Priscilla M. Clarkson

MUSCLE FUNCTION AFTER EXERCISE-INDUCED MUSCLE DAMAGE AND RAPID ADAPTATION

This brief review focuses on the time course of changes in muscle function and other correlates of muscle damage following maximal effort eccentric actions of the forearm flexor muscles. Data on 109 subjects are presented to describe an accurate time course of these changes and attempt to establish relationships among the measures. Peak soreness is experienced 2-3 d postexercise while peak swelling occurs 5 d postexercise. Maximal strength and the ability to fully flex the arm show the greatest decrements immediately after exercise with a linear restoration of these functions over the next 10 d. Blood creatine kinase (CK) levels increase precipitously at 2 d after 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. 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 differs among the measures such that when the exercise regimens are separated by 6 wk, all measures show a reduction in response on the second, compared with the first, bout. After 10 wk, only CK and muscle shortening show a reduction in response. After 6 months only the CK response is reduced. A combination of cellular factors and neurological factors may be involved in the adaptation process.

Exercise-Induced Muscle Damage and Adaptation

SummaryNovel, unaccustomed exercise has been shown to result in temporary, repairable skeletal muscle damage. After exhaustive endurance exercise, muscle damage can be produced by metabolic disturbances associated with ischaemia. Extensive disruption of muscle fibres also occurs after relatively short term eccentric exercise where high mechanical forces are generated. Biopsies taken after repetitive eccentric muscle actions have revealed broadening, streaming and, at times, total disruption of Z-discs. Muscles that develop active tension eccentrically also become sore, lose inherent force-producing capability, and show a marked release of muscle proteins into the circulation. Because creatine kinase (CK) is found almost exclusively in muscle tissue, it is the most common plasma marker of muscle damage. Despite the universal use of CK as a marker, several factors with regard to efflux and clearance remain unexplained. Also the large intersubject variability in response to exercise complicates its interpretation.Damage progresses in the postexercise period before tissues are repaired. However, the mechanism to explain exercise-induced muscle damage and repair is not well defined. Among the factors that may influence the damage and repair processes are calcium, lysosomes, connective tissue, free radicals, energy sources, and cytoskeletal and myofibrillar proteins.Physical conditioning results in an adaptation such that all indicators of damage are reduced following repeated bouts of exercise. Recently, investigators have suggested that the prophylactic effect of training may be due to performance of a single initial exercise bout. Following a second bout of exercise performed 1 to 6 weeks after the first bout, there is a reduction in morphological alterations and performance decrements and a profoundly reduced elevation in plasma CK levels. Several hypotheses have been presented to explain the repeated bout or rapid training effect. Stress-susceptible fibres may be eliminated or susceptible areas within a fibre may undergo necrosis and then regenerate. These regenerated fibres, along with adaptations in the connective tissue, may provide greater resistance to further insult.

Changes in indicators of inflammation after eccentric exercise of the elbow flexors

This study examined muscle swelling and changes in inflammatory markers in the blood following eccentric exercise-induced muscle damage. Subjects (N = 14) who had not been involved in a resistance training program performed 24 maximal eccentric actions of the elbow flexors. Muscle swelling was assessed by measures of the upper arm circumference (CIR), ultrasonography (USG), and magnetic resonance imaging (MRI). Plasma concentrations of interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6, tumor necrosis factor-alpha, and plasma levels of C-reactive protein, cortisol, and zinc were analyzed. Established indicators of muscle damage (maximal isometric force, range of motion, muscle soreness, and plasma creatine kinase, aspartate aminotransferase, and lactate dehydrogenase activities) were also measured. All measures, including CIR and USG, except for MRI, were assessed immediately before and after and for 5 d post-exercise. MRI was taken at pre- and 1, 3, 6, 10, 23, 31, and 58 d post-exercise. All muscle damage indicators changed significantly after exercise. A large increase in CIR (> 20 mm) was found 4-5 d after exercise, and this coincided with USG, showing an increase in muscle thickness. The echointensity of USG increased with the enlargement of the elbow flexors. MRI displayed enlargement of the biceps brachii and brachialis cross-sectional area that started at 1 d, and lasted until 23 d, post-exercise. The most profound increase in the enlargement and signal intensity of the MRI was found 3 or 6 d after exercise. However, none of the plasma levels of inflammatory makers showed significant muscle swelling, which is indicative of muscle edema, but the inflammatory responses after exercise appear to be different from those accompanying infection or tissue injury.

Effect of Statins on Skeletal Muscle Function

Background— Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied. Methods and Results— The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (P<0.0001) with atorvastatin. There were no significant changes in several measures of muscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (P=0.69). Conclusions— These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.

Neuromuscular dysfunction following eccentric exercise.

This study examined the effects of exercise-induced muscle damage on tremor and proprioception components of neuromuscular function. Six male and six female volunteers (aged 18-30 yr) performed 50 maximal eccentric muscle actions using the forearm flexors of the nondominant arm. Forearm flexor tremor and perception of voluntary force and joint position were monitored to assess changes in neuromuscular function. Data were analyzed using REANOVA. Serum creatine kinase activity increased from a baseline value of 68 +/- 13 IU.l-1 to 2849 +/- 852 IU.l-1 5 d after exercise (P < 0.05). This was accompanied by prolonged impaired joint range of motion (P < 0.01) and reduced maximum strength (P < 0.01). Muscle soreness peaked 3 d postexercise (P < 0.01; Wilcoxon test). Tremor amplitude was increased (P < 0.01) until 48 h after exercise, whereas the power frequency spectrum was unaffected. Perception of joint position at elbow angles of 1.57 rad (P < 0.01) and 2.09 rad (P < 0.05) and perception of force (P < 0.01) were significantly impaired when the control arm acted as the reference. Joint positions were more accurately reproduced when the experimental arm acted as its own reference. The increase in tremor amplitude and loss of proprioceptive function in the days after damage-inducing eccentric exercise suggest significant impairment of neuromuscular function.

Skeletal muscle stiffness and pain following eccentric exercise of the elbow flexors.

&NA; Stiffness and pain occurring after eccentric exercise have been studied in human elbow flexor muscles. Increased muscle stiffness and flexion deformities of the elbow developed immediately after the exercise and were greatest 1–4 days later. Muscle tenderness and pain experienced during elbow extension developed more slowly but were both maximal at the same time as the muscle stiffness. EMG recordings at times when there was pain and flexion deformity showed the biceps to be electrically silent. This demonstrates that the pain was not due to sustained electrical activity in the muscle and the flexion was a consequence of shortening of non‐contractile elements, presumably the connective tissue. It is suggested that some response to damaged connective tissue may cause increased mechanical sensitivity of muscle receptors which, in turn, gives rise to pain when the muscle is stretched or pressed.

Time course of muscle adaptation after high force eccentric exercise.

SummaryThe repeated bout effect on changes in muscle damage indicators was examined in two groups of subjects following two bouts of 70 maximal eccentric actions of the forearm flexors. Fourteen college age female subjects were placed into two groups. The two bouts were separated by 6 weeks (n=6), and 10 weeks (n = 8). The subjects performed the same amount of work for the bouts. The muscle damage indicators were isometric strength (STR), relaxed elbow joint angle (RANG), flexed elbow joint angle (FANG), perceived muscle soreness ratings (SOR), and plasma creatine kinase activity (CK). These measures were obtained pre-exercise and 5 days following each bout. The first bout showed significant changes in all measures over time for both groups (P<0.01). For the 6-week group, significantly smaller changes in RANG (P < 0.01), SOR (P<0.05), and CK (P<0.01), as well as significantly faster recoveries (P<0.05) for STR and FANG were produced in the second bout. For the 10-week group, significantly smaller changes in RANG (P<0.05) and CK (P<0.01) were demonstrated by the second bout, but no significant difference was found for STR, FANG, and SOR between bouts 1 and 2. Changes in CK were still significantly smaller than that of the first bout when 6 subjects (3 subjects from each group) performed the same exercise 6 months after the second bout, but no difference in other measures. It is concluded that the length of the adaptation effect varies among the indicators of muscle damage and that the duration of the adaptation for CK is dramatic.

Force recovery after eccentric exercise in males and females.

Abstract In this study we investigated force loss and recovery after eccentric exercise, and further characterized profound losses in muscle function (n=192 subjects – 98 males, 94 females; population A). Maximal voluntary contractile force (MVC) was assessed before, immediately after, and at 36 and 132 h after eccentric exercise. Two groups were then established (A1 and A2). Group A1 demonstrated a >70% reduction in MVC immediately after exercise, but were recovering at 132 h after exercise. These subjects performed a follow-up MVC 26 days later (n=32). Group A2 demonstrated a >70% reduction in MVC immediately post-exercise, but still exhibited a >65% reduction in force at 132 h post-exercise; these subjects also performed a follow-up MVC every 7 days until full recovery was established (n=9). In population A, there was a 57% reduction in MVC immediately post-exercise and a 67% recovery by 132 h post-exercise (P < 0.01), with no significant gender differences (P > 0.05). In group A1, although more females (two-thirds) showed large force losses after exercise, these females demonstrated greater %MVC recovery at 132 h post-exercise (59% vs 44%) and at 26 days post-exercise (93% vs 81%) compared to the males. In group A2, MVC recovery occurred between 33 and 47 days post-exercise. In conclusion, 21% of all subjects showed a delayed recovery in MVC after high-force eccentric exercise. Although there were no significant gender differences in force loss, a disproportionately larger number of females demonstrated force reductions of >70%. However, their recovery of force was more rapid than that observed for the males who also demonstrated a >70% force loss.

Changes in Ubiquitin Proteasome Pathway Gene Expression in Skeletal Muscle With Exercise and Statins

Objective—Statins are safe medications but have side effects including myalgia and rhabdomyolysis. How statins provoke muscle damage is not known, but this effect is exacerbated by exercise. Methods and Results—Healthy subjects took Atorvastatin (80 mg/daily) or placebo for 4 weeks. Biopsies of both vastus lateralis muscles were performed 8 hours after eccentric exercise (known to result in muscle soreness and damage) of the left leg at baseline and the right leg after statin/placebo treatment. Gene expression was determined using Affymetrix GeneChips, and selected genes confirmed by polymerase chain reaction (qRT-PCR). Atorvastatin had little effect on gene expression at rest. When combined with exercise, 56 genes were differentially expressed with 18% involved in the ubiquitin proteasome pathway (UPP) and 20% involved in protein folding and catabolism, and apoptosis. Conclusion—This is the first investigation to our knowledge to implicate involvement of the UPP in skeletal muscle in response to combined exercise and statin treatment, possibly explaining the onset of myalgia with exertion. Statins may alter the response of muscle to exercise stress by altering the action of the UPP, protein folding, and catabolism, disrupting the balance between protein degradation and repair.

Drugs and sport - Research findings and limitations

SummaryMany types of drugs are used by athletes to improve performance. This paper reviews the literature on 3 categories of drugs: those that enhance performance as stimulants (amphetamines, ephedrine, and cocaine), those that are used to reduce tremor and heart rate (β-blockers) and those involved in bodyweight gain or loss (anabolic-androgenic steroids, growth hormone, β2-agonists, and diuretics). Limitations of research on these drugs as they relate to performance enhancement are also discussed.The numerous studies that have assessed the effects of amphetamines on performance report equivocal results. This may be due to the large interindividual variability in the response to the drug and the small sample sizes used. Most studies, however, show that some individuals do improve exercise performance when taking amphetamines, which may be attributed to their role in masking fatigue. As a stimulant, ephedrine has not been found to improve performance in the few studies available. More recently, ephedrine has been purported to be effective as a fat burner and used by athletes to maintain or improve muscle mass. Although research on individuals with obesity supports the use of ephedrine for fat loss, no studies have been done on athletes. The few studies of cocaine and exercise suggest that little to no performance gains are incurred from cocaine use. Moreover, the sense of euphoria may provide the illusion of better performance when, in actuality, performance was not improved or was impaired.β-Blockers have been found to reduce heart rate and tremor and to improve performance in sports that are not physiologically challenging but require accuracy (e.g. pistol shooting). However, there is evidence that some individuals may be high responders to β-blockers to the extent that their heart rate response is so blunted as to impair performance.Although equivocal, several studies have reported that anabolic-androgenic steroids increase muscle size and strength. However, most studies are not well controlled and use insufficient drug doses. One recent well controlled study did find an increase in muscle mass and strength with supraphysiological doses, and the improvements were greater in participants who were also resistance training. There is little information available on the effects of growth hormone on muscle mass or performance in athletes, although data suggest that growth hormone administration does not increase muscle protein synthesis. β2-Agonists, such as clenbuterol and salbutamol, when administered orally appear to improve muscular strength due to their potential role in increasing muscle mass. However, studies have not been done using athletes. Diuretics result in a loss of body water and hence bodyweight that can be advantageous for sports with strict bodyweight classifications. There is insufficient evidence on possible performance decrements in the field that could result from dehydration induced by the diuretics.Overall, the most significant concern in studies of drug use is the large interindividual variability in responses to a drug. Further studies are needed to understand why some individuals are more responsive than others and to assess whether the responses are consistent for a given individual. Most studies of drug effectiveness have not used athletes. The effectiveness of many drugs may be reduced in highly trained athletes because there is a lower margin for improvement.