Muscle Mutability
Part 1. General Concepts and Adaptations to Altered Patterns of Use
STEVEN J. ROSE
and JULES M. ROTHSTEIN
During the past two decades investigators have shown that muscle fiber is highly
mutable. A variety of stimuli ranging from patterns of use to the nutritional state
of the organism may lead to alterations in fiber structure and function. The
purpose of this review is to provide the information necessary to understand
muscle fiber mutability (ie, terms and muscle fiber classification schemes) and
to critically review the literature about mutability in response to altered patterns
of use. The relevance of these studies to physical therapy is discussed, and
suggestions for clinical applications are made.
Key Words: Motor units; Muscle fiber types, predominance of; Muscle mutability.
During the past 20 years animal and human studies
have demonstrated that the muscle cells (fibers) of
the skeletal motor unit have adaptive potential.1"3
This capacity of muscle fibers to adapt is remarkable
in view of the muscle cell's high degree of biological
specialization.4 Muscle is probably the most adaptable
tissue in the body in response to a wide variety of
stimuli involving patterns of use, pathological conditions, drugs, or metabolic factors. Many of the
changes experimentally produced in muscle have
been accomplished through procedures used in physical therapy, such as electrical stimulation, immobilization with cast, and exercise. The results of musclemutability experiments provide knowledge that can
be used to develop guidelines for the more precise
application of these treatment modalities. Clinically
useful knowledge may also be gained from the work
of investigators who have used animal models to
mimic clinical conditions, such as disuse atrophy. In
addition, researchers have examined the changes that
take place in human muscle as a result of various
diseases, metabolic conditions, and aging.5"8 Knowledge of muscle mutability allows the therapist to
devise scientifically based treatment programs for
correcting and preventing movement dysfunction.
The purpose of this review is to present a selected
summary of the vast body of literature pertaining to
muscle fiber mutability in response to patterns of use
and disuse. The response of muscle fibers to other
stimuli, such as aging, drugs, and metabolic factors,
are discussed elsewhere in this issue. However, to
understand mutability of muscle fibers, regardless of
the cause, an understanding of muscle fiber classifiVolume 62 I Number 12, December 1982
cation schemes and terms (eg, muscle fiber predominance) is essential. Knowledge of fiber classification
schemes and of concepts such as predominance is
needed for scientifically based clinical practice because therapeutic procedures apparently can lead to
rather selective changes in different types of motor
units.1'9'10
MUSCLE FIBER CLASSIFICATION SCHEMES
A skeletal motor unit consists of a single alpha
motoneuron and all the muscle fibers innervated by
its axon.11 The innervated skeletal muscle fibers of
the motor unit have been termed the muscle unit.12 A
skeletal muscle, such as the biceps brachii or the
quadriceps femoris, is made up of muscle units. A
muscle unit is always associated with a specific type
of motoneuron.13"16 The pairing of muscle units and
neurons with complementary physiological properties
produces a functionally unified biological element.12
For example, muscle fibers that are fatigue-resistant
and can sustain tension for long periods of time are
matched with motoneurons that are frequently activated.12 Through the use of standard histochemical17, 18 and biochemical19, 20 techniques, muscle
biologists have demonstrated that in the absence of
disease or injury, all muscle fibers within a motor
unit are apparently identical. Therefore, muscle units
are homogeneous. Each skeletal muscle, however, is
heterogeneous; that is, it is composed of different
types of muscle units.21
When mammalian muscle was shown to contain
musclefiberswith different anatomical, physiological,
1773
Figure. Staining characteristics of human muscle fibers as regards myosin ATPase. Comparisons of serial sections
allow for the classification of fibers into four categories: type I, the only dark staining fiber at the lowest pH; type HA,
the only fiber that does not stain at a pH of 4.6; type IIB, the fiber that stains at a pH of 4.6 but not at a pH of 4.3; and
type IIC, the fiber that stains intensely at pH levels of 10.3 and 4.6 but only moderately at a pH of 4.3.
histochemical, and biochemical properties, the need
to classify motor units and muscle units became essential. During the past 20 years, many schemes have
been used to characterize the differences between the
various kinds of units. Although there has been controversy and confusion concerning the validity or
interpretation of the proposed classifications, three
schemes seem to have gained the most acceptance.
The differences between the schemes lie in the use
of different variables for the classifications. Peter and
colleagues examined muscle only and classified fibers
(muscle units) according to biochemical, physiological, and histochemical properties.22 In contrast, Burke
examined entire motor units and based his classification scheme on the physiological properties of the
motoneuron and muscle fibers, as well as on the
histochemistry of identified muscle fibers.12 Brooke
and Kaiser used only histochemistry to classify fibers.23
Peter et al developed their classification scheme
using whole and relatively homogeneous muscle.22
They studied animal muscles that consisted mainly of
a single fiber type and compared the biochemical,
histochemical, and physiological elements of these
different "pure" muscles. Three classes of fibers were
1774
described based on contraction times and enzyme
capacities, specifically oxidative and glycolytic enzymes: 1) fast-twitch, glycolytic (FG); 2) fast-twitch,
oxidative, glycolytic (FOG); and 3) slow-twitch, oxidative (SO).
Over a seven-year period, Burke conducted a series
of important experiments on cat motor units that
resulted in the formulation of another classification
system.12 Triceps surae muscle motoneurons in the
ventral horn of L7 and SI spinal cord segments were
impaled with micropipette electrodes. To physiologically characterize and identify motoneurons, synaptic
potentials were recorded in response to natural or
electrical stimulation of specific input systems. Concurrently, the mechanical properties of the identified
motor unit were studied by passing a depolarizing
current through the electrode to cause contraction of
the muscle unit. These contractions were recorded by
a force transducer attached to the muscle's tendon
and could then be characterized.
Using the glycogen depletion method, Burke examined the histochemical profiles of physiologically
identified motor units.12 This technique permits histochemical identification of the activated muscle unit
by depleting its supply of glycogen through prolonged
PHYSICAL THERAPY
TABLE
Muscle Fiber Classification Systems
Brooke/Kaiser
Peter et al 22
Burke12
23
Nomenclature
Basis for Classification
Classification System
Histochemistry
Myofibrillar ATPase (pre-incubations pH
10.3, 4.6, 4.3)
Histochemistry
Oxidative enzymes
Glycolytic enzymes
Myofibrillar ATPase
Physiology
Contraction characteristics of whole muscle
Biochemistry (whole muscle)
Physiology
Contraction characteristics of motor units
identified by glycogen depletion
stimulation of the motoneuron. The glycogen-depleted muscle fibers (activated fibers) are then analyzed for their histochemical profiles. Data on motoneuronal properties were correlated with individual
muscle unit contractile and histochemical characteristics. Burke divided the motor unit population into
four categories: 1) fast-twkch, fast-fatigable (FF); 2)
fast-twitch, intermediate fatigue-resistant (FI); 3) fasttwitch, fatigue-resistant (FR); and 4) slow-twitch, fatigue-resistant (S).
Brooke and Kaiser developed a classification
scheme that has become the standard method for
classifying human muscle fibers.23 Their system is
based on the pH lability of the myosin adenosinetriphosphatase (ATPase) enzyme. It was observed by
Engel that type I fibers exhibit light staining after an
alkaline preincubation, whereas type II fibers stain
darker at the same alkaline pH level.6 Brooke and
Kaiser demonstrated that with manipulation of the
pH level of the preincubation medium, the following
type II subclasses can be shown: IIA, IIB, and IIC.
Type IIA fibers do not stain at a pH level of 4.6,
whereas a pH level of 4.3 is required to inhibit the
staining of the type IIA and IIB fibers. In general,
the only fiber that stains intensely at an alkaline and
an acid pH level is the type IIC fiber (Figure ).
Because all the classification systems use different
criteria for assigning names to muscle units and motor
units, there is no clear-cut equivalence of units described by the different systems. Creating an equivalence table of all the fiber types would at present have
questionable validity, and this is especially true for
the subclasses of the type II fibers. However, to make
generalizations and to avoid confusion in understanding the literature, a description of the relationships
between the classifications is useful.
The following is a generally accepted way of correlating the nomenclature and a brief description of
the biological properties of each muscle fiber type
(Table):
Volume 62 / Number 12, December
1982
I
MA
IIB
SO FOG
s
FR
IIC
FG
Fl
FF
1) Type I (SO, S) fibers have large amounts of
oxidative enzymes and small amounts of glycolytic
enzymes. These fibers primarily use aerobic metabolism, are associated with extensive capillary density,
have a high number of mitochondria, and have wide
Z bands.24, 25 These muscle units generate a relatively
small amount of tension, have a slow contraction
speed, and are resistant to fatigue.
2) Type IIB (FG, FF) fibers are well-supplied with
glycolytic enzymes and are poorly endowed with
oxidative enzymes, which indicates a high capacity
for anaerobic metabolism. These fibers are associated
with relatively sparse capillary density, have few mitochondria, and have narrow Z bands.25, 26 These
muscle units generate a large amount of tension in a
short time, but they fatigue rapidly.
3) Type IIA (FOG, FR) fibers possess intermediate
amounts of oxidative and glycolytic enzymes, which
indicates the use of both anaerobic and aerobic metabolism. These fibers have cytological properties that
fall between the type I and type IIB fibers.26 These
muscle units have relatively fast contraction speeds
and intermediate tension-generating capacity and are
resistant to fatigue.
Two of the classification schemes—Burke's, based
on a cat muscle and Brooke and Kaiser's, based on
human muscle—include a third subclass of type II
fiber. Burke describes a fast-twitch unit with intermediate fatigue resistance (FI). The Brooke and Kaiser classification includes a type IIC fiber. Regardless
of the classification scheme used, these fibers usually
make up a small percentage of the total fiber populations. Very little is known about the FI or type IIC
fibers, and it is not clear whether they are the same.
In an attempt to describe the general characteristics
of muscle units, we have, by necessity, made some
assumptions. These descriptions are based on observations of untrained human and animal muscle. As
will be discussed later in this review, some of the
metabolic properties of muscle can be modified with
1775
altered patterns of use. Some authors prefer to use the
myosin ATPase approach of classification because it
is least affected by training-induced changes. Saltin
et al discussed at length some of the difficulties that
occur when classification of fibers is based on metabolic enzymes.26
MUSCLE FIBER TYPE PREDOMINANCE
The distribution of motor units in humans is very
different from that in animals. In animal muscle there
are many muscles that have a predominance of either
fast- or slow-twitch units and this is true for any
member of that species; for example, in all rats, the
soleus muscle is slow. In humans this does not appear
to be the case. The proportion of fibers of any given
type varies greatly between individuals (one person
may have a greater percentage of slow-twitch units in
their vastus lateralis muscle than another person
has).21 However, when muscles of many people are
examined and the fiber proportions are averaged, the
ratio of fast- to slow-twitch fibers is usually 50:50.21
Humans, therefore, tend to have almost equal numbers of the two major fiber types in most muscles.
When the muscles of an individual are compared,
variability between muscles is observed; the fiber
proportions in the vastus lateralis muscle, for example, may be very different from the proportions in the
rectus femoris muscle of the same subject.21
Muscle fiber type predominance is said to exist
when the percentage (number of fibers) of a given
muscle unit type is extremely large within a specific
muscle or when compared with another muscle.7 Existing evidence suggests that muscle fiber type predominance is genetically determined.27 When predominance of one fiber type has been demonstrated
in a muscle, for convenience the whole muscle has
been referred to as "fast" or "slow."
Clinical Significance
Muscle fiber type predominance has become an
issue in sports medicine. Athletes often have a high
proportion of a fiber type that allows them to excel in
their particular sport.26-35 Marathon runners, for example, have a high proportion of slow-twitch muscle
units.26 However, there is general agreement that
other factors, such as motivation, coordination, and
learning may be equally important for athletic success.28, 35 Whether training can induce a change in
fiber type predominance is still unresolved.
Theoretically, muscle dysfunction may give rise to
joint dysfunction, which may make fiber type predominance important clinically. For example, an individual who has a low proportion of slow-twitch
muscle units might be susceptible to joint injury when
performing tasks that require endurance. The muscle
1776
may fatigue and be unable to protect the joint from
excessive loading. On the other hand, an individual
with a low proportion of fast-twitch units might have
a decreased capacity to produce a fast rise in tension
in response to sudden loads. This failure to develop
tension rapidly might lead to excessive joint loading,
causing joint destruction.
Although the above hypotheses are speculative at
present, they are based on concepts derived from
experimental data. Radin, in his work done with
others, demonstrated that the most destructive forces
applied to cartilage are impulse loads.36 These loads
require cartilage to absorb shock at a rate beyond its
capability. Radin has postulated that impulse loading
may be a major cause of osteoarthritis (or osteoarthrosis as he prefers to call it because of its noninflammatory origin). He also concluded that it is the shockabsorbing quality of muscle action that prevents cartilage destruction by impulse loading. The eccentric
contraction, which Hill described as doing negative
work,37 appears to be the mechanism that is used to
save cartilage from the effects of impulse loading. In
view of the suggested role of muscle in sparing cartilage, we believe that muscle must be capable of welltimed and appropriately modulated contractions.
According to the model proposed by Radin, without the appropriate amount and rate of tension development, joint destruction would be almost assured.
Sirca and Susec-Michieli examined the muscle fibers
of subjects with osteoarthritis.38 Those authors do not
discuss the possibility that their finding a loss of type
II fibers is a potential cause rather than a result of the
disease. We must emphasize the word "potential"
because the notion that inappropriate fiber predominance might lead to osteoarthrosis is highly speculative. However, it is a intriguing thought and points
out the importance of considering how inadequate
muscle performance could contribute to a mechanical
disruption of joints. Research is needed before a
definitive link can be shown between patterns of
muscle fiber predominance and joint dysfunction.
However, others have also suggested inappropriate
muscle action may be a cause of joint pain.39-42 Until
research determines whether a link does exist, we
advise clinicians to consider the possible contribution
of muscle to joint dysfunction.
MUTABILITY PARADIGMS
Although many experimental paradigms have been
used to alter the properties of muscle fibers, these
experimental approaches can be grouped into four
major categories. One paradigm places muscle fibers
in a state of reduced activity or disuse.43, 44 The assumption is made that the muscle fibers are then
experiencing a decreased metabolic demand. Immobilization, tenotomy, and the elimination of descendPHYSICAL THERAPY
ing influences on lower motoneurons are examples of
procedures used to eliminate or reduce activity in the
motor units.45, 46 The second experimental model is
one in which there is increased use of the muscle
fibers.4'46 In this case, there is an increase in the
metabolic demand placed on the muscle fibers. Electrical stimulation, exercise, and compensatory hypertrophy produced by denervating one muscle of a
synergistic group are methods used to produce increased use of a muscle.4, 10, 46 The third paradigm
involves the use of drugs such as anabolic and catabolic steroids.47"49 The fourth experimental model is
based on the manipulation of the muscle fiber's metabolism, for example, through the use of malnutrition paradigms.50, 51
All the experimental paradigms provide information that can be used for clinical practice. The relevance of studies examining the effects of use and
disuse is apparent. Less obvious is the need to understand the effects of drugs, such as corticosteroids,
which are commonly used for a variety of diseases.7, 52
Knowing that the steroid-treated patient has a selective type II atrophy means that exercises should be
performed that hypertrophy that fiber. Similarly, by
understanding metabolic studies, therapists can be
better prepared to treat the type II fiber area loss of
the cachectic cancer patient or of the malnourished
patient (eg, a patient with Crohn's disease).7 This
review will focus only on the changes in fibers seen
with varied patterns of disuse and increased use that
provide the basis for understanding all mutability
studies. Metabolic factors, drugs (including alcohol),
and the effects of aging are discussed elsewhere in
this issue.
REDUCED ACTIVITY AND DISUSE PARADIGMS
The most obvious changes that clinicians observe
resulting from disuse is loss of muscle mass. Classically, we have referred to this as atrophy, a nonspecific
term that describes the muscle as if it were a homogeneous entity. Experimentation on humans and animals has demonstrated that disuse atrophy is a complex phenomenon whose effects vary with fiber types
and with different muscles.
Experiments using immobilization of limbs provide
a nonsurgical disuse model that is analagous to what
is seen in orthopedic patients who have been immobilized in casts. By understanding the results of these
experiments, we can be better equipped to manage
patients with atrophy brought about by cast immobilization.
Cast Immobilization
Cast immobilization of normal animal muscle results in preferential atrophy of slow-twitch fibers.
Volume 62 / Number 12, December 1982
These fibers decrease in size and lose some of their
capacity for oxidative metabolism.44 Cast immobilization results in a decreased rate of protein synthesis
in all muscle fibers, with type I fibers showing the
greatest decrease.44,53 A physiological change also
takes place in the type Ifibers:they increase their rate
of tension development after having been immobilized.44, 54 The change in the contraction speed of
immobilized slow-twitch muscle fibers is unique.
There is no other known stimulus likely to occur in
normal animal muscle that leads to a change in
contraction time.1 In addition to the changes that take
place within the slow-twitch fibers, there is evidence
that in the soleus muscle (a predominantly slowtwitch muscle) of the rat and the guinea pig a loss in
the number of slow-twitch fibers occurs.55, 56 This loss
could explain the overall increase in contraction times
for those muscles. However, there is currently a controversy over whether slow-twitch fibers preferentially degenerate, or whether the loss in number of
slow-twitch fibers is a result of some being converted
to fast-twitch fibers.44
Although fiber-specific changes after immobilization have been repeatedly examined in animal muscle, only a few studies have been done with humans.
And as might be expected, the results from human
studies present a less cohesive picture than the one
presented in animal studies.
Sargeant et al studied seven patients whose lower
extremities had been in casts for an average of 131
days (range, 53-213).57 All patients had unilateral
fractures. Needle biopsy specimens were obtained
bilaterally from the lateral part of the quadriceps
femoris muscle. Fiber type distribution and area were
calculated for 50 to 100 fibers. When the muscle that
had been in the cast was compared with the muscle
of the uninvolved lower extremity, it was found that
1. There was no change in the numbers of type I and
type II fibers.
2. Type I fibers showed a greater atrophy (loss of
area) than the type II fibers in six of the seven
patients. The average type I loss was 46 percent,
and the average type II loss was 37 percent.
3. Overall, there was a 42 percent decrease in mean
fiber area.
These results support the following conclusions: there
was no fiber type conversion (eg, type I fibers did not
become type II), and there appears to have been no
selective degeneration (eg, loss of a specific fiber
type). In addition, this study extended to humans the
finding of preferential type I fiber atrophy as found
with cast immobilization.
Although cast immobilization allows for the investigation of muscle changes in humans, there is a major
problem associated with this method when the uninvolved limb is used as a control for the comparison of
1777
fiber area and frequency: use of this limb is likely to
increase during the period of cast immobilization.
Therefore, in this study it was possible that while one
limb was undergoing disuse, the other limb may have
been changing because of increased use. This increased use, as might occur with crutch walking, could
have led to compensatory hypertrophy (increase in
cross-sectional area) of the type II fibers. It should be
remembered that subjects in this study were immobilized in the casts for long periods of time (53-213
days).
Recently Haggmark et al reported on the effects of
casts applied to another population sample: eight men
and one woman from 25 to 40 years of age who
underwent surgical reconstruction of the anterior cruciate ligament (a modified Jones procedure).58 At the
time of surgery, biopsy specimens were taken from
the vastus lateralis muscles of both the involved and
uninvolved legs. The legs were then immobilized for
five weeks. During the time of cast immobilization all
subjects performed isometric excercises of the involved extremity. These consisted of contractions lasting three to six seconds, followed by rest periods of
six seconds. Initially, patients had difficulty doing
these exercises because of pain; however, Haggmark
et al reported that after a couple of days subjects were
able to "retrieve" their muscle function. The subjects
progressed to the point of doing the excercises for one
hour. Also, during the time they were in the cast,
subjects were allowed to use the limb for ambulation
within pain tolerances.
After removal of the casts another biopsy was
taken. Also, preoperative and postoperative measurements of thigh circumference were compared, and a
decrease in circumference was evident. Histochemical
analysis showed that there was a loss of area only in
the type I fibers when preoperative and postoperative
values were compared. Biochemical analysis of single
fibers demonstrated a loss of succinic dehydrogenase
(SDH, an oxidative enzyme) activity in the type I
fibers. There were no changes in the area or in the
metabolic activity of the type II fibers of the operated
limb or in either fibers of the uninvolved limb. The
type I fiber atrophy, which involved both fiber size
and loss of metabolic capacity, occurred despite the
use of isometric exercises. Although it is impossible
to say whether the exercises lessened the degree of
atrophy, the results demonstrate that isometrics did
not prevent atrophy in these patients.
The type I atrophy demonstrated by Haggmark et
al with patients who had undergone knee surgery is
in contrast to the mixed atrophy demonstrated by
Sargeant et al with patients with fractures. Several
explanations may be offered for the apparent discrepancy. One factor may have been methodological. As
was noted previously, Sargeant et al used the uninvolved limb as a control for comparison values.
1778
Haggmark et al used the preoperative values as a
control, and therefore the results could not have been
affected by changes in the uninvolved limb that might
have occurred with altered patterns of use. Also,
Haggmark et al's subjects were in casts for a much
shorter period of time but probably had more pain
than Sargeant et al's. Gydikov suggested that pain
has a greater inhibitory effect on the motoneurons of
the type I fibers than on the motoneurons of the type
II fibers.59 The type I atrophy Haggmark observed
may have been caused by pain rather than immobilization.
There remains a controversy over the type of atrophy seen in patients after cast immobilization. Muscle
pathologists have observed type II atrophy after cast
immobilization, unless the patient was in severe pain
(personal communication from M.H. Brooke, July
1982). This observation may strengthen the argument
that Haggmark et al's findings were related to the
effects of pain rather than of the cast. However, the
observation cannot explain the mixed atrophy reported by Sargeant et al. At the present time, clinicians might want to assume that a mixed atrophy
exists in cast-immobilized patients and plan their
exercises accordingly. Rehabilitation of the cast-immobilized patient apparently must include exercises
that improve endurance as well as strength. The need
for exercises that combine strength and endurance
training is reinforced by the results of a series of
experiments that combined training with cast immobilization in human volunteers.60, 61
MacDougall et al examined muscle metabolite concentrations in nine men who had trained and had
been immobilized in a cast.60 Biopsy samples from
the long head of the triceps brachii muscle were taken
from subjects who had their forearms immobilized in
casts for five weeks. Subjects were divided into two
groups. One group trained before cast immobilization
and the other after. A biopsy was taken from each
subject at the initiation of the study, after the casts
were removed, and after training. Metabolites measured were adenosine triphosphate (ATP), adenosine
diphosphate (ADP), creatine (C), creatine phosphate
(CP), and glycogen. Immobilization significantly reduced CP concentrations by 25 percent and glycogen
concentrations by 40 percent. Muscle homogenates
were used for biochemical analysis, and as a result,
fibers could not be identified where the metabolites
were lost. Of clinical interest was the interaction
between training and immobilization; subjects who
had trained before immobilization showed a greater
loss of metabolites; however, the group that trained
after immobilization demonstrated a greater increase
in metabolite concentrations as a result of training.
MacDougall et al's findings suggest that cast immobilization may in some ways be more deleterious
to the well-trained athlete than to the sedentary inPHYSICAL THERAPY
dividual. For the athlete, immobilization possibly
results in greater disuse and therefore leads to even
greater relative loss of muscle metabolic properties.
Conversely, the increased training effect seen in subjects who exercised after immobilization indicates
that for these subjects, exercise represented even
greater relative use. The results reported by MacDougall et al suggest that on a relative basis, deconditioned subjects may respond better to postimmobilization rehabilitation programs than do well-trained
athletes. It would appear that athletes need special
consideration following immobilization in order to
attain their previous high level of performance. Although the most obvious treatment would be to exercise with very high loads, this strategy would not
deal with the loss of endurance capacity found in
immobilized human muscle. However, it should be
noted that both of the metabolites found by MacDougall et al to be diminished, CP and glycogen, are
associated with the production of ATP during the
early phases of forceful muscle contractions. Concentrations of these metabolites are known to increase as
a result of high-power exercise.60
In a follow-up study, MacDougall and associates
used the same experimental design of taking biopsies
before and after sequential immobilization and training of the triceps brachii muscle.61 In this follow-up
study, histochemical staining was used to type fibers
and to examine the changes in fiber area and frequency. The group that trained before immobilization
consisted of four men, and the group that exercised
after cast removal consisted of three men. Subjects
were in casts for five weeks. Immobilization led to a
decrease in the areas of both major fiber types: type
I fibers decreased 25 percent and type II fibers decreased 33 percent. This decrease in type II fiber area
did not appear to be dependent on when the subject
had trained. Fiber area was similarly reduced in the
group that trained before immobilization and in the
group that was to begin exercise after immobilization.
This finding indicates that cast immobilization, relative to fiber area, causes similar atrophy in trained
and untrained muscle.
The results of this experiment on the triceps brachii
muscle are different from the results Sargeant et al
and Haggmark et al reported on the quadriceps femoris muscle. They found a preferential type I fiber
atrophy, similar to that found in animal studies.
Although MacDougall and associates reported a
mixed atrophy, the type II fibers actually showed a
greater loss in area.61 Further research will be required
to determine whether the apparent discrepancy between these studies is due to inherent differences in
the muscles, duration of immobilization, presence of
pain, or experimental methods.
A critical observation also may be made relative to
what appear to be inconsistencies in the two studies
Volume 62 / Number 12, December 1982
of MacDougall. In the first experiment, decrease in
metabolic substrate was dependent on prior training.
In the second study, decrease in cross-sectional area
of the type II fibers was not dependent on prior
training. Cast immobilization had a more deleterious
effect on metabolite concentrations in trained muscle
than in untrained muscle, whereas it had the same
effect on the cross-sectional area of trained and untrained muscle. These findings illustrate the complex
nature of atrophy and the need to define and to
understand the term in clinical practice. Subjects with
trained muscle seem to be more susceptible to one
effect of cast immobilization, specifically loss of ATP
precursors; they are not more susceptible to the loss
of fiber area. Therefore, clinical evaluation of the
cast-immobilized patient should include assessment
of prior training and activity levels.
Joint Dysfunction and Tendon Rupture
Cast immobilization is one situation in which muscle use is significantly reduced. Other clinical conditions in which inactivity leads to significant changes
involve joint dysfunction and tendon ruptures.
Edstrom described preferential atrophy of type I
fibers in the vastus medialis muscle of patients with
long-standing anterior cruciate ligament injuries.62
Biopsy specimens were taken from 10 subjects (9 of
whom were athletes) at the time of arthrotomy. He
reported that of the 4 subjects with the most pronounced signs of atrophy, 3 exhibited the greatest
degree of joint dysfunction and appeared to have the
most disability.
The changes that take place in the muscle of patients with osteoarthritis of the hip have been described by Sirca and Susec-Michieli.38 In younger
patients with osteoarthritis (37-64 years of age), they
reported a decrease in the percentage of type II fibers
in the gluteus medius, gluteus maximus, and tensor
fasciae latae muscles. In older patients with osteoarthritis (65-78 years) a decreased percentage of type II
fiber was found only in the gluteus medius and the
tensor fasciae latae muscles. In the older group, the
percentages in the gluteus maximus muscle did not
differ from age-matched autopsy controls. In the
younger group, there was a decreased fiber diameter
for both type I and type II fibers in the gluteus medius
and the tensor fasciae latae muscles. The diameter of
type II fibers decreased in the gluteus maximus muscle, whereas the diameter of the type I fibers was
similar to that of the controls. The pattern of atrophy
in the gluteus maximus muscle clearly differs between
the two age groups, but the significance of this finding
has yet to be investigated.
The findings of Sirca and Susec-Michieli cannot be
explained on the basis of aging because each of their
groups was compared with age-matched autopsy con1779
trols. It is clear, however, that the mixed pattern of
muscle atrophy in patients with osteoarthritis differs
from that seen in patients with cast immobilization
and ligamentous injuries of the knee. It has not been
determined whether this difference is caused by some
factor associated with the disease process, such as loss
of motion or pain, or is representatve of a unique
activity pattern, or is caused by some other factor.
Following rupture of the bicipital tendon, Jozsa et
al found that there was a reduction in the area of type
I fibers and a decrease in the percentage of type I
fibers in the long head of the biceps brachii muscle.63
The area of the type II fibers remained the same.
Comparisons of nine subjects were based on biopsy
samples from the uninvolved arm. Because the time
from tendon rupture to biopsy and repair varied from
one day to six months, it was difficult to assess the
rate of atrophy in these patients. However, it appeared
that fiber area changed similarly in all patients,
whereas fiber number appeared to depend on length
of time since tendon rupture.
INCREASED ACTIVITY AND USE PARADIGMS
Disuse has been shown to cause changes in almost
all muscle characteristics. Similarly, increased use of
muscle also leads to a wide variety of changes. The
most obvious method for increasing use is the lifting
of heavy loads for a relatively low number of repetitions (strength training). This exercise usually results
in an increased muscle mass and is probably the only
paradigm for increased use that produces muscle
hypertrophy.64 This paradigm may be contrasted to
situations where the muscle works against a light load
for a relatively large number of repetitions. This latter
form of exercise has been called endurance training
and results primarily in altered metabolic characteristics within muscle fibers.65 Although, clinically, endurance training has been considered only from the
standpoint of load and repetitions, there is another
critical variable that affects the type of changes muscle undergoes. This variable is intensity, relative to
maximal oxygen uptake of the individual.66 When
high-intensity exercise is performed for a period of
time, the changes that take place in the muscle are
different from those seen with traditional strength
and endurance exercises.26, 67-69
Muscle responds to use in a wide variety of ways
that are dependent on the exact nature of the training
stimulus. To fully understand the effects of clinical
procedures, a conceptual framework that relates all
possible stimuli and responses must be developed.
Low Loads and High Repetitions
To investigate the response of muscle to low load
and high repetitions (increased frequency of use),
1780
Salmons and Henriksson4 developed just such a conceptual framework based on the transformation of
type II to type I fibers. They have suggested that
when an increased metabolic demand is placed on
muscle through endurance training or chronic electrical stimulation there is a "hierarchy of stability" of
muscle properties that can be demonstrated by systematically changing that functional demand. The
early changes seen with chronic electrical stimulation
of muscle are similar to those seen with endurance
exercises.4 Apparently, each mutable property of muscle has a different threshold of use that must be
reached before change can occur.70 The thresholds
for these various properties, such as metabolism and
contraction speed, fall along a continuum. There is a
consistent sequence of changes that occur in muscle
that is directly related to the type and duration of use.
Salmons and Henriksson reviewed a series of experiments with chronic electrical stimulation that demonstrated fiber transformation from fast twitch to
slow twitch.4 The documentation of the sequential
changes that occurred during these fiber transformations has given us a framework for explaining the
variety of results of experiments examining the effects
of increased muscle use.
Electrical Stimulation
Fiber transformation from type II to type I has
been accomplished in animals primarily through the
use of indwelling electrodes that delivered 10 Hz
pulses continuously to motor nerves for six weeks or
more.4 Contractions obtained in this way were palpable but not very forceful. By sacrificing animals at
intervals during this stimulation period, the changes
that occurred could be recorded. It was discovered
that at various stages of stimulation, the different
muscle properties were changing. For example, after
one week, changes in capillary density could be seen,
and after two weeks, changes in rate of tension development could be observed. The following is a
compilation of some of these changes from a variety
of experiments:4
Within one week: Increased capillary density was
observed as was an increased resistance to fatigue.
Cytological changes (eg, decreased T system) associated with type I fibers were found.
Within two weeks: Oxidative capacity increased
along with mitochondrial volume. Glycolytic enzymes were reduced. Cytological changes (eg, increased Z disk thickness) consistent with type I fiber
transformation were found. There was also a loss of
sarcoplasmic reticular proteins and decreased activity
of calcium uptake. At this point, the muscle also took
on the isometric contraction characteristics of the type
I fiber with increased time-to-peak tension and increased time-to-half relaxation.
PHYSICAL THERAPY
Within three weeks: Myosin ATPase activity was
reduced.
Three to eight weeks: Changes occurred in contractile and regulatory proteins consistent with fiber
transformation.
Eight weeks: The maximum velocity of shortening
under isotonic conditions was significantly reduced.
These experiments examined whole muscle, and it
was noted that after fiber transformation the whole
muscle may actually become even slower than normal
slow muscle. This may have happened because after
stimulation the muscle was completely slow-twitch,
whereas normal slow muscle, such as the soleus muscle, usually contains some fast-twitch fibers.4 Experiments in which electrical stimulation was discontinued showed that reversal of fiber transformation (return to fast twitch) takes place with the sequence of
events reversed. During the process of transformation
of type II to type I, there was no change in the
number of fibers in the muscle. However, the area of
the fibers decreased.
In this review we have reported that electrical
stimulation results in fiber transformation. Several
alternate hypotheses to explain these results have
been made. A complete listing of those and a discussion of why they may not be valid are presented by
Salmons and Henriksson.4
The electrical stimulation used in the studies described above was essentially low frequency and
chronic (continuous). To determine whether the critical factor was frequency or stimulus duration, Sreter
et al examined the effects of 60 Hz stimulation (for
five weeks) on the fast extensor tibialis anterior muscle of the rabbit.71 The results were similar to those
found with 10 Hz stimulation. Because the 60 Hz
stimulation resembled the discharge frequency of fast
motor units, the results suggest that the amount of
activity a muscle engages in, rather than the discharge
pattern, may be the critical stimulus for fiber transformation. Sreter et al, however, found one difference
when the higher frequency pattern was imposed on
muscle. Normally, muscle undergoing fiber transformation from 10 Hz stimulation loses between 30 and
50 percent of its mass compared with the nonstimulated leg. With 60 Hz stimulation, no change in mass
was found. This may imply that the muscle fiber type
is dependent on the degree of overall activity, whereas
muscle mass may be related to the pattern of use.
It should be noted that attempts to convert denervated slow muscle to fast muscle72'73 have not provided clear-cut results that can be used to understand
stimulus variables needed for this type of fiber transformation.
One study examined the effects of electrical stimulation on human muscle fibers. In an attempt to
reduce "refractory" knee flexion contractures, Munsat et al stimulated the femoral nerve with implanted
Volume 62 / Number 12, December 1982
electrodes in five patients.74 When phasic stimulation
(33 Hz every four hours for one hour; 5 seconds on,
25 seconds off) was performed on four patients with
fixed contractures of the knee, isometric contractions
resulted. In the fifth patient, a surgical release of the
rectus femoris muscle allowed the stimulation to produce a more isotonic contraction of the muscle because the muscle could shorten. In the four patients
with isometric contractions, the number of type I
fibers increased and both type I and type II fibers
increased in size. In the patient with a tenotomized
muscle, the number and size of type I fibers decreased.
The results of Munsat et al's study are intriguing
and suggest that electrical stimulation variables and
the type of muscle contraction (ie, isometric or isotonic) must both be considered determinants of fiber
transformation. However, their findings must be applied cautiously in view of the following limitations
of the study: 1) the isotonic condition in this study
also involved tenotomy, and as a result there was no
"true" isotonic contraction (there was no resistance);
2) the results are based on four subjects in one group
and one in another; 3) these patients may not have
had normal muscle at the beginning of the study as
a result of their longstanding contractures, because
these quadricep femoris muscles had undergone contracture-induced immobilization in a lengthened position (knee flexion).
The electrical stimulation experiments detail how
and when muscle changes. To apply this information
to the clinical setting, it is necessary to review some
of the experiments that deal with endurance training.
Endurance Training
In animals, repeated experimentation has shown
that with endurance training, such as long distance
running, the primary effects involve alteration of the
fibers' metabolic capacity.65 There is an increase in
the respiratory capacity of muscle (eg, increased mitochondrial volume); a rise in the ability to generate
ATP via oxidative phosphorylation by metabolizing
fats, carbohydrates, and ketones; an increase in
myoglobin content; and increased capillary density.
Therefore, the changes that take place with endurance
training are similar to those that occur during the
early phases of chronic electrical stimulation. The
only difference in effect between endurance training
and chronic electrical stimulation is that endurance
training apparently cannot significantly change muscle contraction characteristics.4 With chronic electrical stimulation, muscle is in constant use, whereas
during even the most rigorous endurance programs,
muscle is only intermittently active. Contractile characteristics, such as speed of contraction, have been
1781
shown to be among the last properties of muscle to endurance capacity of the high-tension developing
transform during electrical stimulation. Although en- type II fibers.
This finding has implications for rehabilitation.
durance training is a potent stimulus for muscular
changes, it appears that it cannot be carried out for Patients who will be required to function at relatively
long enough periods of time to lead to changes in low work loads, with relatively low tension developmuscle contraction characteristics or to alter the re- ment, can be trained at low intensities. However, if a
lated properties of myosin ATPase. Chronic electrical patient needs to function for prolonged periods of
stimulation brings about total change in muscle char- time at high work loads, with possibly high levels of
acteristics because it is a stimulus that leads to the tension required, they must undergo high-intensity
highest level in the hierarchy of change; endurance endurance training. The extension of the findings on
endurance training to patients is at present our hytraining does not reach that level.4, 70
Human muscle appears to respond to endurance pothesis and has not yet been proven valid by clinical
training in much the same way as animal muscle, that research.
is, with increases in oxidative capacity.26, 31, 65, 75-77
Conversion of the various subtypes of type II fibers
However, this increase in oxidative capacity occurs in has been shown by Andersen and Henriksson.68 With
different muscle cells, depending on the intensity of submaximal exercise (30 minutes, four days a week
the exercises relative to maximal oxygen uptake for eight weeks at 81% Vo 2 max ), type IIB fibers were
(Vo2max). Gollnick et al found that when subjects converted into type IIA fibers. Because the type IIA
exercised intensely (from 75-90% Vo 2 max ) one hour fibers have a greater oxidative capacity, this result
a day, four days a week for five months, histochemical may have been expected. A more controversial findstaining showed an increase in oxidative capacity in ing was reported by Jansson et al, who contend that
both type I and type II fibers of the vastus lateralis with appropriate training there can be interconversion
muscle.75
of type IIC and type I fibers.69
Jansson et al reported that some type I fibers
Henriksson and Reitman used biochemical analysis
to examine the training effect when intensity was convert to type IIC fibers during "anaerobic training"
varied.67 This method is a more sensitive means of (running at 90-100% Vo 2 max two or three times a
assessing enzyme changes than the histochemical week for a total of 44 miles). They also reported that
method used by Gollnick et al. Henriksson and Reit- with "aerobic training" (running at 70-80% Vo2 max
man showed that when subjects exercised at about 80 for a total of 68.2 miles a week) conversion in the
percent Vo 2 max for 27 minutes a day, three days a opposite direction took place: type IIC fibers became
week for eight weeks, there was a significant increase type I fibers. This report is the only one in the
in SDH activity of the type I fibers of the vastus literature to make the suggestion that training can
lateralis muscle. Another group of subjects trained at convert type II fibers to type I fibers. Fiber conversion
about 92 percent Vo 2 max for three days a week with through training is a controversial suggestion, and
five work periods separated by two minutes of rest. one must take into account that the level of training
These subjects, who exercised at an intensity that for Jansson et al's anaerobic paradigm was extraorapproached their maximum capacity, showed an in- dinarily intense. Most endurance training appears
crease in SDH activity in only the type II fibers. With incapable of producing the threshold needed to convery high intensity endurance training, only the oxi- vert type II fibers to type I fibers.
dative capacity of the type II fibers increased. With
Another endurance study suggested that the type
low intensity exercise, oxidative capacity increased IIC fiber is really an intermediate form between the
only in the type I fibers. In both the high and low type I and type II and that the IIC is a fast, endurant
intensity groups, there was no change in phospho- fiber.25 Ingjer used an interval training approach: the
fructokinase activity. The stability of this glycolytic subjects ran 45 minutes three days a week, one day at
enzyme indicates that in neither group was there an 50 to 90 percent Vo 2 max and the other two days
increased capacity for anaerobic metabolism.
intermittently at 100 percent Vo 2 max for 24 weeks.25
Increased oxidative capacity is the result of endur- (Not surprisingly, only seven of the original 15 subance training and occurs in the type I fiber when the jects completed the study.) After training, there was
intensity of work is low and in the type II fiber when an increase in the percentage of type IIA fibers and
the intensity is high. Therefore, endurance training is a decrease in the percentage of type IIB fibers, sugnot a single form of exercise and certainly does not gesting a conversion between the two types. Ingjer
lead to similar changes in all muscle. Response to proposed that this took place via a type IIAB fiber
78
endurance training is dependent on the level of work that was previously described by Gronnererod et al.
and effort during the training. Low-level endurance These IIAB fibers, which are not included in most
training will increase the oxidative capacity and, classification schemes, have a size, capillary supply,
therefore, endurance of the low-tension developing and mitochondrial content intermediate between type
type I fibers. High-intensity work will increase the IIA and type IIB fibers. Another finding of Ingjer's
1782
PHYSICAL THERAPY
was that the type IIC fiber, which is relatively uncommon, increased in number from 0.4 percent to 2.29
percent after training. Because this type IIC fiber
resembled the type I fiber cytologically and enzymatically, Ingjer argued that the IIC may be derived from
the type I fiber.
In every circumstance, endurance training improves the oxidative capacity of muscle. When intensity is low, this improvement is restricted to the type
I fiber. When intensity is high, the improvement
occurs in the type II fiber and probably is accompanied by conversion of the type IIB fiber into a type
IIA fiber. The possibility exists that type IIC fibers
may be converted under extreme training conditions
into type I fibers. Because the only evidence for
conversion through training comes from a paradigm
with high intensity, the hierarchical model of Salmons
and Henriksson may be applicable.4 This model states
that changes take place along a continuum and that
as stimulus intensity and duration increase, the
changes that take place in a muscle increase. Total
fiber conversion may be possible only under the most
extreme circumstances. It must be emphasized, however, that this hierarchical model was based on animal
experimentation. If the same type of process with
similar time courses is shown to exist in humans, then
exercise programs may be developed that could vary
specific muscle properties by working up to the desired level in a hierarchy.
Muscle Use and Development
Muscle mutability demonstrated through electrical
stimulation and endurance experiments has provoked
some questions about how muscle development may
be affected by patterns of muscle use. According to
Salmons and Henriksson, there is in the fetus a unique
form of myosin, the most abundant muscle protein,
whereas the other muscle proteins are biochemically
similar to those seen in adult fast-twitch muscle.4 At
birth, or shortly thereafter, type I fibers appear. The
number of type I fibers at birth varies greatly between
species and is apparently dependent on how mature
the organism is at the time of birth. According to
Salmons and Henriksson, development of type I fibers proceeds postnatally in a fashion that is
"reminiscent of the changes evoked in adult fast
twitch muscle by chronic low frequency stimulation,
suggesting that the emergence of slow-fiber properties
in the course of ontogenetic development could be
contingent on the establishment of definitive patterns
of motor activity in the maturing nervous
system."4(p101) This would suggest that developmental
approaches to patient care that have focused primarily on the nervous system79 may have been promoting
normal ontogenetic development of the highly mutable maturing muscle. This hypothesis, which would
Volume 62 / Number 12, December 1982
offer new scientific foundations for some physical
therapy treatment strategies, needs to be investigated
further. The possibility that developmental intervention may be a stimulus for normal development in
the periphery, namely in the muscle, is a provocative
concept.
Strength Training
All of the preceding discussion relating to increased
use is based on two conditions: either the intensity
relative to V0 2 max was varied, or the subjects worked
against low loads for many repetitions. Both of these
conditions relate to the concept of endurance. The
next important type of use paradigm deals with maximal efforts, something traditionally referred to as
"strength training." Generalization of the results of
strength training studies is difficult because the term
strength, as applied to exercise, has no single meaning.
Strength is usually operationally defined in each
study.
What makes interpretation of strength training literature even more difficult is the use of what therapists might consider nonspecific forms of exercise.
For example, one group examined changes in the
fiber composition of the vastus lateralis muscle after
subjects exercised by doing squats,34'64 an exercise
that involves not only the knee extensor muscles but
much of the hip musculature. Further confusion has
been created by studies in which strength training
consisted of multiple exercises that may or may not
have been accomplishing the same goal.60, 80
Despite the multiple sources of confusion that seem
to dominate the strength training literature, the following general observations can be made: 1) type II
fiber area increases in response to heavy resistance
training61; 2) type II fiber area appears to correlate
with the maximal isometric strength81-84; 3) there is
no definitive picture as to the changes that take place
in the fiber's metabolic capacity1, 60, 85; and 4) myofibrillar proteins increase, resulting in enlarged or hypertrophic muscle fibers.1, 9, 10 Beyond these generalizations, it is difficult to discuss strength training
because of the problems listed above. The readers are
urged to examine the following references for a view
of some of the strength training literature: MacDougall et al,60, 61, 80 Thorstensson,64 Nordemar et al,81
Grimby et al,82 Costill et al,85 Komi et al,86 and
Thorstensson et al.87
The effects of strength training described above are
generally agreed upon. However, there is an additional effect that has been infrequently observed and
is highly controversial—fiber splitting. Advocates of
fiber splitting as an effect of strength training believe
that when a muscle cell hypertrophies, it reaches a
maximum size and, therefore, further hypertrophy is
impossible. They suggest that additional strength
1783
gains can only be made through the addition of fibers,
which occurs when existing fibers (cells) divide and
split. Gonyea and associates in different studies have
been the primary advocates of thefibersplitting effect
and have reported seeing the phenomenon in exercised cat muscle.88-90 Those who believe in fiber splitting remain a minority in the field of muscle biology.
Experiments demonstrating fiber splitting have yet to
be replicated. One of the major reasons why fiber
splitting has not been conclusively demonstrated in
response to training is the possibility that fiber splitting is not really biological but rather an artifact of
the way muscle is prepared for morphological analysis. The studies that have reported fiber splitting in
response to training have been done in animals. Fiber
splitting is also known to occur in human muscle but
has always been associated with a dystrophic process
or some other disease.91
One group reported the effects of strength training
programs on postoperative orthopedic patients.
Grimby et al used three different kinds of training
programs on 30 patients who had surgery for tears of
the anterior cruciate or medial collateral ligaments,
or both.82 Subjects were athletes with a mean age of
26 years (range of 16-46 years) who had been operated on approximately 14 months before the beginning of this study. All the subjects received postoperative physical therapy consisting of quadriceps femoris and hamstring muscle training once a week for
two to three months, and the therapy was supplemented by a home program. At the time they began
the training study, all had returned to athletic competition and could fully extend and flex their knees
to at least 100 degrees without pain. Two of the three
training groups performed what might be considered
strength training exercises. One group trained isokinetically, extending the knee 10 times from a position
of 100 degrees of flexion at a speed of 42°/sec. Three
sets of 10 contractions were performed with a oneminute rest between contractions. This was done three
days a week for six weeks. The second group used a
quadriceps table where a weight was set so as to exert
maximum resistance at 60 degrees from full extension.
Subjects then exercised using the maximum weight
that they could lift 10 times. This was repeated three
times with a one-minute rest between bouts. This
group also trained three days a week for six weeks.
Both groups warmed up for five minutes on a bicycle
ergometer before the training exercises.
The isometric strength of the operated limb was
approximately 80 to 90 percent of that of the nonoperated side before training. Both groups increased
their strength when measured isometrically or isokinetically at speeds of 30 and 42°/sec, and the isokinetic group also improved at 120°/sec. However, it is
interesting to note that when the increase in force
values were examined, the isokinetic group improved
1784
more isometrically than did the other group but
showed equal improvement isokinetically.
Muscle biopsies taken before and after training
showed no significant change in fiber areas despite
the observed changes in the various strength measures. There was also no significant change in the
concentrations of CP, ATP, lactate dehydrogenase,
and myokinase. The results of this study demonstrate
that in well-trained individuals, strength training may
lead to increases in performance measures, such as
force and torque, without changes being observed in
the area or the metabolic profiles of muscle fibers.
Methodological suggestions. The contrast is sharp
between the systematic approach to endurance training and the multiple methods of examining strength
training. Investigators examining the effects of endurance training almost always use a bicycle ergometer and examine effort or intensity in terms of
V02 max. By using a common method and by sharing
a commonly defined variable, studies may be related
to each other and findings generalized.
As was noted earlier, strength lacks a single definition and must be operationally defined. Perhaps
systematization of future studies will be aided if the
term "strength" is replaced by the term "power"
which can be readily defined (Power=Work/time).
Because this term is defined in classical physics, it can
be measured and reliably used by others. Just as
endurance studies report the level of effort in terms
of V02 max, so might future studies on maximal efforts
report their procedures in terms of the percentage of
maximal power production a muscle may achieve.
For power to be used as a replacement for strength in
clinical settings, therapists will need to modify some
of their methods of measurement. This modification
appears to be both feasible and useful.92, 93
SUMMARY
We have selectively examined the literature on
muscle mutability in response to altered patterns of
use. The body of literature is vast and is increasing
everyday as new reports are published. We believe it
is essential for physical therapists to meet the challenge of keeping current with this literature and of
extrapolating clinically useful information.
Throughout this article, we have attempted to review clinically relevant observations when we thought
them appropriate. At times, we have engaged in
conjecture, some of which undoubtedly will be refuted. Many points have been made in very general
terms because the clinical application is unknown.
For example, it was argued that under certain circumstances intensity or repetitions should be increased to
cause a desired effect. However, knowing that physiologists increased the aerobic capacity of type II
fibers in athletes by training them at greater than 90
PHYSICAL THERAPY
percent of their Vo 2 max does not tell us what training
level would be required for a sedentary middle-aged
person or an elderly patient.
The challenge that now faces physical therapists is
to use the literature on muscle mutability to generate
meaningful clinical hypotheses and to test them.
These hypotheses could give rise to new treatment
strategies that could be examined for efficacy through
clinical investigations. Only through the testing of
ideas on patients in a clinical setting can we define in
clinical terms the types of procedures that will lead to
desired changes in muscle.
The research effort that will be needed before we
can optimally apply the concepts of muscle biology
to patient care may seem immense. However, we
believe that the benefits of such an effort will make
the cost worthwhile. The potential value of using
muscle biology for patient care was first described by
Engel, one of the pioneers in the field. He wrote:
To learn the mechanism of type II fiber
atrophy would be of general impor-
tance—many patients with cancer and
other chronic diseases appear to be more
incapacitated by the generalized weakness of type II fiber atrophy than by any
other aspect of their disease. If a method
of reversing or preventing type II fiber
atrophy could be found, many such patients could be greatly benefited even
if their basic disease remained untreated.7(p113)
The evidence reported in this review supports our
contention that muscle is among the most mutable
tissues in all of biology. It is also apparent that this
mutability can have beneficial as well as negative
effects on human functioning. Muscle appears to be
dynamically changing from moment to moment in
response to the patterns of use imposed upon it. It is
likely that our success or failure with our patients will
frequently depend on our ability to understand and
use this dynamic capacity.
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