Injury to skeletal muscle fibers during contractions: conditions of occurrence and prevention.

Injury to skeletal muscle fibers may occur as a result of sharp or blunt trauma; excessively hot or cold temperatures; myotoxic agents, such as bupivacaine hydrochloride or lidocaine; ischemia; muscle diseases, such as dystrophy; inflammation; and the contractions of the muscles.[1] In each case, the injury results in necrosis of some, or all, of the fibers in a given muscle. Within an injured fiber, the injury may be focal and involve only a few sarcomeres in series or in parallel, or it may involve all of the sarcomeres.[2] In the latter case, the whole fiber becomes necrotic. The processes of fiber degeneration and regeneration appear to follow a common pathway regardless of the factor(s) responsible for the injury to the muscle fibers.[1] This review will deal only with the factors associated with the occurrence of injuries to skeletal muscle fibers caused by their own contractions (contraction-induced injuries) and the types of training programs that prevent such injuries. Muscle contractions likely cause small, insignificant injuries to muscle fibers daily, but more severe, less frequent injuries accompanied by delayed-onset muscle soreness are also possible. Armstrong[3] and Stauber[4] have written earlier reviews on contraction-induced injury.

Hough[5] Was the first to describe the phenomenon of delayed-onset muscle soreness. When subjects performed rhythmical contractions of the finger flexor muscles until fatigued, Hough noted that the muscles became sore. The soreness was not reported at the time of the contractions, but developed 8 to 10 hours later and was most severe 48 to 60 hours afterward. Muscles trained to perform the rhythmical contractions did not demonstrate soreness. During the past decade, an extensive volume of literature has accumulated on the subject of delayed-onset muscle soreness.[2,6-12] These studies established that, for human beings, the delayed soreness in exercised skeletal muscles was more likely to occur and to be more severe after exercise consisting of predominantly lengthening (eccentric) contractions than after exercise consisting of either isometric or shortening concentric) contractions.[7,11] Furthermore, the soreness was associated with swelling[12]; an enzyme efflux, particularly creatine kinase release[7,13]; increased ratio of oxidized to reduced glutathione[14]; histological[9] and electron microscopic[6] evidence of injury to muscle fibers; and a decreased development of muscle force.[5,12,15]

The muscle tissues from human beings were obtained by needle biopsy technique,[6,8,9] whereas data on mice and rats were obtained from whole skeletal musdes.[14,16-19] The muscle biopsies and blood samples from human beings present similar direct and indirect evidence of injury compared with that obtained on whole muscles from mice and rats exposed to comparable types and intensities of exercise.[2,6,9] The similarity of the type and magnitude of the injury to muscle fibers and to their ultrastructural elements in the two data sets supports the premise that the biopsy sampling of large muscles in human beings does not bias the data significantly.

Total organism exercise protocols for mice, rats, and human beings have been developed that produce postexercise evidence of injury to the ultrastructure of skeletal muscle fibers in specific muscle groups.[2,6,8,9,20] In Spite of the success in producing injury, the muscle groups are complex, the volitional recruitment patterns produce variations in the proportions of quiescent and contracting motor units in any given muscle, and the actual metabolic or mechanical strains placed on individual muscle fibers are unknown. In addition, even for the contracting fibers, the complex, voluntary movements preclude any realistic assessment of the loading, the velocity of shortening or lengthening, and the magnitude of the displacements of muscle fibers.[21,22] Consequently, determinations of cause-and-effect relationships regarding the underlying mechanisms are not possible.

Investigations of isometric contractions of isolated whole skeletal muscles studied in vitro in a muscle bath have clarified the factors involved in the enzyme efflux from damaged muscle fibers.[23] The primary factors include the influx of calcium into the muscle[24] and calcium-mediated activation of phospholipase A.[25] Protocols of isometric contractions that cause severe injury in vitro[23] cause no injury when muscles are studied within the animal.26 Furthermore, the muscle membrane appears to be damaged more easily, and to a greater degree when muscles are in vitro[23-25] compared with in situ.[26] In spite of these differences, the in vitro model of contraction-induced injury has provided important insights.

The remainder of the review will focus primarily on data obtained from two mouse models of contraction-induced injury: the extensor digitorum longus (EDL) muscle in situ[26] and the dorsiflexor muscle group in vivo.[27,28] These models have the advantage of control of the load, velocity of shortening or lengthening, and magnitude of displacement.[26] In addition, the muscles may be excised for determination of the fiber lengths; muscle architecture; and the extent of the structural and functional injury by morphological, biochemical, and physiological techniques.[26,29,30]

Types of Contractions

When skeletal muscle fibers are activated and contract, three different types of contractions may result (Fig. 1). If the force developed by the muscle is greater than the load on the muscle, a shortening (concentric) contraction occurs. When the force developed by the muscle and the load are equivalent, or the load is immovable, a fixed length, or isometric contraction, results. The third type of contraction occurs when the load on the muscle is greater than the force developed by the muscle and the muscle is stretched, producing a lengthening (eccentric) contraction. Because muscles may shorten, remain at the same length, or lengthen during a contraction, a contraction is defined in muscle physiology as activation of muscle fibers with subsequent strong binding and cycling of crossbridges and an attempt of sarcomeres to shorten.

Any movement by an animal involves contractions during which fibers in different muscles shorten, remain isometric, or are lengthened.[22,31] Controlled movements require co-contractions of agonistic muscles, which shorten, and antagonistic muscles, which lengthen. In contrast, ballistic movements at high velocity require braking by antagonistic muscles that are stretched.[32] The terms "concentric exercise" and "eccentric exercise" have been used widely to describe movements that are perceived to be composed predominantly of shortening and lengthening contractions, respectively. The terms are ambiguous and have no inherent meaning. With the acceptance of the definition of contraction as an attempt to shorten, the apparent redundancy of the term "shortening contraction" and incongruity of the term "lengthening contraction" are resolved. Consequently, although not completely satisfactory, we believe these terms appear to be the most useful and understandable, and will be used throughout this review.

Contraction-induced Injury to Muscle Fibers

Injury to skeletal muscle fibers may occur during shortening, isometric, or lengthening contractions.[8,15,18,23,26] In spite of the potential for injury during any type of contraction, the probability of injury is greatest during lengthening contractions.[26] The increase in the probability and severity of the injury during lengthening contractions is so great[26] that injury is more prevalent even during total, whole-body activities that have a predominance of lengthening contractions.[11,13,15] Contraction-induced injury is also reported after competitive marathon runs,[33] apparently when unfatigued, untrained muscle fibers are recruited.[34]

Criteria of Injury

Direct evidence that a particular protocol of contractions has produced injury requires either histological[9,20,26] or electron microscopic[2,6,8] sections that show significant injury to a significant number of muscle fibers. Direct evidence is the ultimate criterion of contraction-induced injury. This creates some problems in evaluation of injury immediately after a protocol of contractions. Light microscopy of histological sections of muscles demonstrates significant cellular damage 2 days or more after the initial injury Fig. 2), but not at earlier time periods.[26] Such histological sections include those fixed in Bouin's solution, or frozen and stained with hematoxylin and eosin (H and E),[26] and those embedded in Spurr low-viscosity embedding media and stained with toluidine blue.[29] minor injury to fibers immediately after downhill running demonstrated with high-power light microscopy cannot be attributed to "the eccentric exercise" that preceded the identification of the injury.[16] The control experiments and sampling were not adequate to attribute these minor injuries specifically to the exercise that immediately preceded the identification of the injury. Furthermore, downhill running likely involves all three types of contractions, even for a specified muscle group.[22,31] The only direct evidence of injury immediately after contractions is the presence of ultrastructural damage demonstrated by electron microscopy.[2,8] Damage to individual fibers demonstrated by electron microscopy (Fig. 3) is visible for several weeks after the contractions.

The highly focal nature of contraction-induced injury to specific sarcomeres in individual fibers presents major sampling difficulties for quantitative evaluations of the magnitude of the damage as well as for determination of the immediate cause of injury. A quantitative evaluation of electron micrographs is not feasible, and only two studies[20,26] have attempted quantitative assessments with light microscopic techniques of the direct injury 3 days after the initial injury. In a single cross section through the belly of the EDL muscle, McCully and Faulkner[26] reported a 35% loss in the number of fibers when the decrease in force was 50%. They attributed the 15% discrepancy between the loss in fiber cross-sectional area and the loss in force development to fibers that appeared intact in the sampled section but that were injured at other levels. Ogilvie and associates[20] did not measure force before or after the injury. Therefore, a comparison between direct injury to fibers and the loss in force was not possible. They did present direct evidence of extensive damage throughout the soleus muscle.

In any given study, direct measurements of damage to muscle fibers should be present to support indirect measures of muscle damage. The indirect measures include enzyme release from muscle fibers[7,15,18,23] increased calcium influx[24,25]; increased glutathione ratio[14]; in the absence of fatigue, a decrease in the development of relative maximum isometric tetanic force or relative maximum power[15,26]; and in human beings, the report of muscle soreness.[11,12,35,36] With the support of direct measures, indirect measures provide quantification of the magnitude of the injury.

After a given protocol of lengthening contractions, the enzyme efflux from muscle fibers is suggestive of damage to the plasmalemma of fibers. Enzyme release occurs within an hour after the injury when muscles are in vitro,[23] but is delayed several days when injured muscles are in vivo (Fig. 4A).[7,36] At any given time after an exercise protocol, the enzyme efflux, particularly as measured by the plasma creatine kinase concentration, is highly variable, with an almost tenfold difference between the subjects with the highest and lowest responses.[7,36] The reason for the high degree of variability in blood concentrations of creatine kinase is unknown.

Given the problems with quantifying structural damage to muscle fibers and the variability in plasma enzyme levels as indices of injury, we conclude that a decrease in the maximum force developed by a muscle[26] or muscle group,[12,28,36] although an indirect measure, provides the most valid measure of the totality of the injury (Fig. 4). In addition, for a given protocol of lengthening contractions, the decrease in the development of maximum force is highly reproducible, with little variability from animal to animal (Fig. 4B).

Sequence of Events

The increased probability of injury during lengthening contractions arises in part from the greater average forces developed by fully activated muscles during lengthening compared with shortening or isometric contractions (Fig. 1). The force developed during a lengthening contraction is approximately twofold greater than that developed during a maximum isometric tetanic contraction. The lowest forces are developed during shortening contractions. The total number of crossbridges attached in a strongly bound state during lengthening is only approximately 10% greater than the number attached during an isometric contraction.[37] Consequently, the increased force development during a lengthening contraction reflects an increased strain on individual crossbridges.

During a single lengthening contraction, the average force developed is linearly related (r=.73) to the magnitude of the stretch beyond the optimum length of fibers for force development ([L.sub.f]) (Zerba E, Faulkner JA;unpublished research). When muscles are exposed to a single stretch beyond 140% of [L.sub.f], direct morphological evidence of injury and a decrease in force are observed. The magnitude of the decrease in force is partially correlated with both the average force developed during the lengthening contraction and the displacement beyond [L.sub.f] (Zerba E, Faulkner JA; unpublished research). The product of average force and displacement is the work required to stretch the active muscle. The work done to stretch the active muscle explains 87% of the variation in the decrease in force.

During repeated lengthening contractions, the relationship between average force and displacement is lost due to average force declining rapidly as a result of fatigue.[30,34] Under these circumstances, the magnitude of the displacement, or strain, on the active muscle appears to be the primary factor inducing the injury,[38] but this is an artifact of the experimental design. McCully and Faulkner[26] have shown that muscles fatigued previously by isometric contractions are resistant to injury by a subsequent protocol of lengthening contractions.

In the mouse, both in situ[26] and in vivo[28] muscle preparations have been useful in characterizing the sequence of events following contraction-induced injury. The single EDL muscle in situ and the dorsiflexor muscle group in vivo have been subjected to similar protocols of lengthening contractions, and the sequence of events during the 30 days following each protocol is both qualitatively and quantitatively similar. Consequently, the changes in relative maximum force of the tibialis anterior (TBA) and EDL muscles from either the in vivo or the in situ model illustrate effectively the sequence of events associated with the onset of, and recovery from, contraction-induced injury.

Initial injury. Stretching a single passive fiber to longer lengths prior to an isometric contraction increases the heterogeneity in the lengths of individual sarcomeres.[39] Presumably, stretching an active fiber or whole muscle similarly increases the heterogeneity in sarcomere length. Furthermore, Higuchi et al[40] have shown that repeated stretching of passive fibers beyond overlap of thick and thin filaments results in injury to the myofilament structure. Similarly, by electron micrographs, Brown and Hill[41] have demonstrated disruption of sarcomeres after single stretches of activated muscle fibers (Fig. 5). Our working hypothesis is that, during lengthening contractions, some sarcomeres maintain their length, whereas other sarcomeres are stretched beyond overlap and are injured. Consequently, the initial injury is predominantly mechanical injury to individual sarcomeres. The initial injury is greater under conditions of high (35[degrees]C) compared with low (25[degrees]C) muscle temperatures, likely due to the effect of temperature on the rate of enzymatic reactions.[42] Therefore, in spite of the predominance of the mechanical aspect, the dependence of the initial injury on temperature suggests some involvement of a metabolic component. The mechanical aspect of the initial injury is observed in electron micrographs as focal damage to the ultrastructure of single sarcomeres within specific fibers.[2,6,8] The ultrastructural damage includes displacement of the thick filament to one Z line, crumpling of the interface between thick and thin filaments, and disorganization of the Z lines.[40,41,43]

Force may decrease to zero immediately after an exhaustive protocol of lengthening contractions. During the first few hours, the decrease in maximum force is a function of both fatigue and injury, but the recovery from fatigue appears to be complete by 3 hours (Fig. 4B). Recovery from fatigue is certainly complete by 24 hours, and this is an intrinsic aspect of many definitions of fatigue.[44,45] The magnitude of the initial injury may be estimated from the decrease in force at 3 hours on the assumption that recovery from fatigue is complete and no further injury has occurred that would reduce the force development (Fig. 4B).

Secondary injury. The most direct evidence of a delayed, secondary injury is the increase between 1 and 3 days in the extent and severity of the morphological evidence of injury observed by either light microscopy [20,26] or electron microscopy.[2,8] Unfortunately, a quantitative assessment by these techniques is not possible (see "Criteria of Injury"). Consequently, with complete recovery from fatigue after 24 hours, the best quantitative assessment of the changes in the magnitude of the injury with time is the change in the maximum force developed (Fig. 4B). In mice, the secondary decrease in maximum force is observed between 1 day and 3 days for the EDL muscle[26,28,29,46] and between 3 hours and 1 day for the TBA muscle[28] (Fig. 4B). Other indirect measures, such as enzyme release,[7,15,18,23,36] also agree with the occurrence of a secondary injury between 1 day and 5 days (Fig. 4A). The proximity in time of the peak in the intensity of muscle pain[35,36] with the peaks of the other measures of the secondary injury supports the concept that late-onset muscle soreness arises from the secondary injury to skeletal muscle fibers.

Following the initial injury to individual fibers and subsequent necrosis, if blood flow is impaired significantly, as in ischemic injury, fibers may remain as a necrotic mass of noncontractile tissue and may be infiltrated by fat and connective tissue.[1] In contrast, if the injured fibers have an adequate capillary bed and blood supply, as appears to be the case in contraction-induced injury, phagocytes and macrophages infiltrate the fibers and initiate a cascade of events that lead to the secondary injury.[29] An acute inflammatory response with extensive damage to fibers is observed in cross sections stained with H and E. The phagocytic cells remove the damaged and disrupted myofibrils, cytosolic organelles, and plasmalemma. The basement membrane is highly resistant to injury and generally remains more or less intact.[1]

Because the secondary injury can be eliminated by the pretreatment of animals with an oxygen-free radical scavenger, polyethylene glycol superoxide dismutase (PEG-SOD), the secondary injury appears to be both facilitated and augmented by oxygen-free radicals.[29] With the pretreatment by PEG-SOD, sufficient catalase appears to be present to prevent the aggravation of the initial injury by the oxygen-free radicals. Vitamin E may have a similar role in diminishing the magnitude of the secondary injury,[47] although the role is more controversial and negative results have been reported.[48]

Recovery From Injury

For young animals, after reaching peak deficits of approximately 50% in maximum force from 1 to 3 days after the contraction-induced injury, muscles display a steady recovery to reach a force equivalent to 80% of the control value at 14 days (Fig. 4). The primary determinant of the time required for recovery is the magnitude of the secondary injury. Depending on the severity of the peak injury, full recovery of most aspects of normal structure and function requires from 7 to 3O days.[5,12,26,46]

In mammalian skeletal muscles, a key element in the initiation of the events leading to recovery from a wide variety of injuries to muscle fibers is the activation of satellite cells.[1,49] the satellite cells are located between the basement membrane and the plasmalemma. Both the basement membrane and the satellite cells are resistant to injury and survive exposure to the injurious contractions.[50] A twofold to threefold increase in satellite cell activation has been reported in the muscles of rats run downhill, with the majority of the labeled nuclei near the myotendinous junction.[49] Whether the activation of satellite cells is required for the repair of a highly focal injury to a few sarcomeres within a fiber has not been determined. Furthermore, the factors that activate the satellite cells are not well understood. Following the activation of satellite cells, the cells divide mitotically to form myoblasts, with subsequent fusion of the myoblasts to form myotubes.[1,49] myotubes are observed within the old basement membranes of regenerating fibers 4 to 5 days after injury.[26] the myotubes become immature myofibers and ultimately differentiated muscle fibers.[1] By 14 days, some fibers still show central nuclei, but the recovery in terms of muscle mass and maximum force development is almost complete.[46] Particularly in old animals[51] and in dystrophic animals of all ages, regenerating fibers may exit and reenter breaks in the basement membrane. This process gives rise to complex patterns of branched fibers.[52]

Comparison of Data on Mice and Human Beings

The best comparison of the mouse and human models of contraction-induced injury is based on the decrease in force during the weeks after the initial injury of the mouse TBA muscle[28] and the human elbow flexor muscles[36] (Fig. 4). The secondary injury to the mouse TBA muscle appears to peak at 1 day. The peak is evident because of the decrease in force development from 70% of the control value at 3 hours to 49% at 1 day (Fig. 4B). No data were presented on the maximum voluntary contractions of the elbow flexor muscles of human beings at 3 hours, but presumably, as with the TBA muscle of the mouse, some recovery from fatigue occurred from the strength measured immediately after the 80 lengthening contractions. If this assumption is correct, the secondary injury to human elbow flexor muscles reached a maximum value 1 day after the lengthening contraction protocol when the strength presumably declined to 50% of the initial strength.[36]

After each attained a nadir in force development at 1 day, the mouse TBA muscle and the human elbow flexor muscles displayed a similar steady recovery in force, reaching a value of more than 80% of the initial force values by 14 days. Consequently, the whole sequence of the force loss and recovery is similar for the two sets of data. Coupled with the similarity in the types of injury to muscle fibers by direct measurements with light and electron microscopy, we conclude that the mouse model of contraction-induced injury provides an accurate replica of the human model.

Training to Prevent Contraction-induced Injury

Strength (ability to generate force) is increased by more frequent recruitment and greater loading of muscles during shortening, isometric, or lengthening contractions.[53] Because shortening and lengthening contractions involve velocity as well as load, training with dynamic contractions may also be termed "power training" (power=force x velocity). Power training with movements that involve predominantly lengthening contractions is commonly used in the weight-training programs of athletic teams and in physical therapy programs. With such widespread use, the paucity of experimental studies designed to assess the efficacy and safety of lengthening contractions compared with isometric or shortening contractions in terms of producing gains in strength or power is surprising.[53] Similarly, few studies have been designed utilizing small rodents to test hypotheses regarding the underlying mechanisms responsible for the protection from injury or for the gains in strength and power.[27]

Anecdotal observations of physical activities that cause a high incidence of severe contraction-induced injuries have given rise to the conclusion that if such physical activities are repeated with sufficient time for partial recovery, eventually muscles are "trained" and no injury occurs.[5] Consequently, one can define a "trained" muscle as one that is not injured by a specific protocol of contractions that previously caused injury.[5] Hough[5] and more recently Wernig et al[54] noted that even brief disruptions of training programs of 1 to 5 weeks resulted in the reoccurrence of contraction-induced injury when training was resumed. In spite of these observations, most studies have been short-term and highly variable as to task, with no direct evidence of muscle injury. As a result, the conclusions have been both inconsistent and controversial.

Studies of Human Beings

The inconsistencies in results are evident in studies of both downhill running and forced extension of the elbow flexor muscles. A single exposure to 30 minutes of downhill running provided protection from both enzyme release and muscle soreness following a similar run 6 weeks later.[55] In contrast, no change in the magnitude of enzyme release and little reduction in muscle soreness were observed during a 45-minute downhill run following 2 weeks of downhill running for 5 to 15 minutes 5 consecutive days each week.[10]

Two groups of subjects performed a series of maximal voluntary isometric contractions followed by either six shortening contractions or six lengthening contractions of maximal exertion of the elbow flexor muscles. The training protocols, which were administered 4 days per week for 7 weeks, produced a decrease in force during the first week with reports of muscle soreness.[56] During the subsequent weeks, the soreness disappeared. Throughout the 7 weeks of training, maximum force during isometric contractions did not change. In contrast, the group performing shortening contractions increased the average force developed during shortening and the group performing lengthening contractions showed a similar relative increase during lengthening contractions.

In another study,[36] maximum voluntary contractions during forced stretches of the elbow flexor muscles were performed on three occasions, each separated by 2 weeks (Fig. 6). The enzyme release and muscle soreness were greatest after the first protocol. in spite of the lack of an enzyme release after the second and third protocols, muscle soreness, although reduced, was present. The force, which was approximately 50% of control values immediately after each of the three exercise protocols, returned toward the control value parabolically, but the recovery of maximum force was more rapid and more complete after each of the three repetitions (Fig. 6). A similar investigation demonstrated that 24. lengthening contractions performed by the elbow flexor muscles eliminated the enzyme release and reduced muscle soreness and force deficit when a 70-lengthening-contraction protocol was performed 2 weeks later.[57]

Jones and Rutherford[53] compared the effects of training for 12 weeks with two groups of six subjects each. One group performed a protocol of isometric contractions of the quadriceps femoris muscle of one leg, and the quadriceps femoris muscle in the other leg served as an untrained control muscle. The other group performed shortening contractions with the quadriceps femoris muscle in one leg and lengthening contractions of the quadriceps femoris muscle in the other leg. Training with isometric contractions resulted in a 35% increase in isometric strength, whereas the untrained control muscle showed no change. Forces were 45% higher during lengthening contractions compared with during shortening contractions. in spite of the differences in forces, no difference was observed in the improvement in isometric strength, 11% improvement was observed after training with shortening contractions, and 15% improvement was observed after training with lengthening contractions. Each of the three types of training produced a 5% increase in the total cross-sectional area of the quadriceps femoris muscle.[53] In this report[53] and in a subsequent review,[58] the authors stress the complexity of strength training in terms of the anatomical and physiological mechanisms involved in the increases that occur.

Studies of Small Rodents

At the onset of a program of voluntary wheel running by mice, soleus muscles showed evidence of damage, whereas EDL muscles did not.[54] When mice that had trained daily for 5 months were rested for periods of 1 to 5 weeks, damage to fibers in soleus muscles reappeared 7 days after the voluntary wheel running was resumed. Similarly, soleus muscles in mice exposed to a protocol of 4 days of running interspersed with 21 to 25 days of rest over 12 months showed larger fiber cross-sectional areas and evidence of "split" fibers compared with soleus muscles in continuously run mice and control mice that did not run. The "disrupted" fibers were attributed to "incomplete repair." The difficulty in assessing what has occurred during voluntary wheel running is the same as for any total-body physical activity during which a diversity of contractions are being performed.[22,31] Under these circumstances, the muscle mechanics are unknown and speculation as to the cause of the injury is fruitless.

To test the hypothesis that repeated exposure to a protocol of lengthening contractions that initially caused injury would eventually result in a "trained" muscle that is no longer injured by the same protocol, we designed and built a "shoe" apparatus to measure muscle mechanics in vivo.[59] The apparatus allows for the control of displacement, velocity of contraction, and range of motion of muscles during dorsiflexion and plantar flexion of the ankle of mice.

In a preliminary study, five young mice underwent a training program that consisted of a protocol of 198 lengthening contractions administered to the dorsiflexors once every 7 clays.[27] For each bout of lengthening contractions, the mice were anesthetized and placed on the shoe apparatus. The dorsiflexors were activated by electrical stimulation of the peroneal nerve. During maximal activation, plantar flexion of the ankle by the shoe resulted in lengthening of the dorsiflexor muscle group. The initial protocol of lengthening contractions produced a decrease in force at 3 days to 60% of the initial force, with recovery to 80% by 7 days (similar to Fig. 4B). No decline in force was observed 7 days following the sixth administration of the protocol Fig. 7). Following the sixth repetition of the lengthening contraction protocol, muscles demonstrated an adaptive response, with increases in whole muscle mass and mean single fiber cross-sectional area. The structural and functional adaptations appeared to protect the trained muscles from injury following a lengthening contraction protocol that initially produced injury to untrained muscles. The studies on both mice and human beings support the hypothesis that muscles can be trained to perform lengthening contractions without injury, but training is highly specific to the type of contraction and training must be continuous.

Summary

Small, focal injuries to skeletal muscle fibers caused by their own contractions are a common occurrence, but severe contraction-induced injuries to muscles may also occur. Severe injuries, usually associated with forced stretches of fully activated muscles, are characterized by an initial mechanical injury and a secondary bio-chemical injury. Human beings report late-onset muscle soreness in association with the secondary injury. Depending on the severity of the injury, complete recovery may require from 7 to 30 days. Training with protocols of lengthening (eccentric) contractions produces a hypertrophied, stronger muscle. The "trained" muscle is then capable of performing the protocol of repeated lengthening contractions that previously caused injury without sustaining an injury.

Acknowledgments

We thank Gabriele Wienert and Richard Hinkle for their assistance in the preparation of the manuscript.

References

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JA Faulkner, Phd, Professor of Physiology, Institute of Gerontology, University of Michigan, 300 N Ingalls, Ann Arbor, MI 48109-2007 (USA). Address all correspondence to Dr Faulkner.

SV Brooks, PhD, is Postdoctoral Research Fellow, Institute of Gerontology, University of Michigan.

JA Opiteck is Predoctoral Research Fellow, Institute of Gerontology, University of Nflchigan.

The preparation of this article and the research on which it is based were supported by US Public Health Service National Institute on Aging Grant AG-06157 to Dr Faulkner and a Multidisciplinary Training Grant on Aging (AG-00114) to Dr Brooks and Ms Opiteck.