4. Exercise-induced muscle damage and acute phase response

Muscle contraction and shortening produces a concentric action. However, when skeletal muscle lengthens as it produces force, the result is an eccentric muscle action. An example of this is lifting a weight (concentric action) and lowering it (eccentric action). At the same power output, the oxygen cost of eccentric exercise is lower than that of concentric exercise (ASMUSSEN, 1956), but eccentric exercise has been demonstrated to be a potent cause of muscle damage (NEWHAM et al., 1983; O'REILLY et al., 1987), and increased circulating creatine kinase (CK) activity (EVANS et al., 1986).

Running a marathon can cause extensive skeletal muscle damage (HIKIDA et al., 1983; WARHOL et al., 1985). WARHOL and coworkers (1985) showed a characteristic pattern of muscle damage, with tearing of sarcomeres at the Z-band level followed by movement of fluid into the muscle cells in biopsies taken in the days following the race. Mitochondrial and myofibrillar damage showed progressive repair by 3 to 4 weeks after the marathon. Late biopsies (8 to 12 weeks after the race) showed central nuclei and satellite cells characteristic of a regenerative response. The damage seen by these investigators is very similar to the ultrastructural changes in skeletal muscle resulting from eccentric exercise.

The extent of the ultrastructural evidence of damage is greater well after the initial damaging exercise. FRIDEN et al., (1983) found more damaged muscle fibers 3 days than one hour after high-tension eccentric exercise. NEWHAM and co-workers (1983) also showed that eccentric exercise caused immediate damage, but that biopsies taken 24 to 48 hours after the exercise had more marked damage. These data are indicative of an ongoing process of skeletal muscle repair, consisting of increased degradation of damaged proteins and increased rate of protein synthesis.

Following only one bout of high-intensity eccentric exercise (EVANS, 1986), previously sedentary men showed a prolonged increase in the rate of muscle protein breakdown, evidenced by an increase in urinary 3-methylhistidine/creatinine which peaked 10 days later. In addition, an increase in circulating interleukin-1 (IL-I) levels in these subjects was seen 3 hours after the exercise. Endurance-trained men, performing the same exercise, did not display increased circulating IL-1 levels. However, their pre-exercise plasma IL-1 levels were significantly higher than those seen in the untrained subjects.

Damage to tissue, as well as infection, stimulates a wide range of defense reactions, known as the acute phase response (KAMPSCHMIDT, 1981). The acute phase response is critical for its antiviral and antibacterial actions as well as for promoting the clearance of damaged tissue and subsequent repair. Within hours of injury or exercise (CANNON et al., 1990), the number of circulating neutrophils can increase many-fold. Neutrophils migrate to the site of injury where they phagocytize tissue debris and release factors known to increase protein breakdown, such as lysozyme and oxygen radicals (BABIOR, KIPNES and CURNUTTE, 1973). Greater neutrophil increases have been observed after eccentric exercise than after concentric exercise (SMITH et al., 1989).

While neutrophils have a relatively short half-life (one or two days within tissue (BAINTON, 1988)), the life span of monocytes may be one to two months after migration to damaged tissue (JOHNSTON, 1988). Substantial monocyte accumulation in skeletal muscle was found after completion of a marathon. Following eccentric exercise, monocyte accumulation in muscle was not seen until 4 to 7 days later (JONES et al., 1986; ROUND, JONES and CAMBRIDGE, 1987). In addition to the capability to phagocytize damaged tissue, monocytes secrete cytokines such as IL-1 and tumor necrosis factor (TNF). These and other cytokines mediate a wide range of metabolic events, having an effect on virtually every organ system in the body.

Elevated cytokine levels during infection or injury have different and selective effects. IL-1 mediates an elevated core temperature during infection (CANNON and KLUGER, 1983). In laboratory animals, IL-1 and TNF increase muscle proteolysis and liberation of amino acids (NAWABI et al., 1990), possibly providing substrate for increased hepatic protein synthesis. While circulating IL-1 has been shown to increase acutely as a result of eccentric exercise (EVANS et al., 1983), by 24 hours after the exercise it returned to resting levels. Biopsies of the vastus lateralis taken before, immediately after, and 5 days after downhill running, showed an immediate and prolonged increase in IL-1b (CANNON et al., 1989). This study implicates muscle IL-1b in the post-exercise change in protein metabolism.