Markers Of Skeletal Muscle Damage Research Articles

Rapid Increase in Training Load Affects Markers of Skeletal Muscle Damage and Mechanical Performance

The aim of this study was to monitor the changes in indirect markers of muscle damage during 3 weeks (9 training sessions) of stretch-shortening (drop jump) exercise with constant load alternated with steep increases in load. Physically active men (n = 9, mean age 19.1 years) performed a program involving a rapid stepwise increase in the number of jumps, drop height, and squat depth, and the addition of weight. Concentric, isometric maximal voluntary contraction (MVC), and stimulated knee extension torque were measured before and 10 minutes after each session. Muscle soreness and plasma creatine kinase activity were assessed after each session. Steep increments in stretch-shortening exercise load in sessions 4 and 7 amplified the postexercise decrease in stimulated muscle torque and slightly increased muscle soreness but had a minimal effect on the recovery of MVC and stimulated torque. Maximal jump height increased by 7.8 ± 6.3% (p < 0.05), 11.4 ± 3.3% (p < 0.05), and 12.8 ± 3.6% (p < 0.05) at 3, 10, and 17 days after the final training session, respectively. Gains in isometric knee extension MVC (7.9 ± 8.2%) and 100-Hz-evoked torque (9.9 ± 9.6%) (both p < 0.05) were observed within 17 days after the end of the training. The magnitude of improvement was greater after this protocol than that induced by a continuous constant progression loading pattern with small gradual load increments in each training session. These findings suggest that plyometric training using infrequent but steep increases in loading intensity and volume may be beneficial to athletic performance.

Circulating Cell-Free DNA

The phenomenon of circulating cell-free DNA (cfDNA) concentrations is of importance for many biomedical disciplines including the field of exercise physiology. Increases of cfDNA due to exercise are described to be a potential hallmark for the overtraining syndrome and might be related to, or trigger adaptations of, immune function induced by strenuous exercise. At the same time, exercise provides a practicable model for studying the phenomenon of cfDNA that is described to be of pathophysiological relevance for different topics in clinical medicine like autoimmune diseases and cancer. In this review, we are summarizing the current knowledge of exercise-based acute and chronic alterations in cfDNA levels and their physiological significance. The effects of acute exercise on cfDNA concentrations have been investigated in resistance exercises and in continuous, stepwise and interval endurance exercises of different durations. cfDNA concentrations peaked immediately after acute exercise and showed a rapid return to baseline levels. Typical markers of skeletal muscle damage (creatine kinase, uric acid, C-reactive protein) show delayed kinetics compared with the cfDNA peak response. Exercise parameters such as intensity, duration or average energy expenditure do not explain the extent of increasing cfDNA concentrations after strenuous exercise. This could be due to complex processes inside the human organism during and after physical activity. Therefore, we hypothesize composite effects of different physiological stress parameters that come along with exercise to be responsible for increasing cfDNA concentrations. We suggest that due to acute stress, cfDNA levels increase rapidly by a spontaneous active or passive release mechanism that is not yet known. As a result of the rapid and parallel increase of cfDNA and lactate in an incremental treadmill test leading to exhaustion within 15-20 minutes, it is unlikely that cfDNA is released into the plasma by typical necrosis or apoptosis of cells in acute exercise settings. Recently, rapid DNA release mechanisms of activated immune-competent cells like NETosis (pathogen-induced cell death including the release of neutrophil extracellular traps [NETs]) have been discovered. cfDNA accumulations might comprise a similar kind of cell death including trap formation or an active release of cfDNA. Just like chronic diseases, chronic high-intensity resistance training protocols induced persistent increases of cfDNA levels. Chronic, strenuous exercise protocols, either long-duration endurance exercise or regular high-intensity workouts, induce chronic inflammation that might lead to a slow, constant release of DNA. This could be due to mechanisms of cell death like apoptosis or necrosis. Yet, it has neither been implicated nor proven sufficiently whether cfDNA can serve as a marker for overtraining. The relevance of cfDNA with regard to overtraining status, performance level, and the degree of physical exhaustion still remains unclear. Longitudinal studies are required that take into account standardized and controlled exercise, serial blood sampling, and large and homogeneous cohorts of different athletic achievement. Furthermore, it is important to establish standardized laboratory procedures for the measurement of genomic cfDNA concentrations by quantitative real-time polymerase chain reaction (PCR). We introduce a new hypothesis based on acute exercise and chronic exposure to stress, and rapid active and passive chronic release of cfDNA fragments into the circulation.

The biochemical, physiological and psychological consequences of a “1,000 miles in 1,000 hours” walking challenge

The combined effects of 42 days of chronic sleep disruption and repeated hourly bouts of physical exertion have not been described. This case study reports the physiological and psychological demands placed on one individual who walked 1 mile in each consecutive hour for a period of 1,000 h (42 days), covering a total distance of 1,000 miles. The participant walked at a mean speed of 1.75 m/s completing each mile in approximately 15 min. Over the course of the challenge, the individual lost 1.6 kg in body weight. Markers of skeletal muscle damage, increased gradually whilst free testosterone levels decreased over the course of the challenge. Stress hormones increased whilst inflammatory markers (CRP) initially rose but then returned towards baseline over the course of the study. Cognitive motor performance measured via reaction time was maintained throughout the 42 days. The participant also displayed mood states typical of an elite athlete at baseline and throughout the challenge. Participation in this novel '1,000 mile 1,000 h' walking challenge evoked considerable physiological stress in a fit, healthy middle-aged participant but did not markedly alter cognitive performance or mood over the 42-day period.

The possible role of L-carnitine on the skeletal muscle of ovariectomized rats

Low muscle strength is observed during the peri-and postmenopausal periods, when the secretion of ovarian hormones is drastically reduced. It is also a predictive of adverse health events as well as incident mobility limitation and disability. The objective of the present study is to study the biochemical and the histological changes in the skeletal muscle of premature menopause-induced rats and the possible protective role of L-carnitine. Ovariectomized (OVX) rats were gavaged with L-carnitine (100 mg/kg) daily for 60 days starting from the second post-operative day. Serum levels of estradiol and markers of skeletal muscle damage (creatine kinase and lactic dehydrogenase activities) were determined. Light and electron microscopic study of the quadriceps femoris muscle (QFM) specimens were done. OVX rats showed significant decrease in the serum estradiol level with significant increase the markers for skeletal muscle damage. Histopathological examination of the QFM showed degenerated myofibers, apoptotic changes and compensatory hypertrophy. Degenerated mitochondria, multiple lysosomes and lipid droplets among the damaged myofibrils were also noticed. L-carnitine administration to the OVX rats resulted in non-significant change in the serum estradiol level with significant attenuation of skeletal muscle damage either biochemically or histopathologically. In conclusion, L-carnitine administration recovered muscle degeneration after ovariectomy. This finding suggested that L-carnitine could be recommended in the management of post-menopausal myopathy.

Comparison between alternating and pulsed current electrical muscle stimulation for muscle and systemic acute responses

This study compared alternating current and pulsed current electrical muscle stimulation (EMS) for torque output, skin temperature (Tsk), blood lactate and hormonal responses, and skeletal muscle damage markers. Twelve healthy men (23-48 yr) received alternating current EMS (2.5 kHz delivered at 75 Hz, 400 micros) for the knee extensors of one leg and pulsed current (75 Hz, 400 micros) for the other leg to induce 40 isometric contractions (on-off ratio 5-15 s) at the knee joint angle of 100 degrees (0 degrees: full extension). The use of the legs for each condition was counterbalanced among subjects, and the two EMS bouts were separated by 2 wk. The current amplitude was consistently increased to maximally tolerable level, and the torque and perceived intensity were recorded over 40 isometric contractions. Tsk of the stimulated and contralateral knee extensors were measured before, during, and for 30 min after EMS. Blood lactate, growth hormone, testosterone, insulin-like growth factor 1, testosterone, and cortisol were measured before, during, and for 45 min following EMS. Muscle damage markers included maximal voluntary isometric contraction torque, muscle soreness with a 100-mm visual analog scale, and plasma creatine kinase (CK) activity, which were measured before and 1, 24, 48, 72, and 96 h after EMS. No significant differences in the torque induced during stimulation (approximately 30% maximal voluntary isometric contraction) and perceived intensity were found, and changes in Tsk, blood lactate, and hormones were not significantly different between conditions. However, all of the measures showed significant (P<0.05) changes from baseline values. Skeletal muscle damage was evidenced by prolonged strength loss, development of muscle soreness, and increases in plasma CK activity; however, the changes in the variables were not significantly different between conditions. It is concluded that acute effects of alternating and pulsed current EMS on the stimulated muscles are similar.

Effect of short-term creatine supplementation on markers of skeletal muscle damage after strenuous contractile activity

The protective effect of short-term creatine supplementation (CrS) upon markers of strenuous contractile activity-induced damage in human and rat skeletal muscles was investigated. Eight Ironman triathletes were randomized into the placebo (Pl; n = 4) and creatine-supplemented (CrS; n = 4) groups. Five days prior to the Ironman competition, the CrS group received creatine monohydrate (20 g day(-1)) plus maltodextrin (50 g) divided in two equal doses. The Pl group received maltodextrin (50 g day(-1)) only. The effect of CrS (5 g day(-1)/kg body weight for 5 days) was also evaluated in a protocol of strenuous contractile activity induced by electrical stimulation in rats. Blood samples were collected before and 36 and 60 h after the competition and were used to determine plasma activities of creatine kinase (CK), lactate dehydrogenase (LDH), aldolase (ALD), glutamic oxaloacetic acid transaminase (GOT), glutamic pyruvic acid transaminase (GPT), and C-reactive protein (CRP) level. In rats, plasma activities of CK and LDH, muscle vascular permeability (MVP) using Evans blue dye, muscle force and fatigue were evaluated. Activities of CK, ALD, LDH, GOT, GTP, and levels of CRP were increased in the Pl group after the competition as compared to basal values. CrS decreased plasma activities of CK, LDH, and ALD, and prevented the rise of GOT and GPT plasma activities. In rats, CrS delayed the fatigue, preserved the force, and prevented the rise of LDH and CK plasma activities and MVP in the gastrocnemius muscle. CrS presented a protective effect on muscle injury induced by strenuous contractile activities.

Long-term monitoring of patients with infantile-onset Pompe disease on enzyme replacement therapy using a urinary glucose tetrasaccharide biomarker

PurposeTo investigate the correlation of the urinary glucose tetrasaccharide, Glcα1-6Glcα1-4Glcα1-4Glc, (Glc4) with skeletal muscle glycogen content and the long-term clinical response to enzyme replacement therapy with recombinant human acid alpha glucosidase in infantile Pompe disease. MethodsEighteen patients, ≤6 months old, were enrolled in a clinical trial of enzyme replacement therapy for up to 142 weeks. Urinary Glc4, skeletal muscle glycogen, and other clinical and laboratory assessments were made at baseline and at regular intervals. Urinary Glc4 was determined using an isotope-dilution tandem mass spectrometric assay. The clinical response to treatment was defined according to the motor function response. Trends in urinary Glc4 were correlated with the clinical response and compared with serum enzyme markers of skeletal muscle damage, creatine kinase, aspartate aminotransferase, and alanine aminotransferase. ResultsUrinary Glc4, in contrast to the serum markers, correlated closely with skeletal muscle glycogen content and with the clinical response. Patients with the best response to treatment maintained the lowest levels of Glc4 throughout the trial. ConclusionThe results from this study support the use of urinary Glc4 for monitoring patients with infantile-onset Pompe disease on therapy.

Influence Of Hormone Replacement Therapy With Maximal Eccentric Exercise On Estrogen Receptor Coregulators And Skeletal Muscle Damage In Postmenopausal Women

The use of hormone replacement therapy (HRT) is a potential treatment to relieve symptoms of menopause and prevent the onset of disease such as osteoporosis in postmenopausal women. Although estrogen has a possible protective effect against exercise-induced skeletal muscle damage, it is unclear if HRT therapy enhances estrogen receptor (ER) activity in skeletal muscle at rest and following resistance exercise. PURPOSE: To evaluate changes in the mRNA gene expression of ER coregulators (SRC and SMRT) and markers of skeletal muscle damage (CK, LDH, and TNF-a) in postmenopausal women following a high-intensity resistance exercise bout. METHODS: Fourteen postmenopausal women were divided into two groups: Control, women not using HRT (n=6, 59±2 yr, 63±7 kg), or HRT, women using traditional HRT (n=8, 59±1 yr, 89.5±8.4 kg). Both groups performed 10 sets of 10 maximal eccentric repetitions of single-leg extension on the Cybex dynamometer at 60°/s with 20 second rest periods between sets. Two muscle biopsies of the vastus lateralis were obtained from the exercised leg at baseline and 4 hours after the exercise bout. mRNA gene expression was determined using RT-PCR for SRC, SMRT, and TNF-a. Blood draws were performed at baseline and 3 days post-exercise to measure CK and LDH. Independent t-tests were performed to test group differences (Control vs HRT). A probability level of p≤0.05 was used to determine statistical significance with Bonferroni adjustments. RESULTS: We observed significantly greater changes in mRNA expression of SRC and SMRT (p≤0.01) and significantly lower changes in mRNA expression of TNF-a (p≤0.01) in the HRT group compared to controls following the exercise bout. mRNA expression of SRC significantly increased (p≤0.01) and mRNA expression of SMRT significantly decreased (p≤0.01) following the exercise bout in both groups. CK and LDH levels were significantly greater post-exercise (p≤0.01) in the Control group. CONCLUSIONS: These data suggest a single bout of maximal eccentric exercise significantly enhances ER activity with greater response present in postmenopausal women using HRT. Postmenopausal women not using HRT experienced greater muscle damage after exercise indicating a possible protective effect of HRT against exercise-induced skeletal muscle damage. Keywords: SRC, SMRT, muscle damage

Acute and timing effects of beta-hydroxy-beta-methylbutyrate (HMB) on indirect markers of skeletal muscle damage

BackgroundWhile chronic β-Hydroxy β-Methylbutyrate (HMB) supplementation (≥ 2 wk) lowers exercise induced muscle damage, its acute or timing effects have not been examined. The purpose of this study was to investigate the acute and timing effects of oral HMB supplementation on serum creatine kinase (CK), lactate dehydrogenase (LDH), muscle soreness, and maximal voluntary contraction (MVC).MethodsSixteen non-resistance trained men (22 ± 2 yrs) were assigned to HMB-Pre or HMB-Post groups. In a crossover design, all subjects performed 55 maximal eccentric knee extension/flexion contractions on 2 occasions on either the right or left leg. HMB-Pre (N = 8) randomly received 3 grams of either a placebo or HMB before and a placebo after exercise. HMB-Post (N = 8) received a placebo before and either 3 grams of HMB or a placebo after exercise. Muscle damage tests were recorded before, at 8, 24, 48, and 72 hrs post exercise.ResultsThere was a reduction in MVC and an increase in soreness in the quadriceps and hamstrings following exercise (p < 0.001). Although HMB-Pre approached significance in attenuating soreness for the quadriceps (p = 0.07), there was no time × group effect. Serum indices of damage increased, peaking at 48 hrs for CK (773%) (p < 0.001) and 72 hrs for LDH (180%) (p < 0.001). While there were no time × group effects of HMB on CK and LDH, post hoc analysis revealed that only HMB-Pre showed no significant increase in LDH levels following exercise.ConclusionOur findings suggest no clear acute or timing effects of HMB supplementation. However, consuming HMB before exercise appeared to prevent increases in LDH.

The Effect Of Exhaustive Intermittent Cycling Exercise On Plasma Markers Of Muscle Damage

PURPOSE: The purpose of this study was to determine the effects of exercise consisting of exhaustive intermittent cycling on several plasma markers of skeletal muscle damage, specifically interleukin (IL)-6 and creatine kinase (CK). METHODS: Twelve well trained, male cyclists (VO2max=62.29±5.60ml*kg−1*min−1) completed 6 bouts of exhaustive intermittent cycling exercise approximately one week apart. The exercise bouts consisted of multiple 2-min intervals at 90% Pmax, followed by a 2-min recovery bout at 50% Pmax,. When the subject could no longer maintain the required self selected cadence, the higher workload was reduced by 10% Pmax. This non-stop but interval exercise continued until the subject could no longer maintain cadence when at 50%Pmax. Venous blood samples were taken pre- and immediately post-exercise, 2-hr post-exercise, and 24-hr post exercise. RESULTS: Pre-to post-exercise, CK increased from 106.92±55.63IU/L to 119.74±61.41IU/L (p<0.05), there was also an increase from pre-to 2-hr postexercise (124.88±80.89 IU/L, p<0.05) as well as from pre-to 24-hr post exercise (172.62±158.98 IU/L, p<0.05). Interestingly there was no difference from post-to 2-hr post-exercise despite the rise in CK from 2-hr post-to 24-hr post-exercise (p<0.05). Likewise, from pre-to post-exercise IL increased from 1.63±2.30pg/ml to 3.90±2.61pg/ ml (p<0.05), and increase from pre-to 3.45±2.85pg/ml 2-hr post-exercise (p<0.05). While there was no difference from post-to 2-hr post-exercise, IL decreased from both post-to 2-hr post-exercise as well as 24-hr post-exercise (1.54±2.34pg/ml, p<0.05). There was a significant (p<0.05) positive correlation between total work done and the change in both CK (r=0.263) and IL (r=0.441) pre-to post-exercise. Similarly, exercise time significantly (p<0.05) correlated with the change in CK (r=0.319) and IL (r=0.563). Also, there was a significant correlation between the change in CK and IL (r=0.219, p<0.05). CONCLUSIONS: These data suggest that the change in pre-to post-exercise IL and CK is dependent on the amount of work completed during, and or the duration of, the exercise bout. In addition, these data also suggest that there may be a relationship between the secretion of IL, with the leakage of CK, from the damaged muscle cell. This study was funded by the Hershey Co.

A prospective case-control survey of laboratory markers of skeletal muscle damage during HIV disease and antiretroviral therapy.

In a case-control prospective study of approximately 1000 HIV-infected patients, a 15% incidence of muscle laboratory abnormalities was found. No difference emerged between patients with altered creatine phosphokinase levels and controls in the duration of HIV infection, antiretroviral therapy and its duration, selected drug combinations, disease stage, mean CD4 cell count and viraemia, lipodystrophy syndrome, metabolic and bone abnormalities, and eventual myotoxic therapies, except a prevalence of male sex and a longer duration of stavudine administration.

Cardiac troponin and β-type myosin heavy chain concentrations in patients with polymyositis or dermatomyositis

Cardiac troponin T (cTnT), cardiac troponin I (cTnI), myosin heavy chains (MHC), myoglobin, creatine kinase (CK), and creatine kinase isoenzyme MB (CKMB), were measured in blood samples from 39 polymyositis (PM) or dermatomyositis (DM) patients without clinical evidence for cardiac involvement to evaluate their clinical usefulness in this patient population. MHC, myoglobin, and CKMB were frequently elevated and correlated with each other and with disease severity. Undetectable cTnI in all but one patient indicated that MHC was released from skeletal muscle, thereby providing the first laboratory evidence of frequent slow-twitch muscle fibre-necrosis in patients with PM or DM. CKMB was elevated in 51%, cTnT in 41%, and cTnI in only 2.5% of patients. cTnI did not correlate with other markers or with disease severity scores. The close correlations found between cTnT and skeletal muscle damage markers and the relationship between cTnT with disease severity without clinical evidence for myocardial damage suggest a release of cTnT from skeletal muscle. The relationship of cTnT with disease severity indicates a possible role of the marker for risk stratification. However, the prognostic values of cardiac troponins and other muscle damage markers in PM/DM patients remain to be compared in prospective outcome trials.