systemic Vo2, defined as the highest
Vo 2 achieved, was utilized to quantify exercise capacity, and
the respiratory exchange ratio (VoJVco2) was utilized as an
141
index of the adequacy of exercise. The respiratory exchange
ratio exceeded 1.0 in all patients and control subjects.
Knee extensor function. Knee extensor endurance and
strength were measured with an isokinetic dynamometer (Cybex 340), as described in detail previously (8,10). Briefly, 15
maximal knee extensions were performed at 90% in rapid
succession over a period of -30 s. Verbal encouragement was
given in a standardized manner throughout the procedure.
Endurance, or the ability to withstand fatigue, was defined as
the ratio of the mean peak torque in the last three extensions
to the mean peak torque in the first three extensions multiplied
times 100. The mean peak torque for the first three extensions
was also used as a measure of strength of the quadriceps
femoris muscle group.
Muscle biopsies. Two biopsy specimens were taken from
two different sites, 16 to 19 cm above the patella, by using the
percutaneous needle technique of Bergstrom (17). Specimens
were processed for histochemical analysis as described in detail
elsewhere (18-21). Briefly, sections were assayed for determination of muscle fiber type (I, IIa, Ilab, IIb and IIc) (22),
capillarity and succinate dehydrogenase activity, an estimate of
mitochondrial content.
Area and capillarity of the different fiber types were assessed by using a semiautomated image analysis system and
Image software (National Institutes of Health). From these
data, fiber type percent, the ratio of fast twitch to slow twitch
fiber cross-sectional area, fiber type-specific absolute and
relative areas, average fiber area and the number of capillaries
surrounding a given fiber were calculated. Regions of a section
were excluded from analysis if they contained oblique or
histologically abnormal fibers. At least 150 fibers in each
section were assessed for area, capillarity and type. Data from
the two biopsy sites in each subject were averaged to enhance
validity of the results (23). Type IIc fibers were rare, comprising 2 < 2% overall, and were subsequently excluded from
analyses.
Single-fiber succinate dehydrogenase activity was determined by using a quantitative histochemical technique described by Blanco et al. (24), as done previously (21). Fiber
type-specific activity was determined by matching fibers assayed for succinate dehydrogenase with those in serial sections
assayed for myofibrillar adenosine triphosphatase activity.
About 60 fibers/section were thus assayed. Enzyme activities
for type IIab and type IIb fibers were averaged and reported as
activity for type IIb fibers, because of the low proportion of
type IIab fibers in the control subjects. An adequate number of
matched fibers was available for performing this fiber-specific
analysis in 11 of 18 patients and 7 of 8 control subjects. These
data were used with fiber type percent and average fiber
cross-sectional area to calculate average integrated succinate
dehydrogenase activity irrespective of fiber type, an overall
estimate of mitochondrial content.
Statistical analyses. Comparisons between groups were
made by using an independent analyses of variance with
repeated measures over a given variable or by an independent
t test with SuperANOVA software. Percent and ratio data
142
MASSIE ET AL.
SKELETAL MUSCLE IN HEART FAILURE
JACC Vol. 27, No. l
January 1996:140-5
Table 1. Clinical Data and Physiologic Measurements in 26 Men (18 patients with congestive heart
failure and 8 control subjects)
Age (yr)
Patients
Control subjects
64 + 2
65 -+ 3
NYHA Class
EF (%)
2.6 + 0.2
24 _+2
. . . . . .
Peak Vo2
(ml/kg-min)
Fatigue Index
(%)
Strength
(Nm)
15.7 _+1.2"
25.1 -+ 1.5
63 + 2*
85 _+3
87 _+8
89 _+7
*p < 0.001,patients versus control subjects.Data are presented as mean value + SEM, EF ejection fraction; Nm
Newton-meters; NYHA Class = New York Heart Association functional class; Vo2 = oxygenconsumption;... = data
not available.
were arc-sine or log transformed before analyses. Correlations
between variables were assessed by using Pearson's product
correlations. Data are presented as mean value _+ SEM.
Results
Systemic exercise capacity and local muscle function (Table
1). Control subjects and patients with heart failure were
comparable in age. The heart failure group had a mean
ejection fraction of 24 _ 2% and functional class of 2.6 _+ 0.2.
Although peak Vo2 in the control group was relatively low,
consistent with the age and sedentary status of these subjects,
it was significantly higher than that in patients with heart
failure (25.1 _+ 1.5 vs. 15.7 _ 1.2 ml/kg-min, p < 0.001). The
fatigue index of the knee extensors, calculated from the decline
in peak torque during the series of 15 knee extensions, was
lower in the patients (63 _+ 2% vs. 85 -+ 3%, p < 0.001). In
contrast, knee extensor strength was not significantly reduced
in the patients (87 _+ 8 vs. 89 _+ 7 Newton-meters). Systemic
and local exercise capacity, expressed as peak Vo2 and the
fatigue index, respectively, were correlated in both patients
(r = 0.57, p = 0.026) and control subjects (r = 0.80, p = 0.018).
Muscle biopsy findings (Table 2). The results of the fiber
type analyses and morphometry are given in Table 2. Significant intergroup differences were found in fiber type distribu-
tion. The percent of type I fibers was less in the patients with
heart failure than in the control subjects (36 _+ 3% vs. 46 +
5%, p = 0.048), whereas the percent of type Ilab fibers was
greater in the patients (18 + 3% vs. 7 _+ 2%, p = 0.004).
In both patients and control subjects, type I and IIa fibers
were larger than lib fibers. Overall fiber cross-sectional area
was smaller in patients than in control subjects, reflecting the
smaller size of the fast twitch fibers, because the area of type I
fibers was similar in the two groups. Therefore, the ratio of
average fast twitch to slow twitch fiber area was lower in
patients than in control subjects (0.78 + 0.06 vs. 1.05 -+ 0.08,
p = 0.019).
The hierarchy of succinate dehydrogenase activity reflected
the usual type I > type IIa > type lib pattern in both groups,
but the mean activity per fiber was reduced in the patients
(100 z 5 vs. 119 +_ 9 optical density U/min x 10 -4, p = 0.026),
reflecting lower values in all fiber types. The number of
capillaries around a given fiber followed the hierarchy of type
I or type IIa > type llab or type IIb. However, the number of
capillaries per fiber did not differ between groups for any type
of fiber.
Relation of exercise capacity to muscle characteristics.
The finding that the patients with heart failure and control
subjects differed in both distribution and size of fiber types
necessitated that skeletal muscle characteristics be weighted
Table 2. Skeletal Muscle Morphology and Histochemical Findings in the 26 Study Subjects
Fiber Type
I
Distribution (%)*t
Patients (n = 18)
Control subjects (n = 8)
Mean cross-sectional area (/,mZ)§t
Patients
Control subjects
Succinic dehydrogenase activity§t
(optical density U/min × 10 4)
Patients
Control subjects
Capillaries per fibert
Patients
Control subjects
36 _+3:~
46 -+ 5
IIa
25 + 4
28 -+ 5
llab
18 _+3*
7 -+ 2
lib
22 _+4
17 -- 4
6,031 _+615
5,874 _+487
5,598 _+647
7,200 _+ 1,001
4.792 + 644
5,986 _+971
3,413 +_409
5,309 _+867
130 _+7
143 _+13
94 _+8
123 _+12
II
II
76 _+8
91 _+14
4.2 + 0.2
4.2 _+0.2
3.7 _+0.2
4.1 + 0.3
3.3 _+0.3
3.4 _+0.4
2.9 + 0.2
3.2 _+0.3
*Fiber type by group interaction by analysis of variance (ANOVA), p = 0.022; tfiber type by ANOVA, p < 0.043;
Sp < 0.05, patients versus control subjects;§group effectby ANOVA, patients versus control subjects,p -< 0.034; Ilsuecinic
dehydrogenase activity not given for Ilab fibers because of small numbers. Data are presented as mean value z SEM.
JACC Vol. 27, No. 1
January 1996:140-5
3O
MASSIE ET AL.
SKELETAL MUSCLE 1N HEART FAILURE
r=O.90
p<0.001
.c_ 25
E 20
•
i
0> 1 0
-~ 5
a_
0
0
20
40
60
80
100
Integrated SDH (od units x um2)
120
Figure 1. Plot shows a strong relation between integrated succinate
dehydrogenase(SDH) activityand peak oxygenconsumption(VO2) in
the patients with congestiveheart failure (r = 0.90, p < 0.001). od =
optical density.
for these variables when making comparisons between biopsy
findings and exercise capacity. For example, the lower percent
of type I fibers in patients was partially offset by the finding that
their slow twitch fibers were relatively larger than their fast
twitch counterparts as compared with observations in control
subjects.
In the heart failure group, peak Vo 2 correlated with
average fiber area (r = 0.67, p = 0.007), primarily reflecting
the close correlation with fast twitch fiber area (r = 0.68, p =
0.006). As shown in Figure 1, the relation between peak Vo2
and integrated succinate dehydrogenase activity was very close
(r = 0.90, p < 0.001). Peak Vo2 did not correlate with any
measures of fiber size in the control subjects (r values all
<0.50, p values all >0.20), nor did it correlate with succinate
dehydrogenase activity in this uniformly sedentary older patient group (r = 0.28, p = 0.639).
The knee extensor fatigue index correlated significantly
with average fast twitch fiber area and the ratio of the fast
twitch to slow twitch fiber area in the patients with heart failure
(r = 0.57, p = 0.043 and r = 0.56, p = 0.037, respectively). The
relation between the fatigue index and succinate dehydrogenase activity was of borderline significance (r = 0.53, p =
0.082). The fatigue index did not correlate with any quantitative muscle biopsy measurement in the control group. Knee
extensor strength was correlated to average fiber area (r =
0.54, p = 0.046) and the average fast twitch fiber area (r = 0.57,
p = 0.043) in patients but to none of these variables in the
control group.
Discussion
Major findings of the present study. Several findings in this
study provide additional insight into the pathophysiology of
skeletal muscle dysfunction and exercise intolerance in patients with heart failure. First, they build on previous reports
that have demonstrated a decreased proportion of slow twitch
oxidative fibers and reduced aerobic-oxidative enzyme content
in such patients (6,13-16). In addition to these findings, our
results show that the lower mitochondrial content is not
specific to fiber type but is evident for each of the major fiber
143
types of human skeletal muscle, as reflected by single-fiber
succinate dehydrogenase activity. Second, the strong relation
between average integrated succinate dehydrogenase activity,
a cumulative index of mitochondrial aerobic-oxidative enzyme
content, and peak Vo2 in patients with heart failure, but not in
control subjects, suggests that the impairment of aerobicoxidative capacity may be physiologically significant and contribute to exercise limitation. Finally, several of our findings in
patients with heart failure differ from the characteristic responses to muscle disuse in healthy sedentary individuals
(20,25-28).
Skeletal muscle characteristics in heart failure. Several
groups have reported a lower aerobic-oxidative enzyme content in homogenates of skeletal muscle from patients with
heart failure, irrespective of the indexes measured (6,13-16).
In contrast, this study quantified succinate dehydrogenase
activity in single-muscle fibers in relation to their contractile
material. This technique affords the opportunity to determine
mitochondrial content in the three major fiber types of human
skeletal muscle and eliminates the potential for extraneous
factors, such as extracellular fluid accumulation or fatty infiltration, to affect measures of enzyme activity. As is the case in
normal subjects (21,29), aerobic-oxidative enzyme activity in
the patients with heart failure showed a hierarchy among fiber
types, with type I > type IIa > type lib, However, irrespective
of fiber type, the succinate dehydrogenase activity of patients
was lower than that in control subjects. Thus, the reduction in
oxidative enzyme activity was not specific to one group of
fibers.
The results of this study also extend previous observations
concerning differences in fiber type composition between
patients with heart failure and control subjects. The previously
reported finding (14,15) that such patients have a lower
proportion of type I, slow twitch fibers and more type 2b, fast
twitch glycolytic fibers than do normal subjects was also
evident in this study. In addition, we subclassified fast twitch
fibers into three types, because it is now evident that fibers that
stain intermediate between types IIa and lib, and are thus
distinct from their counterparts (22). Our results suggest that
the higher proportion of type lib fibers reported previously in
patients with heart failure may have been due to a higher
proportion of type IIab fibers. These findings suggest transition
to skeletal muscle with a lower aerobic-oxidative enzyme
content because type IIab or type IIb fibers have lower
succinate dehydrogenase activity than do type I or type IIa
fibers (21). The mechanisms responsible for the different fiber
type composition of skeletal muscle between patients and
age-matched sedentary control subjects is not known, but
preferential loss of type I fibers through denervation or
transformation from slow to fast fibers, as may occur with
muscle disuse, may be responsible (30,31).
The majority of previous studies (6,13-16) have reported at
least a trend toward smaller type II fibers in patients with heart
failure than in control subjects. We found that, irrespective of
fiber type, fibers were significantly smaller in patients than in
control subjects; in addition, the lower ratio for the cross-
144
MASSIE ET AL.
SKELETAL MUSCLE IN HEART FAILURE
sectional area of fast to slow fibers in patients indicates that
atrophy is relatively specific to fast fibers. Findings concerning
skeletal muscle capillarization in patients with heart failure
have been variable (13-15). We found no difference between
groups in the number of capillaries surrounding a given fiber
type, but the maintenance of a normal capillary density is of
interest because a reduction in proportion to the decrease in
mitochondrial content is more typical in normal subjects.
Functional and metabolic correlates of the muscle biopsy
findings. Data relating histologic characteristics of skeletal
muscle to exercise capacity are limited and conflicting. Mancini
et al. (13) reported that peak Vo2 and type I fiber percent were
positively correlated, whereas peak Vo 2 and type lib fiber
percent were inversely related. Lipkin et al. (6) did not find any
significant correlations between knee extensor strength and
several skeletal muscle characteristics despite abnormalities in
both. We found that peak Vo 2 correlated with average fast
twitch fiber and overall fiber cross-sectional area in patients
with heart failure, as did the fatigue index and strength of the
knee extensors. No such correlations were found in the control
subjects. Whether these findings have mechanistic significance or represent associations with other factors remains
uncertain.
Data relating exercise performance or metabolism to the
content of oxidative enzymes also have shown mixed results.
We found a strong correlation between peak Vo 2 and integrated succinate dehydrogenase activity in patients with heart
failure (r = 0.90, p < 0.001), but not in control subjects.
Although Mancini et al. (13) did not observe a relation
between these variables, or between aerobic-oxidative enzyme
content and phosphorus-31 magnetic resonance spectroscopy
indexes of metabolism, in rats with experimental heart failure,
citrate synthase activity and phosphocreatine content during
repetitive stimulation of the gastrocnemius muscle were significantly correlated (32). Drexler et al. (15) and Munzel et al.
(33) have reported a significant relation between skeletal
muscle mitochondrial content and leg oxygen extraction, and
parallel increases in these measures during chronic angiotensinconverting enzyme inhibitor therapy.
Thus, our data, in conjunction with previous findings demonstrating that in some patients blood flow to exercising
muscle does not limit oxygen uptake, are consistent with the
hypothesis that the low mitochondrial content of skeletal
muscle in heart failure influences exercise capacity (34,35).
This is especially noteworthy for systemic exercise performance, which in healthy subjects is determined primarily by
cardiac reserve (36). However, other factors are also likely to
be involved in local muscular exercise intolerance in the
patients. We found a 40% decrease in force during 30 s of
repetitive knee extensions in this and a previous study (10).
Patients with heart failure have also shown (37,38) a similar
decline in force during isometric ankle flexion or knee extension. Fatigue was rapid and severe whether intermittent blood
flow was allowed during knee extensions or blood flow was
occluded (10), suggesting that during these local muscle protocols, nonmetabolic factors may also play a role. Such factors
JACC Vol. 27, No. 1
January 1996:140-5
may include failure of excitation-contraction coupling (39),
inefficiency of chemical to mechanical energy transduction (40)
or reflex inhibition of motor unit activation, alone or in
combination.
Exercise intolerance in congestive heart failure and muscle
disuse. Since skeletal muscle abnormalities have been recognized in heart failure, a major issue has been whether they
occur solely as a secondary consequence of the diminished
activity accompanying this condition or whether they are a
direct consequence of the syndrome and an additional factor in
propagating exercise intolerance (41). Several findings in this
study provide circumstantial evidence that a process in addition to muscle disuse is being expressed. First, reduced
strength and muscle atrophy are the characteristic responses to
inactivity (28), with disuse consistently evoking greater relative
decreases in strength than in muscle size (20,25,27,28). In
contrast, patients with mild to moderate heart failure exhibit
significant atrophy but relatively well preserved strength
(8,10, present study). Second, as discussed previously, patients experience rapid and extreme local muscular fatigue
(10, present study). In normal subjects, forced inactivity that
reduces mitochondrial content by 15% to 20%, the difference noted between patients and control subjects in this
study, evokes only a slight decline ( - 6 % ) in the ability to
withstand fatigue (27). Third, patients with heart failure
showed a markedly lower ratio of fast twitch to slow twitch
fiber size than did control subjects in this study, suggesting
atrophy mainly of fast twitch fibers, as other investigators
(6,13-16) have noted. In contrast, this ratio is not altered by
muscle disuse in healthy subjects, who exhibit comparable
atrophy of all fiber types (20,25,26). Although no definitive
conclusions can be drawn from these observations, these
findings suggest that as yet undefined factors are responsible
for some of the changes in muscle function and protein
expression in heart failure.
Implications of this study. The results of this study provide
additional insight into previous demonstrations of abnormal
skeletal muscle function, metabolism and composition in patients with congestive heart failure. They support the concept
that reduced aerobic-oxidative capacity and possibly other
factors contributing to extreme local muscular fatigue play a
role in their exercise intolerance. Although it is not possible to
conclude from the present results that these changes are
specific for the syndrome of heart failure or to define the role
of muscle disuse in their genesis, at least some of the abnormalities appear not to be characteristic of inactivity alone.
Additional studies are required to differentiate the contributions of heart failure from those of chronic illness and inactivity
in the pathophysiology of skeletal muscle dysfunction in this
syndrome.
We gratefully acknowledge the assistance of Susan Ammon, RN and Kimberly
Prouty, RN in performing the tests, and the technical and statistical assistance of
Bruce M. Hather, PhD, Robert T. Harris, PhD, Michael S. Conley, MS and Sue
Loffek. We especially thank the patients and control subjects who volunteered
for this study.
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SKELETAL MUSCLE IN HEART FAILURE
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