Exercise Induced Muscle Damage
& Repair

Introduction

It is well documented that strenuous, unaccustomed exercise causes damage to skeletal
muscle tissue (7,14). Especially during activities in which high peak forces or eccentric
contractions (muscle lengthening) are involved (16). Several direct and indirect indicators
of muscle damage have been observed (23), including: disruption of contractile tissue (11), cellular
accumulation of Calcium (3), delayed onset muscle soreness (DOMS) (7), a prolonged
reduction in muscular strength and range of motion, and an increase in the appearance of
muscle proteins in the blood (7). The damage incurred after eccentric exercise is
temporary and repairable. Furthermore, during the repair process, an adaptation takes
place that makes the muscle more resistant to damage upon performing a second bout of
exercise (7).

Experimental evidence suggests that mechanical stress is a dominant factor for causing
exercise-induced muscle damage (16). Support for this assumption is that the initial damage
occurs to the contractile apparatus. Another argument in favor of mechanical stress is the
observation that muscle damage is much greater using eccentric contractions compared to
concentric contractions (muscle shortening). During eccentric contractions a lower
number of motor units are recruited compared with the same exercise conducted
concentrically(5). The implication is that during eccentric exercise the mechanical stress
per fiber is higher than in concentric exercise. The damage to the contractile elements
after eccentric work is reflected by a reduction in muscular strength and range of motion
for several days (8).

The role of mechanical factors have been studied by McCulley and coworkers (18,19). These investigations used mice muscles that were exposed to lengthening contractions. McCulley and coworkers (19) observed that for inducing structural damage a number of contractile characteristics are important such as: the speed of lengthening, the exercise duration, and the peak forces. However, Lieber and Friden (17) published data suggesting that not the peak force but the speed of lengthening is the dominant factor. They explained this belief by relating the amount of damage in eccentric exercise to the act of cross bride cycling. It is assumed that at low lengthening speeds the cross bridge cycling can keep pace with the change in length. However, at higher lengthening speeds the cross bridge cycling cannot keep pace with the change in length and damage will occur. This damage causes all of the previously mentioned changes in the muscle (19).

 Muscle Damage Indicators

Muscle Soreness

Muscle soreness does not appear until 24 hours after exercise, and peaks at 2-3 days post exercise. Soreness slowly decreases and does not fully subside until 8-10 days after exercise (7). To date the delayed onset of muscle soreness is not fully understood. However, the researcher Smith (24) has presented a series of events to explain the generation of soreness. She believes the damage to muscle and/or connective tissue initiates an immune response which causes an increase in circulating neutrophils. Smith postulates that these neutrophils migrate to the site of injury and are followed by monocytes. Monocytes differentiate into macrophages, which then synthesize large quantities of prostaglandins (PG2). PG2 sensitizes the afferent nerve endings in muscles, which increases the perception of pain (7).

However, it should be noted that Smith based her results on a study using downhill running as its exercise protocol. Downhill running is metabolically stressful in addition to the mechanical stress of the eccentric actions, which causes a unique effect on the immune system that may be unrelated to muscle damage (7). Furthermore, Jones (24), using an exercise regimen involving the forearm flexor muscles, found substantial mononuclear accumulation 7 days after eccentric exercise, long after peak soreness. Depending on the type of exercise, the peak in macrophage accumulation does not coincide with peak soreness (7).

Swelling and edema have also been suggested to cause soreness, likely due to an increase in muscle pressure (7). However, Newham and Jones (20) did not find an increase in muscular pressure after subjects performed eccentric exercise of the forearm flexor muscles. By using girth measures, studies have demonstrated that swelling gradually develops in the days after exercise, reaching peak values at 5 days post exercise. Clearly, the greatest swelling occurs when soreness is decreasing (7). Jones and Round (15) suggest that the most likely explanation for pain is due to an inflammation of the connective tissue. The inflammation would then sensitize mechanoreceptors so that they are easily activated when the muscle is palpated or moving.

Muscle strength

A loss in strength has been associated with unaccustomed bouts of eccentric exercise. In a study by Clarkson (7), using the forearm flexors, immediate strength losses were as much as 50%. Gradually strength is restored but even after 10 days a deficit remains. Studies have shown that muscle fibers are damaged by eccentric exercise (7). In biopsies taken 2 days after eccentric exercise, damage to the myofibrils has been observed, including; Z-line streaming, focal disturbances, and supercontracted sarcomeres (10). It is possible that strength losses are related to the damaged myofibrils. However, according to Friden et al. (10) myofibrillar damage is greater 2 days following eccentric exercise than immediately post exercise. This may indicate that strength losses are independent of myofibrillar damage.

It has yet to be determined whether the initial losses in strength are due to muscle damage, fatigue or a combination of both (7). However, another possibility may be the nervous system. A change in the neural activation patterns could occur that bypass the more severely damaged muscle fibers, thus limiting the number of available muscle fibers for any given contraction (7). Studies by Newham et al. (21) have shown altered EMG patterns immediately and up to 48 hours following eccentric exercise.

Another possible explanation for the prolonged strength loss may be that sarcomeres are stretched out by the lengthening action of eccentric exercise (7). If the lengthening action pulled some of the sarcomeres apart, it would decrease the overlap between the actin and myosin filaments thereby reducing the maximal number of cross bridges that could be formed (7). The ability to generate force (i.e. strength) may be reduced due to this change in sarcomere length. It has yet to be determined whether the recovery in strength and the return of the sarcomere to its pre-exercise length follow the same time period (7).

Range of Motion

Muscle shortening ability is assessed by the flexed arm angle, which is the angle at the elbow taken as the subject attempts to fully flex the forearm, while keeping the elbow fixed at the side (7). Following eccentric exercise there is an immediate increase in this angle, indicating the subject cannot fully flex their arm. Even after 10 days, the subject is unable to attain baseline values (7).

According to Clarkson et al. (7) strength loss and recovery follow a similar time course as the flexed arm angle. This may indicate that the inability to fully flex the forearm could be related to the decrease in muscular strength. Both changes are compatible with the overstretched sarcomere theory (7). As previously mentioned, if there is a decrease in the maximal number of cross bridges that can be formed, a reduction in strength may occur. Furthermore, Clarkson (7) theorizes that the stretched sarcomeres may not be able to produce maximal sliding together of the actin and myosin filaments, and this could affect the ability to fully contract the muscle. If there was a calcium deficiency in the Sarcoplasmic Reticulum (SR), it could be postulated that there would be insufficient calcium to support the continuous cross bridge cycling needed for complete muscle fiber shortening (7). However, no evidence exists to support these theories.

Spontaneous muscle shortening is assessed by the relaxed arm angle, which is the angle at the elbow when the subject allows the arm to hang freely by the side (7). After exercise, this angle immediately becomes more acute and the greatest change is found 3 days post exercise. This angle gradually returns to baseline over the next 7 days (7).

According to Clarkson et al. (7) the decrease in the relaxed arm angle is caused by a shortening of the connective tissue and/or a shortening of the muscle fibers. Any changes in the property of connective tissue or changes in the tendon at its attachments may contribute to the shortening of the muscle (7). Therefore, muscle fiber shortening would result in a decrease in the relaxed arm angle. However, if it is caused by fiber contraction, it is not due to normal means of contraction where the motorneuron activates the fibers (7). Studies have shown that there is no increase in EMG activity associated with the muscle shortening (13). However, the pattern of change follows the same time course of ultrastructural damage, in that damage becomes worse over several days following the exercise. It is theorized that this shortening could be due to an abnormal accumulation of calcium inside the cell (8), most likely caused by gradual loss of sarcolemmal integrity or a dysfunction in the SR. This abnormal increase in calcium could affect the degree of association between the actin and myosin at rest as well as activate specific enzymes that would begin to degrade areas of muscle fibers (7). Furthermore, the presence of calcium in the cell may initiate spontaneous muscle contraction without neural activation.

While the spontaneous shortening of muscle fibers may appear incompatible with the stretched sarcomere theory previously mentioned, it should be noted that stretched sarcomeres would still be able to produce tension, especially in the resting state. It is only at higher tension levels and a more contracted state that the stretched sarcomeres would affect tension generating capacities (7).

Muscle Proteins

Increased levels of muscle proteins in the blood have been routinely used to diagnose muscle disease, and numerous studies have shown these proteins are elevated after eccentric exercise (7,6). Creatine kinase (CK) is the most commonly studied muscle protein (7).

According to Clarkson (7) CK release from the muscle after eccentric exercise may reflect necrosis of focal areas on the muscle fibers. The exercise would initiate a series of events over the 48 hours post exercise period, finally leading to focal necrosis. This series of events could involve an accumulation of calcium inside the cell, either from damage to the membrane or to the SR, that would activate degradation (7).

It should be noted that the plasma CK response after a similar bout of exercise may differ between individuals (16). Furthermore, it is well known that after a comparable amount work males have a higher plasma CK activity than females (16), suggesting that males have more muscle damage than females. Amelink and Bar (1,2) conducted studies that showed androgenic steroids increase the CK efflux and that oestrogens inhibit enzyme release. Furthermore, Van der Meulen et al. (25) conducted a rat study in which male and female rats were exposed to a similar running protocol. In spite of similar workloads a higher CK release was found in the male animals. The histological damage was quantified by microscopical morphometric techniques. In spite of the higher CK release in the male rats no differences in microscopic damage between the male and female animals was found. When comparing the total amount of damage with the cumulative enzyme release, a poor relationship between these two variables was found. Based on enzyme release the amount of damage seems to be overestimated. This means that fiber damage is not necessarily reflected in proportional increases in plasma CK activities (16). This theory is supported by Evans and Cannon (9) who have stated that "the post exercise rise in circulating CK activity is a manifestation of skeletal muscle damage but not a direct indicator of it."
 

Calcium  

As previously mentioned, an increased sarcoplasmic calcium concentration may trigger a number of processes, all contributing to a further deterioration of cellular homeostasis (3). Increased sarcoplasmatic calcium concentration leads to a decreased relaxation, which may be the basis of the transient stiffness and decreased range of motion. Furthermore, it may lead to calcium accumulation in the mitochondria, which will impair ATP generating capacity (16). There is some evidence that ATP levels in the muscle are decreased after overuse (16). A lower ATP generating capacity may affect membrane pumps. This may decrease sodium extrusion and lead to swelling of muscle fibers (10). The increase in free sarcoplasmatic calcium concentration can activate proteolytic enzymes like phospho-lipase A2, that can affect membrane integrity, resulting in an increased permeability (16). In experiments in which the calcium influx has been inhibited, less degenerative changes have been observed (16). 

Adaptations

According to Clarkson et al. (7) it has been found that performance of one bout of high-force eccentric exercise produced an adaptation such that less damage was produced when the same exercise was performed up to several months later. Exactly when and how this adaptation is produced is not known (7). However, it has been found that subjects who perform a second bout of exercise 5 days after performing an initial bout of exercise had already shown an adaptation response (8). Five days after exercise, although the subjects are recovering, they are a little sore and show some decrement in strength and range of motion. However, the changes in strength, range of motion, and soreness after the second bout of exercise performed at the 5 day point were markedly reduced compared with the first bout. Thus, some adaptation has already been produced before the muscle is fully restored (7).

In a study by Nosaka et al. (22), two groups of subjects performed two bouts of the same high-force eccentric exercise. One group performed the exercises 6 weeks apart, and the other group performed the exercises 10 weeks apart. There was a significantly smaller response in isometric strength loss, relaxed arm angle, flexed arm angle, and muscle soreness on bout 2 compared with bout 1 for the group who performed the second bout of exercise 6 weeks later. For the group who performed the second exercise 10 weeks later, there was a significantly smaller response for the relaxed arm angle on the second bout compared with the first bout. However, the level of muscle soreness, flexed arm angle, and isometric strength loss showed similar patterns of response between the first and second bouts (22).

For CK, there was virtually no increase after the second bout for both groups (7). When a subsample of these subjects returned to the laboratory after 6 months and again performed the exercise, the CK response was still reduced (7). At that time, all other measures showed responses that were similar to the first bout. Thus, the adaptation lasts about 6 weeks for strength recovery, muscle shortening ability (flexed arm angle), and muscle soreness; about 10 weeks for spontaneous muscle shortening (relaxed arm angle) ; and about 6 months for CK response (7).

Conclusion

Serial repetitions of maximal effort eccentric actions cause characteristic changes in correlates of muscle damage (7). Peak soreness is experienced 2-3 days post exercise while peak swelling occurs about 5 days post exercise. Maximal strength and the ability to fully flex the arm show the greatest decrements immediately following exercise and then there is a linear restoration over the next 10 days (7). Blood levels of CK do not increase precipitously until 2 days after the exercise, which is also the time when spontaneous muscle shortening is most pronounced. Whether the similarity in the time courses of some of these responses implies that they are caused by similar factors remains to be determined (7).

According to Clarkson et al. (7), performance of one bout of eccentric exercise produces an adaptation such that the muscle is more resistant to damage from a subsequent bout of exercise. The length of the adaptation differed among the measures such that when the exercise regimens are separated by 6 weeks, all measures show a reduction in response on the second, compared with the first bout (7). However, after 10 weeks only CK and spontaneous muscle shortening show a reduction in response (7). Furthermore, after 6 months there is a reduction only in the CK response (7). A combination of cellular factors and neurological factors seems to be involved in the adaptation response (7).

There have been studies concerning the effects of training on exercised induced muscle damage. In one study by Balnave and Thompson (4), they found that training reduces the extent of muscle function impairment, however, they also found no long-lasting repeated bout adaptation. Furthermore, in a recent study by Jakeman and Maxwell (12), they investigated the effects of antioxidant vitamin supplementation upon muscle contractile function following eccentric exercise. It was concluded that prior supplementation of vitamin C may exert a protective effect against exercise induced muscle damage. However, they believe more research needs to be done to obtain conclusive results. So it appears that no real protection against exercised induced muscle damage exists.

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