Desmin and actin alterations in human muscles affected by delayed onset muscle soreness: a high resolution immunocytochemical study

Lack of staining for desmin in muscles in animal models of eccentric exercise has been suggested to reflect disruption of the desmin intermediate filament network and proposed to cause disruption of the myofibrillar apparatus and deterioration of muscle fibers. In a recent study, we examined muscle biopsies from persons who had performed different eccentric exercise protocols, which induced delayed onset muscle soreness (DOMS). We were unable to verify that loss of staining for desmin was a feature of sore muscles. Nevertheless, we observed changes in the desmin cytoskeleton, but the meaning of the observations was not conclusive. In the present study, a high resolution immunocytochemical method was used to investigate the changes of desmin and actin in human muscles following a bout of eccentric exercise that lead to DOMS 2-3 days post-exercise. Biopsies were taken before exercise and 1 h and 2-3 and 7-8 days after exercise. Phalloidin, a ligand that labels filamentous actin, and anti-desmin antibodies were used to stain semithin (approximately 0.5 micro m) cryosections. At 1 h post-exercise, the staining of actin and desmin did not differ from the controls, whereas in biopsies taken 2-3 and 7-8 days after exercise, 12.5% (SD 5.8%) and 6.1% (SD 2.3%) fibers showed areas of increased staining for actin. Corresponding values for fibers with increased staining for both actin and desmin were 8.7% (SD 3.9%) and 11.4% (SD 4.6%), respectively. We suggest that the increased staining of actin and desmin reflects an increased synthesis of these proteins as part of an adaptation process following the unaccustomed eccentric exercise.     

The mode of myofibril remodelling in human skeletal muscle affected by DOMS induced by eccentric contractions

Myofibrillar Z-disc streaming and loss of the desmin cytoskeleton are considered the morphological hallmarks of eccentric contraction-induced injury. The latter is contradicted by recent studies where a focal increase of desmin was observed in biopsies taken from human muscles with DOMS. In order to determine the effects of eccentric contraction-induced alterations of the myofibrillar Z-disc, we examined the distribution of alpha-actinin, the Z-disc portion of titin and the nebulin NB2 region in relation to actin and desmin in DOMS biopsies. In biopsies taken 2-3 days and 7-8 days after exercise, we observed a significantly higher number of fibres showing focal areas lacking staining for alpha-actinin, titin and nebulin than in biopsies taken from control or 1 h after exercise. None of these proteins were part of Z-disc streamings but instead they were found in distinct patterns in areas characterised by altered staining for desmin and actin. These were preferentially seen in regions with increased numbers of sarcomeres in parallel myofibrils. We propose that these staining patterns represent different stages of sarcomere formation. These findings therefore support our previous suggestion that muscle fibres subjected to eccentric contractions adapt to unaccustomed activity by the addition of new sarcomeres.     

Inflammatory markers CD11b, CD16, CD66b, CD68, myeloperoxidase and neutrophil elastase in eccentric exercised human skeletal muscles

The aim of the present study was to investigate leucocyte markers, CD11b, CD16, CD66b, CD68, myeloperoxidase and neutrophil elastase on skeletal muscle biopsies from biceps brachii after unaccustomed eccentric exercise followed by the second bout of exercise 3 weeks later. The subjects (10 subjects received COX-2 inhibitor (Celecoxib) and 13 subjects received placebo) were divided into three categories: mild, moderate and severe effect of eccentric exercise, according to the reduction and recovery of muscle force-generating capacity after performing 70 maximal eccentric actions with elbow flexors on an isokinetic dynamometer. The results showed that the CD66b antibody was applicable for localization of neutrophils in human skeletal muscle, whereas the other studied neutrophil markers recognized also other leucocytes than neutrophils. The number of CD66b positive cells in skeletal muscle was very low and was not affected by the exercise. The macrophage marker CD68 showed reactivity also against satellite cells and fibroblast-like cells in skeletal muscle and therefore cannot be applied as a quantitative value for inflammatory cells. Skeletal muscle fibre injury, shown as dystrophin negative fibres, was observed approximately in half of the biopsies at 4 and 7 days after the first exercise bout in the categories moderate and severe effect of eccentric exercise. These subjects represent the most prominent loss in muscle force-generating capacity both at the category and the individual levels. Furthermore, deformed skeletal muscle fibres were observed in five subjects in these categories after the second bout of exercise. The present results suggest that neutrophils are not involved in skeletal muscle fibre injury and the reduction in muscle force-generating capacity after a single bout of eccentric exercise is a good indirect indicator of muscle damage in humans. Furthermore, prolonged regeneration process could be one of the reasons for impaired peripheral muscle function after high-force eccentric exercise.     

Segmental muscle fiber lesions after repetitive eccentric contractions

Immunohistochemical and electron-microscopic techniques were used to analyze the extensor digitorum longus muscles of New Zealand White rabbits 1 h, 1 day, 3, 7, and 28 days after repetitive eccentric contractions. Loss of the cytoskeletal protein desmin was the earliest manifestation of injury. Apart from 1 h post-exercise, all desmin-negative fibers stained positively with antibody to plasma fibronectin, indicating loss of cellular integrity accompanying cytoskeletal disruption. Fiber sizes were significantly increased from 1–7 days after exercise. The large (hyaline) fibers found in histological sections after repetitive eccentric contractions resulted from segmental hypercontraction of the fiber. This phenomenon occurred proximally and distally to plasma membrane lesions of the muscle fiber and necrosis and manifested itself as very short sarcomere lengths. Thus, in serial sections, staining characteristics, sizes and shapes of one and the same fiber often varied dramatically. We conclude that the following sequence of events occurs: cytoskeletal disruptions, loss of myofibrillar registry, i.e., Z-disk streaming and A-band disorganization, and loss of cell integrity as manifested by intracellular plasma fibronectin stain, hypercontracted regions, and invasion of cells. When a fiber is disrupted, the remaining intact fibers apparently take up the tension put on the muscle and later fewer fibers are subjected to eccentric contractions.     

Effect of exercise-induced muscle damage on the blood lactate response to incremental exercise in humans

Eccentric muscle actions are known to induce temporary muscle damage, delayed onset muscle soreness (DOMS) and muscle weakness that may persist for several days. The purpose of the present study was to determine whether DOMS-inducing exercise affects blood lactate responses to subsequent incremental dynamic exercise. Physiological and metabolic responses to a standardised incremental exercise task were measured two days after the performance of an eccentric exercise bout or in a control (no prior exercise) condition. Ten healthy recreationally active subjects (9 male, 1 female), aged 20 (SD 1) years performed repeated eccentric muscle actions during 40 min of bench stepping (knee high step; 15 steps · min⁻¹). Two days after the eccentric exercise, while the subjects experienced DOMS, they cycled on a basket loaded cycle ergometer at a starting work rate of 150 W, with increments of 50 W every 2 min until fatigue. The order of the preceding treatments (eccentric exercise or control) was randomised and the treatments were carried out 2 weeks apart. Two days after the eccentric exercise, all subjects reported leg muscle soreness and exhibited elevated levels of plasma creatine kinase activity (P < 0.05). Endurance time and peak V˙O₂ during cycling were unaffected by the prior eccentric exercise. Minute volume, respiratory exchange ratio and heart rate responses were similar but venous blood lactate concentration was higher (P < 0.05) during cycling after eccentric exercise compared with the control condition. Peak blood lactate concentration, observed at 2 min post-exercise was also higher [12.6 (SD 1.4) vs 10.9 SD (1.3) mM; P < 0.01]. The higher blood lactate concentration during cycling exercise after prior eccentric exercise may be attributable to an increased rate of glycogenolysis possibly arising from an increased recruitment of Type II muscle fibres. It follows that determination of lactate thresholds for the purpose of fitness assessment in subjects experiencing DOMS is not appropriate. Accepted: 27 September 1997     

Re-Evaluation of Sarcolemma Injury and Muscle Swelling in Human Skeletal Muscles after Eccentric Exercise

The results regarding the effects of unaccustomed eccentric exercise on muscle tissue are often conflicting and the aetiology of delayed onset muscle soreness (DOMS) induced by eccentric exercise is still unclear. This study aimed to re-evaluate the paradigm of muscular alterations with regard to muscle sarcolemma integrity and fibre swelling in human muscles after voluntary eccentric exercise leading to DOMS. Ten young males performed eccentric exercise by downstairs running. Biopsies from the soleus muscle were obtained from 6 non-exercising controls, 4 exercised subjects within 1 hour and 6 exercised subjects at 2–3 days and 7–8 days after the exercise. Muscle fibre sarcolemma integrity, infiltration of inflammatory cells and changes in fibre size and fibre phenotype composition as well as capillary supply were examined with specific antibodies using enzyme histochemistry and immunohistochemistry. Although all exercised subjects experienced DOMS which peaked between 1.5 to 2.5 days post exercise, no significant sarcolemma injury or inflammation was detected in any post exercise group. The results do not support the prevailing hypothesis that eccentric exercise causes an initial sarcolemma injury which leads to subsequent inflammation after eccentric exercise. The fibre size was 24% larger at 7–8 days than at 2–3 days post exercise (p<0.05). In contrast, the value of capillary number per fibre area tended to decrease from 2–3 days to 7–8 days post exercise (lower in 5 of the 6 subjects at 7–8 days than at 2–3 days; p<0.05). Thus, the increased fibre size at 7–8 days post exercise was interpreted to reflect fibre swelling. Because the fibre swelling did not appear at the time that DOMS peaked (between 1.5 to 2.5 days post exercise), we concluded that fibre swelling in the soleus muscle is not directly associated with the symptom of DOMS.     

Effects of a protease supplement on eccentric exercise-induced markers of delayed-onset muscle soreness and muscle damage

This investigation examined the effects of a protease supplement on selected markers of muscle damage and delayed-onset muscle soreness (DOMS). The study used a double-blinded, placebo-controlled, crossover design. Twenty men (mean +/- SD age = 21.0 +/- 3.1 years) were randomly assigned to either a supplement group (SUPP) or a placebo group (PLAC). All subjects were tested for unilateral isometric forearm flexion strength, hanging joint angle, relaxed arm circumference, subjective pain rating, and plasma creatine kinase activity and myoglobin concentration. The testing occurred before (TIME1), immediately after (TIME2), and 24 (TIME3), 48 (TIME4), and 72 (TIME5) hours after a bout of eccentric exercise. During these tests, the subjects in the SUPP group ingested a protease supplement. The subjects in the PLAC group took microcrystalline cellulose. After testing at TIME5 and 2 weeks of rest, the subjects were crossed over into the opposite group and performed the same tests as during visits 1-5, but with the opposite limb. Overall, isometric forearm flexion strength was greater (7.6%) for the SUPP group than for the PLAC group, despite nearly identical (difference = 0.14 N.m, p = 0.940) mean strength values before (TIME1) the eccentric exercise protocol. There were no between-group differences for hanging joint angle, relaxed arm circumference, subjective pain ratings, and plasma creatine kinase activity and myoglobin concentration from TIME1 to TIME5. These findings provided initial evidence that the protease supplement may be useful for reducing strength loss immediately after eccentric exercise and for aiding in short-term strength recovery. The protease supplement had no effect, however, on the perception of pain associated with DOMS or the blood markers of muscle damage.     

Evidence for myofibril remodeling as opposed to myofibril damage in human muscles with DOMS: an ultrastructural and immunoelectron microscopic study

The myofibrillar and cytoskeletal alterations observed in delayed onset muscle soreness (DOMS) caused by eccentric exercise are generally considered to represent damage. By contrast our recent immunohistochemical studies suggested that the alterations reflect myofibrillar remodeling (Yu and Thornell 2002; Yu et al. 2003). In the present study the same human muscle biopsies were further analyzed with transmission electron microscopy and immunoelectron microscopy. We show that the ultrastructural hallmarks of DOMS, Z-disc streaming, Z-disc smearing, and Z-disc disruption were present in the biopsies and were significantly more frequent in biopsies taken 2–3 days and 7–8 days after exercise than in those from controls and 1 h after exercise. Four main types of changes were observed: amorphous widened Z-discs, amorphous sarcomeres, double Z-discs, and supernumerary sarcomeres. We confirm by immunoelectron microscopy that the main Z-disc protein alpha-actinin is not present in Z-disc alterations or in the links of electron-dense material between Z-discs in longitudinal register. These alterations were related to an increase of F-actin and desmin, where F-actin was present within the strands of amorphous material. Desmin, on the other hand, was seen in less dense regions of the alterations. Our results strongly support that the myofibrillar and cytoskeletal alterations, considered to be the hallmarks of DOMS, reflect an adaptive remodeling of the myofibrils.     

Role of the calcium-calpain pathway in cytoskeletal damage after eccentric contractions.

The mechanism(s) underlying eccentric damage to skeletal muscle cytoskeleton remain unclear. We examined the role of Ca(2+) influx and subsequent calpain activation in eccentric damage to cytoskeletal proteins. Eccentric muscle damage was induced by stretching isolated mouse muscles by 20% of the optimal length in a series of 10 tetani. Muscle force and immunostaining of the cytoskeletal proteins desmin, dystrophin, and titin were measured at 5, 15, 30, and 60 min after eccentric contractions and compared with the control group that was subjected to 10 isometric contractions. A Ca(2+)-free solution and leupeptin (100 microM), a calpain inhibitor, were applied to explore the role of Ca(2+) and calpain, respectively, in eccentric muscle damage. After eccentric contractions, decreases in desmin and dystrophin immunostaining were apparent after 5 min that accelerated over the next 60 min. Increased titin immunostaining, thought to indicate damage to titin, was evident 10 min after stretch, and fibronectin entry, indicating membrane disruption, was evident 20 min after stretch. These markers of damage also increased in a time-dependent manner. Muscle force was reduced immediately after stretch and continued to fall, reaching 56 +/- 2% after 60 min. Reducing extracellular calcium to zero or applying leupeptin minimized the changes in immunostaining of cytoskeletal proteins, reduced membrane disruption, and improved the tetanic force. These results suggest that the cytoskeletal damage and membrane disruption were mediated primarily by increased Ca(2+) influx into muscle cells and subsequent activation of calpain.     

Sensory mapping of the upper trapezius muscle in relation to consecutive sessions of eccentric exercise

The aim of this study was to evaluate the changes in pressure pain sensitivity maps in untrained subjects over 2 subsequent sessions of eccentric exercise (ECC) expected to result in (a) delayed onset muscle soreness (DOMS) and (b) adaptation/recovery, respectively. Eleven healthy male subjects participated in this study. Pressure pain threshold (PPT), rate of perceived exertion (RPE), pain intensity, soreness area drawing, maximal voluntary contraction (MVC), and shoulder range of motion were assessed in session 1 before, immediately after, and 24 hours after ECC. The ECC protocol that was used to induce DOMS consisted of 50 eccentric contractions of the right shoulder that were divided into 5 bouts, including 10 contractions at MVC level separated by a 2-minute resting period. Session 2 was identical to session 1 and performed exactly 1 week later. There was only a significant increase in the RPE assessed before the exercise and 24 hours after the exercise in session 1 (p = 0.001). The average PPT only decreased significantly from before the exercise (660.2 ± 76.2 kPa) to 24 hours after the exercise (435.6 ± 59.3 kPa) in session 1 (p = 0.016). The present study confirmed a heterogeneous distribution of mechanical sensitivity before and after sessions of ECC. The first session of ECC underlined increased mechanical sensitivity because of DOMS, whereas the second session reflected an adaptation process. Our results support the potential role of ECC bouts in training regimens.     

Piroxicam fails to reduce myocellular enzyme leakage and delayed onset muscle soreness induced by isokinetic eccentric exercise

To test the hypothesis that delayed onset muscular soreness (DOMS) following intense eccentric muscle contraction could be due to increased production of prostaglandin E(2) (PGE(2)), ten healthy male subjects were studied. Using a double-blind randomized crossover design, each subject performed two isokinetic tests separated by a period of at least 6 weeks: once with placebo, and once with piroxicam (Feldene((R))). They were given one capsule containing either placebo or piroxicam (20 mg) per day for 6 days with initial doses given starting 3 days prior to isokinetic testing. Exercise consisted of eight stages of five maximal contractions of the knee extensor and flexor muscle groups of both legs separated by 1 min rest phases, on a Kin Trex device at 60( degrees )/s angular velocity. The subjective presence and intensity of DOMS were evaluated using a visual analogue scale immediately after, and 24 and 48 h after each test. The mean plasma concentration of PGE(2) measured at rest and after exercise was significantly lower in the group treated with piroxicam (p < 0.05). However, statistical analysis (two-way ANOVA test) revealed that exercise did not cause any significant change of mean plasma PGE(2) over time in either of the two groups. Eccentric work was followed by severe muscle pain in extensor and flexor muscle groups. Maximal soreness was noted 48 h postexercise. Serum creatine kinase activity and the serum concentration of myoglobin increased significantly, and reached peak values 48 h after exercise in both experimental conditions (p < 0.001). By paired t-test, it appeared that there were no significant differences in the serum levels of these two markers of muscle damage between the two groups at any time point. We conclude that: (1) oral administration of piroxicam fails to reduce muscle damage and DOMS caused by strenuous eccentric exercise; and (2) the hypothetical role of increased PGE(2) production in eccentric exercise-induced muscle damage, DOMS, and reduced isokinetic performance is not substantiated by the present results.     

L-arginine Supplementation Protects Exercise Performance and Structural Integrity of Muscle Fibers after a Single Bout of Eccentric Exercise in Rats

Eccentric exercise is known to disrupt sarcolemmal integrity and induce damage of skeletal muscle fibers. We hypothesized that L-arginine (L-Arg; nitric oxide synthase (NOS) substrate) supplementation prior to a single bout of eccentric exercise would diminish exercise-induced damage. In addition, we used N-nitro-L-arginine methyl ester hydrochloride (L-NAME; NOS inhibitor) to clarify the role of native NOS activity in the development of exercise-induced muscle damage. Rats were divided into four groups: non-treated control (C), downhill running with (RA) or without (R) L-Arg supplementation and downhill running with L-NAME supplementation (RN). Twenty four hours following eccentric exercise seven rats in each group were sacrificed and soleus muscles were dissected and frozen for further analysis. The remaining seven rats in each group were subjected to the exercise performance test. Our experiments showed that L-Arg supplementation prior to a single bout of eccentric exercise improved subsequent exercise performance capacity tests in RA rats when compared with R, RN and C rats by 37%, 27% and 13%, respectively. This outcome is mediated by L-Arg protection against post-exercise damage of sarcolemma (2.26- and 0.87-fold less than R and RN groups, respectively), reduced numbers of damaged muscle fibers indicated by the reduced loss of desmin content in the muscle (15% and 25% less than R and RN groups, respectively), and diminished µ-calpain mRNA up-regulation (42% and 30% less than R and RN groups, respectively). In conclusion, our study indicates that L-Arg supplementation prior to a single bout of eccentric exercise alleviates muscle fiber damage and preserves exercise performance capacity.     

Effects of step exercise on muscle damage and muscle Ca2+ content in men and women

Eccentric exercise often produces severe muscle damage, whereas concentric exercise of a similar load elicits a minor degree of muscle damage. The cellular events initiating muscle damage are thought to include an increase in cytosolic Ca. It was hypothesized that eccentric muscle activity in humans would lead to a larger degree of cell damage and increased intracellular Ca accumulation in skeletal muscle than concentric activity would. Furthermore, possible differences between men and women in muscle damage were investigated following step exercise. Thirty-three healthy subjects (18 men and 15 women) participated in a 30-minute step exercise protocol involving concentric contractions with 1 leg and eccentric contractions with the other leg. Muscle Ca content, maximal voluntary contraction (MVC), and muscle enzymes in the plasma were measured. In a subgroup of the subjects, T2 relaxation time was measured by magnetic resonance imaging. No significant changes were found in muscle Ca content in vastus lateralis biopsy specimens in women or in men. Following step exercise, MVC decreased in both legs of both genders. The women had a significantly larger strength decrease in the eccentric leg than the men had on postexercise day 2 (p < 0.01). Plasma creatine kinase increased following step exercise, with a sevenfold higher response in women than in men on day 3 (p < 0.001). The women, but not the men, had an increase in T2 relaxation time in the eccentrically working adductor magnus muscle, peaking on day 3 (75%) (p < 0.001). In conclusion, step exercise does not lead to Ca accumulation in the vastus lateralis but does induce muscle damage preferentially in the eccentrically working muscles, considerably more in women than in men. This indicates that gender-specific step training programs may be warranted to avoid excessive muscle damage.     

Sarcolemmal excitability as investigated with M-waves after eccentric exercise in humans.

It has been shown that intensive eccentric muscle actions lead to prolonged loss of muscle force and sarcolemmal damage. This may lead to a reduction in the excitability of the sarcolemma and contribute to the functional deficit. Experiments were carried out to test sarcolemmal excitability after eccentric elbow flexor exercise in humans. Electrically elicited surface compound muscle action potential (M-wave) properties from 30s stimulation trains (20Hz) were analyzed in biceps brachii muscle immediately after, 1h and 48h after the exercise. M-wave area, amplitude, root mean square and duration were reduced immediately after the eccentric exercise. However, no such reduction could be observed 48h after the exercise, although the maximal voluntary isometric and eccentric torques were still depressed by 12.2+/-9% (P<0.001) and 17.7+/-9% (P<0.001), respectively. Acute increase in plasma concentrations of K(+) and Ca(2+) were also observed after the eccentric exercise. These findings suggest that eccentric exercise may acutely decrease sarcolemmal excitability, which seems to be partially related to increased extracellular ion concentrations. However, disturbance of sarcolemmal excitability is not the major factor determining eccentric exercise induced prolonged loss of muscle strength, because no prolonged impairment was observed in any of the studied M-wave parameters.     

The effects of estrogen on indices of skeletal muscle tissue damage after eccentric exercise in postmenopausal women

This study examined if estrogen (E) usage (in the form of hormone replacement therapy [HRT]) has a protective effect on skeletal muscle damage in postmenopausal women. Nine postmenopausal women (age 55.2 +/- 9.9 [mean +/- SD]) performed two exercise sessions at 70% of their maximal heart rate on HRT (E-HI) and without HRT (E-LO; following a 28-45 day HRT washout). All subjects followed a condition order of E-HI then E-LO with at least 42 days between exercise sessions. Serum creatine kinase (CK), perceived delayed onset muscle soreness (DOMS), and maximal quadriceps isometric force (MIF) were taken pre-exercise, 24, 48 and 72-hr post exercise. E-HI and E-LO conditions produced a rise in CK (p < 0.001) after exercise; but CK after E-HI was greater than in E-LO (p < 0.001) at 24 hours and at 48 hours. DOMS was significantly elevated at 24, 48, and 72-hr post each exercise session (p < 0.05). The greatest peak DOMS score occurred during the E-HI condition. MIF was similarly reduced after each exercise session (p < 0.05). These results suggest elevated E does not offer a protective effect to skeletal muscle; however, design limitations (i.e., condition order) confound the present data. Interestingly, an association between peak-CK during the E-LO condition and the number of washout days (r = +0.707, p < 0.05) between conditions existed. This suggests a longer washout period may be necessary to elucidate the actual E effects on skeletal muscle. These findings suggest that more work correcting for the present design limitations is warranted on this topic.     

Gender effects on trapezius surface EMG during delayed onset muscle soreness due to eccentric shoulder exercise.

The purpose of this study was to investigate gender-specific motor control strategies during eccentric exercise and delayed onset muscle soreness (DOMS) in the shoulder region. Twelve healthy males and females participated in the study. Eccentric shoulder exercises were conducted on the dominant shoulder while the other side served as control. The exerted force, range of shoulder elevation, rating of perceived exertion, pain intensity, and surface electromyography (EMG) from the trapezius muscles were recorded and analyzed. A significant decrease in exerted force during exercise was only found in males despite similar rating of perceived exertion among genders. During eccentric exercise: males showed increasing root mean square (RMS) of the EMG while a decrease occurred for females, no difference between genders in mean power frequency of the EMG were seen. During static and dynamic contractions: no differences between genders in pain intensity or RMS were observed; RMS of the exercised side were lower than that of the control side (P<0.05) at 24 h after exercise. The results indicated a more prominent muscle fatigue resistance in females compared with males and mobilization of different muscle activation strategies during eccentric exercise. A protective adaptation to DOMS, i.e. decrease in RMS values was found with no gender differences.     

Influence of estrogen on markers of muscle tissue damage following eccentric exercise.

This study tested the hypothesis that estrogen levels of women influences the development of a muscle-tissue damage (creatine kinase, CK) marker and delayed onset muscle soreness (DOMS) following eccentric exercise. Seventeen oral contraceptive (OC) users and ten eumenorrheic (EU) subjects completed a 30-min downhill running bout at approximately 60% VO2max. The OC completed the exercise during the mid-luteal phase (day 22.9 +/- 1.5; high estrogen) while the EU did their exercise in the mid-follicular phase (day 9.6 +/- 4.4; low estrogen) of the menstrual cycle, respectively. The CK activity and DOMS were assessed pre-exercise, immediately post-, 24, 48 and 72 h post-exercise. ANOVA results indicated that there was a significant increase in CK activity in response to the downhill run (p < 0.001), and the interaction of group x time was significantly different (p < 0.01). The OC group had lower CK at 72 h post-exercise than did the EU group. Pre-exercise estrogen levels correlated with the overall mean CK (r = -0.43, p < 0.05) and 72 h (r = -0.38, p < 0.05) responses, respectively. Exercise caused an increase in DOMS in both groups (p < 0.001); but, no significant interaction was observed. These findings suggest that elevated estrogen levels have a protective effect on muscle tissue following eccentric exercise. The mechanism of this protective effect is unclear but may be related to the anti-oxidant characteristics and membrane stability properties associated with estrogen and its derivatives.     

High specific torque is related to lengthening contraction-induced skeletal muscle injury.

Animal models implicate multiple mechanical factors in the initiation of exercise-induced muscle injury. Muscle injury has been widely studied in humans, but few data exist regarding the underlying cause of muscle injury. This study sought to examine the role of torque per active muscle volume in muscle injury. Eight subjects performed 80 electrically stimulated [via electromyostimulation (EMS)] eccentric contractions of the right and left quadriceps femoris (QF) through an 80 degrees arc at 120 degrees /s. Specific torque was varied by applying 25-Hz EMS to one thigh and 100-Hz EMS to the contralateral thigh. Transverse relaxation time (T2) magnetic resonance images of the QF were collected before and 3 days after the eccentric exercise bouts. Injury was assessed via changes in isometric force and ratings of soreness over the course of 14 days after exercise and by determining changes in T2 and muscle volume 3 days after exercise. The 100-Hz EMS induced greater force loss (P < 0. 05), soreness (P < 0.05), change in muscle volume (P = 0.03), and volume of muscle demonstrating increased T2 (P = 0.005) than the 25-Hz EMS. In addition, injury was found to be similar across the QF in all but the most proximal regions of the QF. Our findings suggest that, in humans, high torque per active volume during lengthening muscle contractions is related to muscle injury.     

Eccentric exercise-induced injury to rat skeletal muscle

These experiments were designed to study skeletal muscle pathology resulting from eccentric-biased exercise in rats. The effects on the muscles of running on a treadmill on a 0 degrees incline (similar amounts of concentric and eccentric contractions), down a 16 degrees incline (primarily eccentric contractions), and up a 16 degrees incline (primarily concentric contractions) at 16 m . min-1 for 90 min were assessed by following postexercise changes in 1) plasma creatine kinase and lactate dehydrogenase activities, 2) glucose-6-phosphate dehydrogenase (G-6-PDase) activity (bio- and histochemically) in the physiological extensor muscles, and 3) histological appearance of the muscles. The data indicate the following. 1) Whereas all exercise protocols resulted in elevations of plasma enzymes immediately after running, only eccentric exercise caused late phase elevations 1.5-2 days postexercise. 2) Significant increases in muscle G-6-PDase activity, which were always associated with accumulations of mononuclear cells, always occurred within some muscles of each extensor group 1-3 days following downhill and uphill running and did not occur following level running; the increases in activity were usually of lower magnitude in the muscles of uphill runners than in those of downhill runners; the deeply located, predominantly slow-twitch muscles were most affected by both down- and uphill running. 3) Muscle histology demonstrated localized disruption of normal banding patterns of some fibers immediately after exercise and accumulations of macrophages in the interstitium and in some (less than 5%) muscle fibers by 24 h postexercise in the deep slow muscles of the antigravity groups. Although the data generally indicated that eccentric exercise causes greater injury to the muscles, questions remain.