Exercise-induced Injury Research Articles

Increased mRNAs for procollagens and key regulating enzymes in rat skeletal muscle following downhill running.

The purpose of the study was to investigate pre-translational regulation of collagen expression after a single bout of exercise. We analysed steady-state messenger ribonucleic acid (mRNA) levels for collagen types I, III and IV, alpha- and beta-subunits of prolyl 4-hydroxylase and lysyl oxidase (enzymes modifying procollagen chains), and enzyme activity of prolyl 4-hydroxylase from rat soleus muscle (MS) and the red parts of quadriceps femoris muscle (MQF) after 12 h and after 1, 2, 4, 7 and 14 days of downhill (-13.5 degrees ) treadmill running at a speed of 17 m.min-1 for 130 min. Histological and biochemical assays revealed exercise-induced muscle damage in MQF but not MS. Steady-state mRNA levels for the alpha- and beta-subunits of prolyl 4-hydroxylase in MQF, lysyl oxidase in MS and MQF were increased 12 h after running, whereas prolyl 4-hydroxylase activity did not increase until 2 days after exercise. The mRNA levels for the fibrillar collagens (I and III) and basement membrane type IV collagen significantly increased 1 day and 12 h after exertion, respectively. Peak mRNA levels were observed 2-4 days after running, the increases being more pronounced in MQF than in MS. No significant changes were observed in types I or III collagen at the protein level. Strenuous downhill running thus causes an increase in gene expression for collagen types I and III and their post-translational modifying enzymes in skeletal muscle in a co-ordinated manner. These changes, together with the increased gene expression of type IV collagen, may represent the regenerative response of muscle extracellular matrix to exercise-induced injury and an adaptive response to running exertion.

Dietary control of exertional rhabdomyolysis in horses

To determine whether feeding a low-carbohydrate, high-fat diet would decrease severity of exercise-induced muscle injury in horses with exertional rhabdomyolysis.19 horses with a history of exertional rhabdomyolysis.Case series.Specimens of the semitendinosus or semimembranosus muscle were obtained for histologic examination, and serum creatine kinase (CK) and aspartate transaminase (AST) activities 4 hours after exercise were determined. Horses were then fed a low-carbohydrate, high-fat diet, and serum CK and AST activities 4 hours after exercise were reevaluated at approximately monthly intervals for 3 to 6 months.Serum CK and AST activities 4 hours after exercise were high before any change in diet. All 19 horses had evidence of chronic myopathic change and abnormal glycogen accumulation in muscle biopsy specimens; 11 horses also had evidence of complex polysaccharide accumulation. Adaptation to diet change required approximately 3 to 6 months. Sixteen horses did not have any episodes of exertional rhabdomyolysis after 3 to 6 months of diet change, and 3 horses had mild episodes of exertional rhabdomyolysis following either a reduction in dietary fat intake or restriction in exercise. Postexercise serum CK and AST activities 3 to 6 months after the change in diet were significantly less than initial values.Results indicated that exertional rhabdomyolysis may be a result of abnormal carbohydrate metabolism in some horses. Feeding a diet with low carbohydrate and high fat content may reduce severity of exercise-induced injury in some horses with exertional rhabdomyolysis.

Dietary control of exertional rhabdomyolysis in horses

Objective To determine whether feeding a low-carbohydrate, high-fat diet would decrease severity of exercise-induced muscle injury in horses with exertional rhabdomyolysis. Animals 19 horses with a history of exertional rhabdomyolysis. Design Case series. Procedure Specimens of the semitendinosus or semimembranosus muscle were obtained for histologic examination, and serum creatine kinase (CK) and aspartate transaminase (AST) activities 4 hours after exercise were determined. Horses were then fed a low-carbohydrate, high-fat diet, and serum CK and AST activities 4 hours after exercise were reevaluated at approximately monthly intervals for 3 to 6 months. Results Serum CK and AST activities 4 hours after exercise were high before any change in diet. All 19 horses had evidence of chronic myopathic change and abnormal glycogen accumulation in muscle biopsy specimens; 11 horses also had evidence of complex polysaccharide accumulation. Adaptation to diet change required approximately 3 to 6 months. Sixteen horses did not have any episodes of exertional rhabdomyolysis after 3 to 6 months of diet change, and 3 horses had mild episodes of exertional rhabdomyolysis following either a reduction in dietary fat intake or restriction in exercise. Postexercise serum CK and AST activities 3 to 6 months after the change in diet were significantly less than initial values. Clinical Implications Results indicated that exertional rhabdomyolysis may be a result of abnormal carbohydrate metabolism in some horses. Feeding a diet with low carbohydrate and high fat content may reduce severity of exercise-induced injury in some horses with exertional rhabdomyolysis. (J Am Vet Med Assoc 1998;212:1588–1593).

ECCENTRIC EXERCISE-INDUCED MUSCLE INJURY IN HUMANS 1121

The effects of eccentric exercise on skeletal muscle injury and cytokine accumulation were studied in 5 young (20-32 yr) and 9 older (61-72 yr) men and women who performed either 45 min of downhill running or eccentric cycling at 78 ± 1% of maximum heart rate. Muscle biopsies of the vastus lateralis revealed a significant increase in the percentage of damaged Z-bands [Pre: 16.9 ± 3.2%; lmm Post: 44.2 ± 7.0%, P<0.001; 5 days: 37.3± 5.1%, P<0.005; 12 days: 26.6 ± 3.9%]. Chisquared analysis revealed differences in the distribution of fiber areas in both type I and type II fibers (P<0.005) following exercise. The percentage of type II fibers greater than 5,000 μm2 increased from 10.1% before exercise to 19% and 23.2% 5 and 12 days after exercise, respectively. Interleukin-1β (IL-1β) has been associated with exercise-induced changes in myofibrillar protein turnover. IL-1β levels in muscle 12 days after exercise were correlated to the change in urinary excretion of 3-methylhistidine by 12 days after exercise (R2=.474, P<0.027). These data indicate that the exercise-induced ultrastructural Z-band damage is not influenced by age, and increases in muscle fiber cross sectional area, possibly due to intracellular fluid shifts, occur in response to eccentric exercise-induced injury. The magnitude of the exercise-induced increase in myofibrillar protein degradation is related to the increase in skeletal muscle levels of IL-1β.

Anti-inflammatory medication after muscle injury. A treatment resulting in short-term improvement but subsequent loss of muscle function.

We studied the effect of flurbiprofen, a non-steroidal anti-inflammatory drug, on muscles that had been subjected to exercise-induced injury. The muscles of the anterior compartment in the limbs of rabbits were cyclically activated as the ankle was simultaneously moved through passive plantar flexion every two seconds for thirty minutes. This treatment imposed acute passive lengthening (eccentric contractions) of the maximally contracted muscles of the anterior compartment. After the eccentric contraction-induced muscle injury, one group of rabbits was treated with oral administration of flurbiprofen, two times a day for six days, while the other group of rabbits served as untreated controls. The contractile, histological, and ultrastructural properties of the muscles were measured before the initial exercise and at three, seven, and twenty-eight days afterward. The group that was treated with flurbiprofen demonstrated a more complete functional recovery than the untreated controls at three and seven days but had a deficit in torque and force generation at twenty-eight days. The administration of flurbiprofen also resulted in a dramatic preservation of the intermediate filament protein desmin. After three days, the proportion of fibers of the extensor digitorum longus that lost desmin-staining was significantly greater in the untreated controls than in the treated animals (34 +/- 4.1 compared with 2.9 +/- 1.7 per cent) (p < 0.001), a finding that supports the concept of a short-term protective effect. However, the muscles in the treated animals still mounted a dramatic regenerative response, as indicated by the expression of embryonic myosin. Early in the recovery period (at three days), significantly fewer fibers of the extensor digitorum longus (2.2 +/- 1.4 per cent) expressed embryonic myosin in the treated animals than in the untreated controls (11.8 +/- 1.9 per cent) (p < 0.001). However, at seven days, the expression of embryonic myosin by the muscles from the treated animals (19.5 +/- 11.9 per cent) actually exceeded that of the muscles from the untreated controls (16.2 +/- 4.1 per cent). This finding suggests either a delayed or an ineffectual regenerative response by the muscles in the treated animals.

Intermittent pneumatic compression effect on eccentric exercise-induced swelling, stiffness, and strength loss

Objective: The purpose was to determine if intermittent pneumatic compression (IPC) affects muscle swelling, stiffness, and strength loss resulting from eccentric exercise-induced injury of the elbow flexors. We hypothesized that the compression would decrease swelling and stiffness. Design: Repeated measures design with a before-after trial comparison within each day. Setting: Conducted at a university Somatic Dysfunction Laboratory. Subjects: Twenty-two college women students were studied. They had not been lifting weights or otherwise participating in regular arm exercise for the 6 months before the study. They had no history of upper extremity injury or cardiovascular disease. Interventions: Subjects performed one bout of eccentric exercise at a high load to induce elbow flexor muscle injury. Uniform IPC was applied on the day of exercise and daily for 5 days at 60mmHg, 40 seconds inflation, 20 deflation for 20 minutes. Main Outcome Measures: Measurements of arm circumference, stiffness, and isometric strength were recorded before exercise, then before and after IPC for 5 days after exercise. Passive muscle stiffness was measured on a device that extends the elbow stepwise and records the torque required to hold the forearm at each elbow angle. Results: Circumference and stiffness increased and strength decreased during the 5 days post-exercise ( p < .05). IPC significantly decreased circumference and stiffness most notably on days 2 and 3 after exercise ( p < .05). The strength loss was not affected by IPC. Conclusion: IPC is effective in temporarily decreasing the swelling and stiffness after exercise-induced muscle injury.

Exercise-Induced Heat Injury

Exertional heat illness represents a spectrum of conditions ranging from the benign to the life-threatening. Prompt assessment and treatment can prevent fatalities in those who present as a heat casualty. More importantly, however, these injuries can be prevented from occurring altogether. This article reviews the physiology of thermoregulation and the pathophysiology of heat injuries associated with exercise. Current approaches toward the diagnosis, treatment, and prevention of exercise-induced heat injuries will also be discussed.

Muscle stiffness, strength loss, swelling and soreness following exercise-induced injury in humans.

1. In order to study injury-related changes in muscle stiffness, injury to the elbow flexors of thirteen human subjects was induced by a regimen of eccentric exercise. 2. Passive stiffness over an intermediate range of elbow angles was measured with a device which held the relaxed arm of the subject in the horizontal plane and stepped it through the range of elbow angles from 90 deg to near full extension at 180 deg. The relation between static torque and elbow angle was quite linear over the first 50 deg and was taken as stiffness. 3. Stiffness over this range of angles more than doubled immediately after exercise and remained elevated for about 4 days, and may result from low level myofibrillar activation induced by muscle stretch. 4. Arm swelling was biphasic; arm circumference increased by about 3% immediately after exercise, fell back toward normal, then increased by as much as 9% and remained elevated for as long as 9 days. 5. Ultrasound imaging showed most of the swelling immediately following the exercise to be localized to the flexor muscle compartment; subsequent swelling involved other tissue compartments as well. 6. Muscle strength declined by almost 40% after the exercise and recovery was only slight 10 days later; the half-time of recovery appeared to be as long as 5-6 weeks.

The use of nuclear magnetic resonance to evaluate muscle injury

Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) are new and powerful tools to study tissue biochemistry, and to provide precise anatomical visualization of soft tissue structures. This review focuses on the use of these techniques to study exercise-induced muscle injury. MRS measurements show an increase in the ratio of inorganic phosphate to phosphocreatine (Pi/PCr) 1-7 d after eccentric exercise. This increase in Pi/PCr could be due to either increases in extracellular Pi or small increases in resting muscle metabolism. Increased Pi/PCr is also seen during training programs and may indicate persistent muscle injury. Increased resting Pi/PCr with injury was not associated with altered metabolism during exercise. Elevations in resting Pi/PCr have been used to show increased susceptibility of dystrophic muscle to exercise-induced injury. Progressive clinical deterioration in dystrophic dogs is marked by impaired muscle metabolism, and the presence of low oxidative muscle fibers not seen in normal dogs. MRI shows increased proton T2 relaxation times following eccentric exercise that last up to 80 d after injury, and can reflect muscle edema as well as longer lasting changes in the characteristics of cell water. MRI demonstrate precise localization of the injured area, with large differences in both location and degree of injury in different subjects following the same exercise protocol. Thus, MRS can provide information on the metabolic response to injury, while MRI provides information regarding the site and extent of the injury. These tools have promise in helping to understand exercise-induced muscle injury.

Managing Diabetes in Older Adults

In brief Exercising regularly can have important benefits for older adults with diabetes, including improving insulin sensitivity and cardiovascular fitness. When embarking on a new exercise program, all older diabetic patients should seek the help of health professionals who can determine an appropriate and safe regimen. Special precautions should be taken to lower the risk of developing exercise-induced hypoglycemia or injury due to neuropathy or retinopathy. However, the psychological and physiologic benefits of a regular exercise routine far outweigh any risk to the older person who has diabetes.

Does exercise training alter myocardial creatine kinase MB isoenzyme content?

Skeletal muscle biopsies from highly trained endurance athletes have been shown to contain an increased percentage of the creatine kinase MB (CK-MB) isoenzyme, which has been attributed to continuous regeneration of the skeletal muscle fibers in response to exercise-induced injury. The purpose of this study was to determine whether myocardium undergoes a similar degenerative-regenerative process as a result of exercise training. Fifteen mongrel dogs underwent a 12-wk period of training (N = 8) or cage confinement (N = 7). The animals were then sacrificed, and samples of left and right ventricular myocardium were analyzed for total CK activity and CK-MB isoenzyme content. Percentages of CK-MB were slightly but insignificantly higher from both ventricles of exercise-trained as compared with cage-confined dogs: left ventricle, 4.6 +/- 0.6% vs 3.3 +/- 0.6%, respectively (P = 0.15); right ventricle, 4.0 +/- 0.4% vs 3.0 +/- 0.8%, respectively (P = 0.29). We conclude that chronic exercise training does not induce physiologically important degenerative changes in myocardium.

Protective effect of indomethacin against exercise-induced injuries in mouse skeletal muscle fibers.

The role of prostaglandin synthesis was evaluated by indomethacin administration in the pathogenesis of exercise-induced muscle fiber injuries in soleus and quadriceps femoris muscles of mice. The administration of indomethacin before, during, and after 9 h exertion (s.c., 6 mg/kg during and just after exertion and 1.5-3 mg/kg before exertion and later twice a day) caused a significant histologic protection against exercise injuries and considerably reduced the exercise responses of beta-glucuronidase and glucose-6-phosphate dehydrogenase activities (enzymatic indicators of necrotic lesions in skeletal muscles) on the 2nd post-exercise day. The administration of indomethacin before and during the exertion (3 and 10 mg/kg, respectively) but not after exertion caused only a slight histologic protection while the enzymatic indicators showed a nonsignificant effect.

Autophagic response to strenuous exercise in mouse skeletal muscle fibers.

Strenuous physical exercise induces necrosis of skeletal muscle fibers and increases lysosomal enzyme activities in surviving muscle fibers. This study examines the ultrastructural basis of the stimulation of the lysosomal system in mouse vastus medialis muscle during the appearance and repair of exercise-induced (9 h of running) injuries. Necrotic fibers appeared the day after exercise and an inflammatory response with the replacement of necrotic fibers by phagocytes was highest 2-3 days after exertion. Ultrastructural study of surviving muscle fibers revealed numerous autophagic vacuoles, residual bodies, and spheromembranous structures at the periphery of myofibers, especially in fibers adjacent to necrotic fibers. The autophagic response was most prominent between 2 and 7 days after exertion. Autophagic vacuoles with double or single limiting membranes contained mitochondria at various stages of degradation. Vacuolar and multilamellar structures were also observed in regenerating muscle fibers. The structure of injured skeletal muscle fibers returned to normal within 2 weeks. It is proposed that increased autophagic activity could be related to the breakdown of cellular constituents of surviving muscle fibers to provide structural elements for regenerating muscle fibers.

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.