вход по аккаунту


Effect of physical training on the proportion of slow-twitch type I muscle fibers a novel nonimmune-mediated mechanism for muscle impairment in polymyositis or dermatomyositis.

код для вставкиСкачать
Arthritis & Rheumatism (Arthritis Care & Research)
Vol. 57, No. 7, October 15, 2007, pp 1303–1310
DOI 10.1002/art.22996
© 2007, American College of Rheumatology
Effect of Physical Training on the Proportion of
Slow-Twitch Type I Muscle Fibers, a Novel
Nonimmune-Mediated Mechanism for Muscle
Impairment in Polymyositis or Dermatomyositis
Objective. To compare muscle fiber type composition and muscle fiber area in patients with chronic polymyositis or dermatomyositis and healthy controls, and to determine whether physical training for 12 weeks could alter these muscle characteristics.
Methods. Muscle fiber type composition and muscle fiber area were investigated by biochemical and immunohistochemistry techniques in repeated muscle biopsy samples obtained from 9 patients with chronic myositis before and after a
12-week exercise program and in healthy controls. Muscle performance was evaluated by the Functional Index (FI) in
myositis and by the Short Form 36 (SF-36) quality of life instrument.
Results. Before exercise, the proportion of type I fibers was lower (mean ⴞ SD 32% ⴞ 10%) and the proportion of type
IIC fibers was higher (3% ⴞ 3%) in patients compared with healthy controls. After exercise, percentage of type I fiber
increased to 42% ⴞ 13% (P < 0.05), and type IIC decreased to 1% ⴞ 1%. An exercise-induced 20% increase of the mean
fiber area was also observed. The functional capacity measured by the FI in myositis and the physical functioning
subscale of the SF-36 increased significantly. Improved physical functioning was positively correlated with the proportion of type I fibers (r ⴝ 0.88, P < 0.01) and type II muscle fiber area (r ⴝ 0.70, P < 0.05).
Conclusion. Low muscle endurance in chronic polymyositis or dermatomyositis may be related to a low proportion of
oxidative, slow-twitch type I fibers. Change in fiber type composition and increased muscle fiber area may contribute to
improved muscle endurance and decreased muscle fatigue after a moderate physical training program.
KEY WORDS. Polymyositis; Dermatomyositis; Physical training; Muscle fiber; Muscle function.
Polymyositis and dermatomyositis are chronic inflammatory muscle disorders that are clinically characterized by
Supported by The Swedish Medical Research Council
(2002-74X-14045-02A), The Swedish Rheumatism Association, King Gustaf V’s 80-Year Foundation, Börje Dahlin’s
Foundation, Professor Nanna Svartz’ Foundation, and the
Karolinska Institutet Foundation.
Maryam Dastmalchi, MD, Helene Alexanderson, PhD,
Ingela Loell, BSc, Ingrid E. Lundberg, MD, PhD: Karolinska
University Hospital, Solna, Karolinska Instituet, Stockholm, Sweden; 2Marcus Ståhlberg, BSc, Mona Esbjörnsson,
PhD: Karolinska Instituet, Stockholm, Sweden and Karolinska University Hospital, Huddinge, Sweden; 3Kristian Borg,
MD, PhD: Karolinska Institutet, Stockholm, Sweden.
Address correspondence to Maryam Dastmalchi, MD,
Rheumatology Unit, Karolinska University Hospital, Solna,
SE-171 76 Stockholm, Sweden. E-mail: maryam.dastmalchi@
Submitted for publication May 24, 2006; accepted in revised form March 26, 2007.
muscle weakness, particularly low muscle endurance or
muscle fatigue mainly in proximal muscles such as thigh,
shoulder, and neck muscles (1– 4). Most patients with
polymyositis or dermatomyositis experience at least a partial improvement of muscle function with glucocorticoid
treatment and other immunosuppressive agents (5). However, many patients are left with longstanding low muscle
endurance and reduced quality of life (6,7). The pathophysiologic background to the sustained low muscle endurance and muscle weakness in patients with chronic
polymyositis or dermatomyositis is not known.
In healthy individuals there is a strong relationship between skeletal muscle function and muscle characteristics
such as muscle fiber type composition and cross-sectional
muscle fiber area. Thus, speed of muscle contractions relies mainly on fiber type composition and muscle strength
on cross-sectional muscle fiber area (8 –10). The different
fiber types, fast- or slow-twitch fibers, are classified based
on their content of contractile proteins, fast or slow myosin heavy-chain (11). The relative frequency of fast- and
Dastmalchi et al
Table 1. Summary of patients’ clinical features at first biopsy*
Methotrexate 7.5 mg/week
Prednisolone 5 mg every second day
Prednisolone 3 mg every second day,
azathioprine 100 mg/day
Azathioprine 50 mg/day
Prednisolone 5 mg, azathioprine 100
Prednisolone 2.5 mg/day
Prednisolone 5 mg/day, azathioprine
100 mg/day
Duration with
Duration after
was stopped,
* DM ⫽ dermatomyositis; PM ⫽ polymyositis. Mean age 52 years, median disease duration 44 months.
slow-twitch fibers in a muscle determines its functional
property with respect to strength/power or endurance capacity. Type I fibers (slow-twitch) contain exclusively
slow myosin and possess higher oxidative capacity compared with type IIA and IIB fibers (fast-twitch), which
contain fast myosin (12–16). Type IIC fibers are intermediate fibers because they coexpress both fast and slow
myosin, can develop into either type I or type II fibers
(15,16), and are infrequent in normal adult muscle.
Whether patients with chronic dermatomyositis or polymyositis and persistently reduced muscle function possess
aberrant muscle fiber characteristics that could contribute
to the clinical symptoms has not been investigated previously.
From this perspective, the reported beneficial effects of
exercise in patients with polymyositis or dermatomyositis
are interesting (17–21). Until recently exercise was controversial in patients with inflammatory myopathies due to
fear of exacerbation of muscle inflammation. Now several
studies have demonstrated that moderate exercise in combination with immunosuppressive therapy is safe and also
beneficial to muscle function. The physiologic explanation
for the improved muscle function after training in patients
with myositis has not yet been addressed. In a recent
study, we reported improved muscle endurance with a
training program in a group of patients with chronic polymyositis or dermatomyositis (18). These patients were subject to muscle biopsy before and after the exercise program, and these biopsy findings made it possible for us to
address the question of whether molecular changes such
as muscle fiber characteristics correlated to improved muscle performance. Therefore, the first goal of our study was
to investigate if muscle fiber type composition and muscle
fiber area were different in patients with chronic polymyositis or dermatomyositis with persisting muscle weakness
as compared with age-matched healthy individuals. A second goal was to investigate whether the previously reported improved physical function after a 12-week exercise program was related to any changes in muscle fiber
characteristics (18).
Patients and healthy controls. A total of 8 women and 1
man with chronic polymyositis or dermatomyositis, according to the Bohan and Peter criteria (1,2), who had all
participated in a resistive exercise study were included in
the present study (18). Two of the original 11 patients were
excluded due to insufficient muscle biopsy material. Five
patients were classified as having polymyositis (all
women) and 4 as having dermatomyositis (3 women and 1
man) (1). None of the patients had clinical or histopathologic features compatible with inclusion body myositis
(22). None had diabetes mellitus or uncontrolled thyroid
disease. Clinical and laboratory data have previously been
presented in detail (18). Inclusion criteria were as follows:
clinically stable; inactive polymyositis or dermatomyositis
with a history of remaining muscle weakness; and a duration of immunosuppressive treatment ⱖ12 months, with
no change in immunosuppressive therapy during the 3
months before inclusion in the study (18). Inactive disease
was defined as absence of inflammatory infiltrates in muscle biopsy samples and absence of sign of inflammation on
magnetic resonance imaging (MRI) of thigh muscles. Demographic data and clinical characteristics at the initiation of the study are presented in Table 1. Clinical investigations, muscle biopsy sampling, and MRI were carried
out before and after 12 weeks of a physical exercise program (18). The disease was inactive at both investigations
as assessed by muscle biopsy samples and MRI. Inflammatory infiltrates were absent in all biopsy samples but
one, in which one small isolated perivascular infiltrate
was present without any other histopathologic aberrations (18).
Muscle tissue from vastus lateralis muscle of 11 healthy
individuals, matched for sex (6 women and 5 men, median
age 59 years, range 42–78 years), with no clinical symptoms of muscle weakness and normal muscle biopsy results served as controls for analyses of fiber type composition and fiber cross-sectional area. Due to the limited
Muscle Fiber Composition and Training in Polymyositis/Dermatomyositis
amount of control muscle tissue from healthy individuals,
muscle biopsy specimens from 8 other healthy controls (1
man and 7 women) with a median age of 50 years (range
43– 60 years) were used as control samples for analyses of
regeneration markers.
All patients and controls gave their informed consent to
participate in the study. The study was approved by the
local ethics committee at Karolinska University Hospital.
Methods. Physical training. The training program used
in the present study was based on performing 10 repetitions in several different muscle groups with the intention
to improve muscle endurance. Each patient was individually trained to perform a standardized 15-minute home
exercise program 5 days a week for 12 weeks followed by
a 15-minute walk as previously reported (18). The program
contained a warm-up followed by climbing up and down a
stool, exercise for shoulder mobility and grip strength
with a pulley apparatus, strength exercises for quadriceps and hip muscles, sit-ups without support of the
neck, and careful stretching. For those with small or
moderate reductions of muscle function, weights (0.25–
2.0 kg) were added as well as upper limb strengthening
Assessments. Muscle function. The Functional Index
(FI) in myositis was used for evaluation of muscle strength
and muscle endurance (23). The FI is a disease-specific
index comprising 14 functional tests, which include recordings of the maximum numbers of repetitive movements that can be performed in different muscle groups.
The FI also includes a recording of the number of observed
transfers from side to side and up to a sitting position and
peak expiratory flow (23). The FI is scored from 0 (no
performance) to 64 (full performance).
Perceived health. The Swedish version of the Medical
Outcomes Study Short Form 36 (SF-36) was used to evaluate perceived health-related quality of life (24). The
SF-36 is a generic, self-administered questionnaire composed of 8 subscales: physical functioning, role physical,
bodily pain, general health, vitality, social functioning,
role emotional, and mental health. Each subscale is scored
from 0 to 100, where 100 indicates good health.
Muscle biopsies. Muscle biopsy specimens were obtained from musculus vastus lateralis in the patients, with
the second biopsy specimen, after training, obtained from
the contralateral side. The specimens were obtained under
local anesthesia using a semi-open technique (25). At least
2 tissue samples were taken from each biopsy site. The
samples were frozen in isopentane precooled with dry ice
and stored at ⫺80°C. All muscle biopsy evaluations were
performed on coded slides and the evaluators were
blinded to diagnosis as well as order of the biopsy samples. One of the 2 samples from each biopsy site was
investigated for presence of histopathologic changes including muscle fiber degeneration, regeneration, atrophy,
number of fibers with central nuclei, and inflammatory
infiltrates by an experienced neuropathologist. A second
biopsy sample was used for analyses of muscle fiber characteristics as described below.
Determination of muscle fiber type composition and
muscle fiber cross-sectional area. Histochemical myofibrillar ATPase stainings at pH 4.3, 4.6, and 10.3 were used
to classify muscle fibers into type I, IIA, IIB, and IIC subtypes (9,26). The relative number of the different fiber
types was determined after classification of the fiber types
in ⬃500 fibers in each muscle tissue section.
Fiber type characteristics of type I and type II fibers were
also determined by a standard immunohistochemistry protocol using monoclonal antibodies directed against different isoforms of myosin: anti-slow myosin heavy-chain antibodies (Clone WB-MHCs; Novocastra, Newcastle, UK) for
identification of type I fibers and anti-fast myosin heavychain antibodies (Clone MY-32; Sigma, St. Louis, MO) for
type II fibers (11,13). In this case the relative numbers of
type I and type II fibers were calculated out of ⬃400 fibers
depending on the smaller tissue samples with cross-sectional fibers.
The validity of the ATPase staining was tested by performing a regression analysis between the type I and type
II muscle fiber proportion determined by the ATPase staining versus determined by the immunohistochemistry protocol (type I percentage: r2 ⫽ 0.76, P ⬍ 0.05 and type II
percentage: r2 ⫽ 0.76, P ⬍ 0.05). Cross-sectional muscle
fiber areas of type I and type II were established by calculating the mean value out of the individual area of 20 fibers
of each fiber type per biopsy. This was achieved by applying computerized image analysis (Leica system, BX 60,
Tokyo, Japan; digital camera, Sony CDK-500, Tokyo, Japan) from an NADH staining (27).
Determination of regenerating fibers. Immunohistochemistry was also used to determine signs of regenerating
muscle fibers. We used antibodies toward different markers known to be expressed in different phases of regeneration of the muscle fibers (anti-CD56 antibody [Clone T
199; Dako, Glostrup, Denmark] [28], anti-vimentin antibody [Clone V9; Dako] [29], and anti-neonatal myosin
heavy-chain antibody [Clone Wb-MHCn; Novocastra]
[30,31]) using a standard protocol for immunohistochemistry (32). The whole tissue sections were assessed and the
percentage of positively stained fibers per tissue section
was estimated.
Statistical analysis. Unless otherwise stated, values in
the text are the mean ⫾ SD. P values less than 0.05 were
accepted as statistically significant. Student’s group t-test
and Mann-Whitney test were applied to test the difference
between groups for the muscle characteristic variables before training (basal). Wilcoxon’s signed rank test for paired
observations was applied to test training response for the
clinical variables FI and physical functioning in the patient group. Student’s t-test for paired observations was
applied to test training response for the different fiber
types, CD56 percentage, and vimentin percentage. Regarding cross-sectional muscle fiber area, a 2-factor analysis of
variance (ANOVA; fiber type and time) was applied to test
the difference between fiber type in response to time.
Dastmalchi et al
Single regression analyses were applied to determine the
relationship between training-induced changes in physical functioning versus training-induced changes in proportion of type I fibers and type II cross-sectional muscle
fiber area.
versus 3.9% ⫾ 2.5%) whereas the percentage of vimentin
positive fibers was higher after the training program (0.6%
⫾ 0.9% versus 1% ⫾ 1%; P ⬍ 0.05). The training program
did not change the percentage of fibers expressing neonatal
myosin heavy-chain.
Correlations between exercise-induced changes in muscle fiber characteristics and clinical performance. A positive correlation was found between increase in physical
functioning (a subscale of the SF-36) and increase in the
relative proportion of type I fibers in thigh muscles (r ⫽
0.88, P ⬍ 0.01). A significant correlation was also found
between increase in physical functioning and increase in
type II cross-sectional muscle fiber area (r ⫽ 0.70, P ⬍
Clinical data. Following the 12-week physical training
program, muscle endurance, recorded by the FI score,
increased significantly (mean ⫾ SD FI score 52 ⫾ 12 before
and 58 ⫾ 7 after; P ⬍ 0.05) (Figure 1A). Health-related
quality of life as assessed by the SF-36 physical functioning subscale was also significantly improved by the exercise program in 8 of 9 patients (mean ⫾ SD 58 ⫾ 19 before
and 69 ⫾ 22 after; P ⬍ 0.05) (Figure 1B). The other subscales did not change significantly.
Muscle characteristics at baseline. Fiber type composition by ATPase staining. At baseline, the relative proportion of type I fibers was significantly lower and the relative
proportions of type IIB and IIC fibers were higher in patients compared with age-matched controls (Table 2). The
relative proportion of type IIA did not differ between the
Cross-sectional fiber area. In female patients, type I and
type II cross-sectional fiber area did not differ significantly
from the female controls (Table 2). The male patient’s
cross-sectional muscle fiber area of type I and II was within
the range of the controls’ muscle fiber areas.
Muscle fiber regeneration. Three markers were used to
identify regenerating fibers: CD56, vimentin, and neonatal
myosin heavy-chain. At baseline, only a limited number of
fibers expressed any of these markers and there was no
significant difference between patients and controls. CD56
was expressed in 3.4% ⫾ 3.7% of the fibers of the patients
and in 3.8% ⫾ 6.0% of the fibers of the healthy controls.
The mean ⫾ SD percentage of vimentin positive fibers did
not differ between patients and controls (0.6% ⫾ 0.9% and
0.4% ⫾ 0.5%, respectively). The percentage of fibers expressing neonatal myosin heavy-chain was ⬍0.5% in patients as well as in healthy controls.
Muscle characteristics after training. Fiber type composition. After the 12-week training program, the relative
proportion of type I fibers was 10% higher (P ⬍ 0.05) and
the relative proportion of type IIC fibers was 2% lower
(P ⬍ 0.05) compared with before the exercise program
(Figure 1C and Table 3). The relative proportion of type IIA
and IIB fibers did not change with training.
Cross-sectional fiber area. When applying a repeatedmeasures analysis (ANOVA), a fiber type difference was
revealed regarding exercise-induced changes in cross-sectional muscle fiber area (interaction term: fiber type ⫻
time; P ⬍ 0.05) (Figure 1D and Table 3). A 25% increase of
type II cross-sectional area (P ⬍ 0.05) was observed,
whereas the type I cross-sectional area did not increase
Markers of regeneration. The percentage of CD56 positive fibers was unchanged (mean ⫾ SD 3.4% ⫾ 3.7%
To our knowledge, this is the first study in which muscle
fiber characteristics were investigated in patients with
chronic polymyositis or dermatomyositis. Two main findings were observed. First, the patients were found to have
a lower proportion of type I fibers and a higher proportion
of the intermediate type IIC fibers in comparison with
healthy controls. Second, after a 12-week physical training
program the fiber type composition was closer to normal,
the type II muscle fiber area had increased, and the
changes in fiber type characteristics corresponded to clinical improvements in muscle function.
Several methodologic precautions were taken to standardize and validate the muscle biopsy data. The muscle
biopsy samples were obtained from musculus vastus lateralis, which is classically involved in patients with polymyositis or dermatomyositis and because of its mixed fiber
type composition, trainability, and accessibility. The control samples were also obtained from the same muscle.
Because there are no differences in fiber type composition
between the 2 legs in healthy individuals, the repeat muscle biopsy was performed on the contralateral muscle to
avoid artifacts from the first biopsy (33,34). To exclude a
side-to-side difference as an explanation for the changed
fiber type composition after training, a post hoc analysis
was performed. This did not reveal any significant difference regarding the percentage of type I or type IIC fibers
when comparing right and left limbs in pretraining biopsy
samples (4 randomly obtained from the right leg and 5
from the left leg) or posttraining biopsy samples, respectively, in our patients. Therefore it is unlikely that a sideto-side difference could explain the observed changes of
fiber type composition with training. The ATPase technique is well established for fiber typing and also allows
distinguishing not only between type I and type II muscle
fibers, but also between type IIA, IIB, and IIC fibers. The
fiber type composition was also confirmed by immunohistochemistry. A limitation of the study is the low number of
patients; nevertheless, the fiber type data and changes with
exercise were consistent within the group.
The low percentage of oxygen-dependent type I fibers in
comparison with healthy controls was unexpected, and
there could be several explanations for this finding. One
Muscle Fiber Composition and Training in Polymyositis/Dermatomyositis
Figure 1. Individual changes in patients with chronic myositis after the 12-week exercise program. A, Changes in Functional Index (FI)
score. Sixty-four corresponded to the maximal score of the FI. B, Changes in physical functioning, a subscale of the Short Form 36 Health
Survey. A score of 100 corresponds to full health. C, Individual changes in the proportion of type I and type IIC fibers. D, Individual
changes in muscle fiber cross-sectional area of type I and type II fibers (␮m2). There are missing data for 1 subject in A and B.
explanation could be the level of physical activity. Sedentary individuals in general demonstrate a lower proportion
of type I fibers compared with physically active individuals (35). However, a sedentary lifestyle seems a less likely
explanation, as low physical activity usually is accompa-
nied by type II fiber atrophy, which was not seen in our
patients. Because the controls in our study were healthy
individuals with normal physical activity, we also compared the fiber type composition with published reference
data for healthy, sedentary individuals, and still the pa-
Dastmalchi et al
Table 2. Fiber type distribution and fiber type areas in
vastus lateralis muscle in patients versus controls
before training*
(n ⴝ 9)
Sex, no.
Type I percentage
Type IIA percentage
Type IIB percentage
Type IIC percentage
Type I fiber area, ␮m2
Type II fiber area, ␮m2
Type I fiber area, ␮m2
Type II fiber area, ␮m2
(n ⴝ 11)
32 ⫾ 10
39 ⫾ 12
26 ⫾ 10
4,467 ⫾ 916
47 ⫾ 16†
35 ⫾ 10
15 ⫾ 14†
1 ⫾ 1†
4,694 ⫾ 1,122‡
3,538 ⫾ 798
3,441 ⫾ 1,301‡
4,979 ⫾ 923¶
4,559 ⫾ 909¶
* Values are the mean ⫾ SD unless otherwise indicated.
† Indicates difference between patients and controls at the statistical level of P ⬍ 0.05.
‡ n ⫽ 6.
§ n ⫽ 1.
¶ n ⫽ 5.
tients with myositis had a lower proportion of type I fibers
and a higher proportion of type IIC fibers (12,36). Moreover, deconditioning did not affect fiber type composition
in men with chronic heart failure in comparison with
sedentary men when matched for aerobic capacity (37). All
together, these observations imply that factors other than
low physical activity could contribute to the low proportion of type I fibers in patients with chronic myositis.
Effects of glucocorticoids should also be considered, because glucocorticoids are known to affect both fiber type
composition and fiber area, and especially to cause type
IIB fiber atrophy. All patients in our cohort had been
treated with glucocorticoids over several years, and some
were still receiving glucocorticoid treatment, although in
low doses, at the time of study. However, in patients with
rheumatoid arthritis treated with glucocorticoids, a lower
percentage of type I fibers (36%) was accompanied by a
reduced mean area of both type I and type II fibers, which
was not the case in our patients in whom fiber area was not
decreased (38 – 41). Age and sex are other factors that
could explain aberrant muscle fiber characteristics, but a
decreased percentage of type I fibers has not been reported
as a consequence of age, and, moreover, women tend to
have an increased oxidative phenotype (42).
A possible unexplored explanation for the low percentage of the oxidative type I fibers could be adaptation to
muscle tissue hypoxia. This hypothesis is based on previous observations of a reduced number of capillaries. Furthermore, inflammation by itself may lead to tissue hypoxia (43). Interestingly, a similar low relative proportion of
type I fibers was reported in patients with chronic obstructive lung disease, another condition that gives rise to local
tissue hypoxia (44). Further support for local hypoxia in
muscle tissue is the demonstration of low levels of ATP
and phosphocreatine in muscle observed by magnetic resonance single-photon– emission computed tomography in
patients with dermatomyositis or polymyositis indicating
a metabolic dysfunction, which could be a consequence of
hypoxia (44 – 46).
The seemingly contradictory finding of an increased percentage of type I fibers and at the same time an increased
area of type II fibers after training could possibly have 2
explanations. First, considering the extremely low percentage of type I fibers before training, there should be a
high potential to increase the percentage of the oxidative
fiber type exclusively by the fact that the patients trained 5
days a week at 30 minutes per session for 12 weeks. Second, the exercise program consisted of 2 different components regarding fiber type recruitment; the first component
was 15 minutes of strength/weight training in the arms and
legs with 10 repetitions and the second component was a
15-minute walk. The first part was based on the work load
and number of repetitions. The exact load in percentage of
1 voluntary repetition maximum (VRM) was not calculated; however, the training program was defined as ⬃50%
of 1 VRM. The increased cross-sectional area of type II
fibers and not type I fibers seems reasonable because the
training program to some extent included load training,
and this type of stimulus is known to increase muscle
protein synthesis preferably in type II fibers.
In the present study, muscle function improved with
physical training and a corresponding increase was recorded in the proportion of oxidative type I fibers and type
II cross-sectional area of the thigh muscles. The change in
fiber type composition resulting from the training program
in our study is remarkable, because a change in muscle
fiber type composition after physical training in healthy
individuals is a relatively rare phenomenon (26,47). Muscle fiber type characteristics depend on several components including levels of fast or slow myosin heavy-chain
Table 3. Distribution of muscle fiber type and cross-sectional area in type I and II in patients with chronic myositis before and
after training*
Before training
After training
Interaction: type vs time
Type I%
Type IIA%
Type IIB%
Type IIC%
32 ⫾ 10†
42 ⫾ 13
39 ⫾ 12
34 ⫾ 11
26 ⫾ 10
26 ⫾ 10
3 ⫾ 3†
* Values are the mean ⫾ SD unless otherwise indicated.
† Indicates difference between before and after training at the statistical level of P ⬍ 0.05.
Type I
area, ␮m2
Type II
area, ␮m2
4,570 ⫾ 912
3,658 ⫾ 827†
4,929 ⫾ 1,216
4,555 ⫾ 1,330
P ⬍ 0.05
Muscle Fiber Composition and Training in Polymyositis/Dermatomyositis
proteins, volumes of mitochondria, capillary density, and
oxidative capacity (48). These characteristics are regulated
by a complicated system, which involves multiple signaling pathways and transcription factors (48). The clinical
relevance of the changes in fiber type composition and
fiber area was supported by the improvement of physical
capacity measured by both the FI test and the reported
improvement of physical functioning in the SF-36 questionnaire, which correlated with the increased proportion
of type I muscle fibers and the increased type II crosssectional fiber area.
The mechanisms for the fiber type transition induced by
exercise in patients with polymyositis and dermatomyositis still need to be determined. From our study we can
conclude that it is less likely that the effect on muscle
function and on fiber type characteristics was due to muscle fiber regeneration. A weakness of our study is that we
had to include a second cohort of control individuals to
compare the number of regenerating fibers with the patient
data due to lack of muscle biopsy samples from the first
healthy control cohort. Nonetheless, we find it unlikely
that this would have affected our results regarding changes
in fiber type compositions because only scattered regenerating fibers were seen in the patients’ biopsy samples both
before and after exercise, and a similar low frequency was
seen in the controls. A possible explanation for the improved function and the adaptation of muscle characteristics could be that exercise improved microcirculation in
muscle, lowered total peripheral resistance, and reduced
skeletal muscle ischemia, such as has been reported as a
result of exercise in patients with chronic heart failure
In conclusion, skeletal muscle characteristics that are
related to muscle physiology and muscle performance
were altered in patients with chronic polymyositis or dermatomyositis with persisting muscle impairment.
Whether this is true for patients with myositis in other
phases of the disease still needs to be determined. Although the results are based on a small group of patients,
we believe that low muscle endurance in patients with
chronic myositis could at least in part be explained by a
relatively low proportion of oxidative type I fibers. Furthermore, the beneficial clinical effects of physical exercise could at least in part be explained by molecular
changes within the skeletal muscle.
We are grateful to Ylva Friberg and Eva Lindroos for excellent technical assistance with staining procedures, to
associate professor Inger Nennesmo for histopathologic
evaluation of the muscle biopsy samples, and to associate
professor Christer Malm for the handling/delivering of
antibodies CD56. We also thank associate professor Ronald
Van Vollenhoven for linguistic advice, and professor Lars
Klareskog for critically reading the manuscript.
Dr. Dastmalchi had full access to all of the data in the study and
takes responsibility for the integrity of the data and the accuracy
of the data analysis.
Study design. Dastmalchi, Lundberg.
Acquisition of data. Dastmalchi, Alexanderson, Loell, Borg, Lundberg, Esbjörnsson.
Analysis and interpretation of data. Dastmalchi, Alexanderson,
Ståhlberg, Borg, Lundberg, Esbjörnsson.
Manuscript preparation. Dastmalchi, Alexanderson, Lundberg,
Statistical analysis. Dastmalchi, Esbjörnsson.
1. Bohan A, Peter JB. Polymyositis and dermatomyositis (second
of two parts). N Engl J Med 1975;292:403–7.
2. Bohan A, Peter JB. Polymyositis and dermatomyositis (first of
two parts). N Engl J Med 1975;292:344 –7.
3. Dalakas MC. Polymyositis, dermatomyositis and inclusionbody myositis. N Engl J Med 1991;325:1487–98.
4. Plotz PH, Dalakas M, Leff RL, Love LA, Miller FW, Cronin ME.
Current concepts in the idiopathic inflammatory myopathies:
polymyositis, dermatomyositis, and related disorders. Ann
Intern Med 1989;111:143–57.
5. Henriksson KG, Sandstedt P. Polymyositis: treatment and
prognosis. A study of 107 patients. Acta Neurol Scand 1982;
65:280 –300.
6. Sultan SM, Ioannou Y, Moss K, Isenberg DA. Outcome in
patients with idiopathic inflammatory myositis: morbidity
and mortality. Rheumatology (Oxford) 2002;41:22– 6.
7. Harris-Love MO. Physical activity and disablement in the
idiopathic inflammatory myopathies. Curr Opin Rheumatol
2003;15:679 –90.
8. Barany M. ATPase activity of myosin correlated with speed of
muscle shortening. J Gen Physiol 1967;50 Suppl:197–218.
9. Brooke MH, Kaiser KK. Muscle fiber types: how many and
what kind? Arch Neurol 1970;23:369 –79.
10. Finer JT, Simmons RM, Spudich JA. Single myosin molecule
mechanics: piconewton forces and nanometre steps. Nature
11. Brooke MH, Kaiser KK. Three “myosin adenosine triphosphatase” systems: the nature of their pH lability and sulfhydryl dependence. J Histochem Cytochem 1970;18:670 –2.
12. Essen B, Jansson E, Henriksson J, Taylor AW, Saltin B. Metabolic characteristics of fibre types in human skeletal muscle.
Acta Physiol Scand 1975;95:153– 65.
13. Billeter R, Weber H, Lutz H, Howald H, Eppenberger HM,
Jenny E. Myosin types in human skeletal muscle fibers. Histochemistry 1980;65:249 –59.
14. Hintz CS, Coyle EF, Kaiser KK, Chi MM, Lowry OH. Comparison of muscle fiber typing by quantitative enzyme assays and
by myosin ATPase staining. J Histochem Cytochem 1984;32:
655– 60.
15. Staron RS. Correlation between myofibrillar ATPase activity
and myosin heavy chain composition in single human muscle
fibers. Histochemistry 1991;96:21– 4.
16. Staron RS. Human skeletal muscle fiber types: delineation,
development, and distribution. Can J Appl Physiol 1997;22:
17. Alexanderson H, Lundberg IE. The role of exercise in the
rehabilitation of idiopathic inflammatory myopathies [review]. Curr Opin Rheumatol 2005;17:164 –71.
18. Alexanderson H, Stenstrom CH, Lundberg I. Safety of a home
exercise programme in patients with polymyositis and
dermatomyositis: a pilot study. Rheumatology (Oxford) 1999;
38:608 –11.
19. Alexanderson H, Stenstrom CH, Jenner G, Lundberg I. The
safety of a resistive home exercise program in patients with
recent onset active polymyositis or dermatomyositis. Scand
J Rheumatol 2000;29:295–301.
20. Wiesinger GF, Quittan M, Graninger M, Seeber A, Ebenbichler
G, Sturm B, et al. Benefit of 6 months long-term physical
training in polymyositis/dermatomyositis patients. Br J Rheumatol 1998;37:1338 – 42.
21. Wiesinger GF, Quittan M, Nuhr M, Volc-Platzer B, Ebenbichler G, Zehetgruber M, et al. Aerobic capacity in adult
dermatomyositis/polymyositis patients and healthy controls.
Arch Phys Med Rehabil 2000;81:1–5.
Griggs RC, Askanas V, DiMauro S, Engel A, Karpati G, Mendell JR, et al. Inclusion body myositis and myopathies. Ann
Neurol 1995;38:705–13.
Josefson A, Romanus E, Carlsson J. A functional index in
myositis. J Rheumatol 1996;23:1380 – 4.
Sullivan M, Karlsson J, Ware JE. The Swedish SF-36 Health
Survey. I. Evaluation of data quality, scaling assumptions,
reliability and construct validity across general populations
in Sweden. Soc Sci Med 1995;41:1349 –58.
Henriksson KG. “Semi-open” muscle biopsy technique: a simple outpatient procedure. Acta Neurol Scand 1979;59:317–23.
Schantz P, Randall-Fox E, Hutchison W, Tyden A, Astrand
PO. Muscle fibre type distribution, muscle cross-sectional
area and maximal voluntary strength in humans. Acta Physiol
Scand 1983;117:219 –26.
Novikoff AB, Shin WY, Drucker J. Mitochondrial localization
of oxidative enzymes: staining results with two tetrazolium
salts. J Biophys Biochem Cytol 1961;9:47– 61.
Schubert W, Zimmermann K, Cramer M, Starzinski-Powitz A.
Lymphocyte antigen Leu-19 as a molecular marker of regeneration in human skeletal muscle. Proc Natl Acad Sci U S A
Bornemann A, Schmalbruch H. Desmin and vimentin in regenerating muscles. Muscle Nerve 1992;15:14 –20.
Fitzsimons RB, Hoh JF. Isomyosins in human type 1 and type
2 skeletal muscle fibres. Biochem J 1981;193:229 –33.
Thornell LE, Billeter R, Butler-Browne GS, Eriksson PO,
Ringqvist M, Whalen RG. Development of fiber types in human fetal muscle: an immunocytochemical study. J Neurol
Sci 1984;66:107–15.
Ulfgren AK, Lindblad S, Klareskog L, Andersson J, Andersson
U. Detection of cytokine producing cells in the synovial membrane from patients with rheumatoid arthritis. Ann Rheum
Dis 1995;54:654 – 61.
Blomstrand E, Ekblom B. The needle biopsy technique for
fibre type determination in human skeletal muscle: a methodological study. Acta Physiol Scand 1982;116:437– 42.
Malm C, Nyberg P, Engstrom M, Sjodin B, Lenkei R, Ekblom
B, et al. Immunological changes in human skeletal muscle
and blood after eccentric exercise and multiple biopsies.
J Physiol 2000;529:243– 62.
Simoneau JA, Lortie G, Boulay MR, Thibault MC, Theriault G,
Bouchard C. Skeletal muscle histochemical and biochemical
characteristics in sedentary male and female subjects. Can
J Physiol Pharmacol 1985;63:30 –5.
Toft I, Lindal S, Bonaa KH, Jenssen T. Quantitative measure-
Dastmalchi et al
ment of muscle fiber composition in a normal population.
Muscle Nerve 2003;28:101– 8.
Duscha BD, Annex BH, Green HJ, Pippen AM, Kraus WE.
Deconditioning fails to explain peripheral skeletal muscle
alterations in men with chronic heart failure. J Am Coll Cardiol 2002;39:1170 – 4.
Afifi AK, Bergman RA. Steroid myopathy: a study of the
evolution of the muscle lesion in rabbits. Johns Hopkins Med
J 1969;124:66 – 86.
Danneskiold-Samsoe B, Grimby G. The influence of prednisone on the muscle morphology and muscle enzymes in
patients with rheumatoid arthritis. Clin Sci (Lond) 1986;71:
Edstrom L, Nordemar R. Differential changes in type I and
type II muscle fibres in rheumatoid arthritis: a biopsy study.
Scand J Rheumatol 1974;3:155– 60.
Khaleeli AA, Betteridge DJ, Edwards RH, Round JM, Ross EJ.
Effect of treatment of Cushing’s syndrome on skeletal muscle
structure and function. Clin Endocrinol (Oxford) 1983;19:
Jansson E. Age-related fiber type changes in human skeletal
muscle. In: Maughan RJ, Shirreffs SM, editors. Biochemistry
of exercise IX. Champaign (IL): Human Kinetics; 1996. p.
Kissel JT, Mendell JR, Rammohan KW. Microvascular deposition of complement membrane attack complex in dermatomyositis. N Engl J Med 1986;314:329 –34.
Hildebrand IL, Sylven C, Esbjornsson M, Hellstrom K, Jansson
E. Does chronic hypoxaemia induce transformations of fibre
types? Acta Physiol Scand 1991;141:435–9.
Park JH, Olsen NJ. Utility of magnetic resonance imaging in
the evaluation of patients with inflammatory myopathies [review]. Curr Rheumatol Rep 2001;3:334 – 45.
Park JH, Vital TL, Ryder NM, Hernanz-Schulman M, Partain
CL, Price RR, et al. Magnetic resonance imaging and P-31
magnetic resonance spectroscopy provide unique quantitative data useful in the longitudinal management of patients
with dermatomyositis. Arthritis Rheum 1994;37:736 – 46.
Jansson E, Esbjornsson M, Holm I, Jacobs I. Increase in the
proportion of fast-twitch muscle fibres by sprint training in
males. Acta Physiol Scand 1990;140:359 – 63.
Spangenburg EE, Booth FW. Molecular regulation of individual skeletal muscle fibre types [review]. Acta Physiol Scand
Gielen S, Adams V, Mobius-Winkler S, Linke A, Erbs S, Yu J,
et al. Anti-inflammatory effects of exercise training in the
skeletal muscle of patients with chronic heart failure. J Am
Coll Cardiol 2003;42:861– 8.
Без категории
Размер файла
109 Кб
physical, polymyositis, fiber, muscle, mechanism, dermatomyositis, training, impairments, typed, proportional, slow, mediated, effect, nonimmune, twitch, novem
Пожаловаться на содержимое документа