Pulsed electromagnetic fields attenuate human musculocutaneous nerve damage induced by biceps eccentric contractions.

Pulsed electromagnetic field (PEMF) therapy, a noninvasive treatment, has shown promise in mitigating nerve damage. However, unaccustomed exercises, such as eccentric contractions (ECCs), can damage both muscle and nerve tissue. This study investigated whether magnetic stimulation (MS) with PEMF could aid in nerve recovery after ECCs in the elbow flexors. Twenty participants were randomly assigned to either a control (CNT) or an MS group. Following ECCs, we measured the latency of the M-wave in the musculocutaneous nerve as an indicator of nerve function. Additionally, isometric torque, range of motion, and muscle pain were assessed for muscle function. Interestingly, only the CNT group exhibited a significant increase in latency on Day 2 (p < 0.05). The MS group, on the other hand, displayed an earlier recovery trend in isometric torque, range of motion, and muscle soreness. Notably, muscle soreness significantly decreased immediately after MS treatment compared to pretreatment levels. These findings suggest that MS treatment can effectively attenuate nerve damage induced by ECCs exercise.

Cigarette smoke exposure impairs early-stage recovery from lengthening contraction-induced muscle injury in male mice.

The use of tobacco cigarettes produces locomotor muscle weakness and fatigue intolerance. Also, smokers and chronic obstructive pulmonary disease patients have a greater incidence of muscle injury and a deficient myogenic response. However, the effects of smoke exposure on the recovery from eccentric exercise-induced muscle injuries are unknown. Mice were exposed daily to cigarette smoke (CS) or room air (Air) for 4 months; the anterior crural muscles from one limb were injured by a lengthening contractions protocol (LCP) and recovered for 7 days. Lung compliance was greater, and body weights were lower, in CS-exposed than in the Air group. In LCP-subjected limbs, CS exposure lowered tibialis anterior myofiber cross-sectional area, decreased the size of centrally nucleated myofibers, and decreased extensor digitorum longus (EDL) mass, but did not affect EDL force from both limbs. CS exposure upregulated the mRNA levels of several myogenic (Pax7, Myf5, nNOS) genes in the EDL. The combination of CS exposure and LCP decreased Myf5 and nNOS mRNA levels and exacerbated pro-inflammatory mRNA levels. These data suggest that smoke exposure leads to an excessive pro-inflammatory response in regenerating muscle that is associated with a lower muscle mass recovery from a type of injury that often occurs during strenuous exercise.

Time-of-day effects on ex vivo muscle contractility following short-term satellite cell ablation.

Muscle isometric torque fluctuates according to time-of-day with such variation owed to the influence of circadian molecular clock genes. Satellite cells (SCs), the muscle stem cell population, also express molecular clock genes with several contractile-related genes oscillating in a diurnal pattern. Currently, limited evidence exists regarding the relationship between SCs and contractility, although long-term SC ablation alters muscle contractile function. Whether there are acute alterations in contractility following SC ablation and with respect to the time-of-day is unknown. We investigated whether short-term SC ablation affected contractile function at two times of day and whether any such alterations led to different extents of eccentric contraction-induced injury. Using an established mouse model to deplete SCs, we characterized muscle clock gene expression and ex vivo contractility at two times-of-day (morning: 0700 and afternoon: 1500). Morning-SC+ animals demonstrated ∼25%-30% reductions in tetanic/eccentric specific forces and, after eccentric injury, exhibited ∼30% less force-loss and ∼50% less dystrophinnegative fibers versus SC- counterparts; no differences were noted between Afternoon groups (Morning-SC+: -5.63 ± 0.61, Morning-SC-: -7.93 ± 0.61; N/cm2; P < 0.05) (Morning-SC+: 32 ± 2.1, Morning-SC-: 64 ± 10.2; dystrophinnegative fibers; P < 0.05). As Ca++ kinetics underpin force generation, we also evaluated caffeine-induced contracture force as an indirect marker of Ca++ availability and found similar force reductions in Morning-SC+ vs. SC- mice. We conclude that force production is reduced in the presence of SCs in the morning but not in the afternoon, suggesting that SCs may have a time-of-day influence over contractile function.NEW & NOTEWORTHY Muscle isometric torque fluctuates according to time-of-day with such variation owed to molecular clock regulation. Satellite cells (SCs) have recently demonstrated diurnal characteristics related to muscle physiology. In our work, force production was reduced in the presence versus absence of SCs in the morning but, not in the afternoon. Morning-SC+ animals, producing lower force, sustained lesser degrees of injury versus SC- counterparts. One potential mechanism underpinning lower forces produced appears to be lower calcium availability.

The acute and repeated bout effects of multi-joint eccentric exercise on physical function and balance in older adults.

PURPOSE: Eccentric muscle actions generate high levels of force at a low metabolic cost, making them a suitable training modality to combat age-related neuromuscular decline. The temporary muscle soreness associated with high intensity eccentric contractions may explain their limited use in clinical exercise prescription, however any discomfort is often alleviated after the initial bout (repeated bout effect). Therefore, the aims of the present study were to examine the acute and repeated bout effects of eccentric contractions on neuromuscular factors associated with the risk of falling in older adults. METHODS: Balance, functional ability [timed up-and-go and sit-to-stand], and lower-limb maximal and explosive strength were measured in 13 participants (67.6 ± 4.9 year) pre- and post-eccentric exercise (0, 24, 48, and 72 hr) in Bout 1 and 14 days later in Bout 2. The eccentric exercise intervention was performed on an isokinetic unilateral stepper ergometer at 50% of maximal eccentric strength at 18 step‧min-1 per limb for 7 min (126 steps per limb). Two-way repeated measures ANOVAs were conducted to identify any significant effects (P ≤ 0.05). RESULTS: Eccentric strength significantly decreased (- 13%) in Bout 1 at 24 hr post-exercise; no significant reduction was observed at any other time-point after Bout 1. No significant reductions occurred in static balance or functional ability at any time-point in either bout. CONCLUSION: Submaximal multi-joint eccentric exercise results in minimal disruption to neuromuscular function associated with falls in older adults after the initial bout.

Fatigue-induced changes in hamstrings' active muscle stiffness: effect of contraction type and implications for strain injuries.

PURPOSE: Hamstring strain injuries may occur due to differential fatigue and compromised mechanical properties among the hamstring muscles. We examined (1) the effect of fatigue on hamstrings active muscle stiffness, and (2) whether contraction type affects active muscle stiffness changes during a submaximal fatiguing task. METHODS: Nine healthy males completed 99 submaximal knee flexions in isometric (ISO), concentric (CON), and eccentric (ECC) conditions. We measured the knee flexor maximal voluntary torque (MVT) (pre/post), shear wave velocity (SWV) during contraction and transverse relaxation times (T2) (pre/post) in biceps femoris long head (BFlh), semitendinosus (ST), and semimembranosus (SM) muscles. RESULTS: MVT decreased substantially after all conditions (- 18.4 to - 33.6%). The average relative torque sustained during the task was lower in CON than ISO and ECC, but absolute torque was similar. SWV interindividual responses were highly variable across muscles and contraction types. On average, BFlh SWV tended to increase in ISO (0.4 m/s, 4.5%, p = 0.064) but decreased in ECC condition (- 0.8 m/s, - 7.7%, p < 0.01). ST SWV decreased in CON (- 1.1 m/s, - 9.0%, p < 0.01), while it remained unchanged in ISO and ECC. SM SWV decreased in CON (- 0.8 m/s, - 8.1%, p < 0.01), but it was unaffected in ISO and variable in ECC. CONCLUSION: Fatigue has a differential effect on the mechanical properties of the constituent hamstring muscles, as measured with shear wave elastography, depending upon contraction type. We found preliminary evidence that BFlh is more fatigued than ST or SM during eccentric contractions, which may explain its susceptibility to strain injuries.

Passive force enhancement is not abolished by shortening of single rabbit psoas fibres.

Passive force enhancement is defined as the increase in steady-state passive force following deactivation of an actively stretched muscle compared to the corresponding passive force following passive stretching of the muscle. Passive force enhancement has been associated with contributing to the residual force enhancement property, providing stability to sarcomeres, and preventing sarcomeres from over-stretching during eccentric muscle action. Despite its functional importance, the molecular mechanisms underlying passive force enhancement remain unknown. Specifically, it remains unknown how passive force enhancement develops and how it is abolished. Incidental observations on cat soleus muscles led to the speculation that passive force enhancement is abolished when the actively stretched muscle is deactivated and then passively shortened to its pre-stretched length. Here, we tested this hypothesis using skinned fibres from rabbit psoas and rejected it. Rather, we found that passive force enhancement increased following shortening of the fibres to their pre-stretched length (2.4 µm), and furthermore, that the passive force enhancement increased by 70-106% when the shortening and subsequent stretch to the original length (3.6 µm) increased in duration (200 ms, 6 s, and 14 s). These results indicate that passive force enhancement increases during a shortening-stretch cycle, and that this increase is time-dependent. We propose that this increase in passive force enhancement is caused by titin; specifically, with a refolding of titin's immunoglobulin domains that were unfolded during the active fibre stretching that produced the residual and passive force enhancement. Molecular level experiments are required to test this proposal.

Muscular contraction's therapeutic potential for cancer-induced wasting.

Skeletal muscle atrophy and dysfunction contribute to morbidity and mortality in patients with cancer. Cachexia pathophysiology is highly complex, given that perturbations to the systemic cancer environment and the interaction with diverse tissues can contribute to wasting processes. Systemic interleukin 6 (IL-6) and glycoprotein 130 (gp130) receptors signaling have established roles in some types of cancer-induced muscle wasting through disruptions to protein turnover and oxidative capacity. Although exercise has documented benefits for cancer prevention and patient survival, there are significant gaps in our understanding of muscle adaptation and plasticity during severe cachexia. Preclinical models have provided valuable insight into the adaptive potential of muscle contraction within the cancer environment. We summarize the current understanding of how resistance-type exercise impacts mechanisms involved in cancer-induced muscle atrophy and dysfunction. Specifically, the role of IL-6 and gp130 receptors in the pathophysiology of muscle wasting and the adaptive response to exercise is explained. The discussion includes current knowledge gaps and future research directions needed to improve preclinical research and accelerate clinical translation in human patients with cancer.

Effects of 6-(Methylsulfinyl)hexyl Isothiocyanate Ingestion on Muscle Damage after Eccentric Exercise in Healthy Males: A Pilot Placebo-Controlled Double-Blind Crossover Study.

An animal study demonstrated that 6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC), a major bioactive compound in Japanese pungent spice wasabi, has an action of inhibiting the activation of calpain-1 (a protease). Increases in calpain activity can cause continual strength loss after eccentric exercise. It remains to be determined in humans whether 6-MSITC intake would modulate calpain and/or muscle damage responses after eccentric exercise. We performed a randomized, double-blind, crossover design study wherein eight healthy young males were randomly assigned to ingest 9 mg/day of 6-MSITC or placebo from 1 day before exercise to 4 days after exercise (30 maximal isokinetic eccentric contractions of the elbow flexors using an isokinetic dynamometer). Calpain-1 concentration, inflammatory and muscle damage markers (creatine kinase activity, urinary titin concentration, muscle strength, range of motion, muscle soreness and transverse relaxation time) were assessed. Plasma calpain-1 concentration after eccentric exercise was similar between the placebo- and 6-MSITC-treated conditions. All muscle damage and inflammatory markers were not affected by 6-MSITC relative to those in the placebo-treated condition. Our results suggest that 6-MSITC has no effect on plasma calpain-1 concentration and muscle damage and inflammatory markers measured after eccentric exercise.

Contraction-Induced Loss of Plasmalemmal Electrophysiological Function Is Dependent on the Dystrophin Glycoprotein Complex.

Weakness and atrophy are key features of Duchenne muscular dystrophy (DMD). Dystrophin is one of the many proteins within the dystrophin glycoprotein complex (DGC) that maintains plasmalemmal integrity and cellular homeostasis. The dystrophin-deficient mdx mouse is also predisposed to weakness, particularly when subjected to eccentric (ECC) contractions due to electrophysiological dysfunction of the plasmalemma. Here, we determined if maintenance of plasmalemmal excitability during and after a bout of ECC contractions is dependent on intact and functional DGCs rather than, solely, dystrophin expression. Wild-type (WT) and dystrophic mice (mdx, mL172H and Sgcb-/- mimicking Duchenne, Becker and Limb-girdle Type 2E muscular dystrophies, respectively) with varying levels of dystrophin and DGC functionality performed 50 maximal ECC contractions with simultaneous torque and electromyographic measurements (M-wave root-mean-square, M-wave RMS). ECC contractions caused all mouse lines to lose torque (p<0.001); however, deficits were greater in dystrophic mouse lines compared to WT mice (p<0.001). Loss of ECC torque did not correspond to a reduction in M-wave RMS in WT mice (p=0.080), while deficits in M-wave RMS exceeded 50% in all dystrophic mouse lines (p≤0.007). Moreover, reductions in ECC torque and M-wave RMS were greater in mdx mice compared to mL172H mice (p≤0.042). No differences were observed between mdx and Sgcb-/- mice (p≥0.337). Regression analysis revealed ≥98% of the variance in ECC torque loss could be explained by the variance in M-wave RMS in dystrophic mouse lines (p<0.001) but not within WT mice (R 2=0.211; p=0.155). By comparing mouse lines that had varying amounts and functionality of dystrophin and other DGC proteins, we observed that (1) when all DGCs are intact, plasmalemmal action potential generation and conduction is maintained, (2) deficiency of the DGC protein ß-sarcoglycan is as disruptive to plasmalemmal excitability as is dystrophin deficiency and, (3) some functionally intact DGCs are better than none. Our results highlight the significant role of the DGC plays in maintaining plasmalemmal excitability and that a collective synergism (via each DGC protein) is required for this complex to function properly during ECC contractions.

Preconditioning contractions prevent prolonged force depression and Ca2+-dependent proteolysis of STAC3 after damaging eccentric contractions.

Preconditioning contractions (PCs) have been shown to markedly improve recovery from eccentric contractions (ECCs)-induced force depression. We here examined the mechanism behind the effects of PCs with focusing on the SH3 and cysteine-rich domain 3 (STAC3) that is essential for coupling membrane depolarization to Ca2+ release from the sarcoplasmic reticulum. Rat medial gastrocnemius (MG) muscles were excised immediately (REC0), 1 day (REC1), and 4 days (REC4) after exposure to 100 repeated damaging ECCs in vivo. PCs with 10 repeated nondamaging ECCs were applied 2 days before the damaging ECCs. Damaging ECCs induced in vivo isometric torque depression at 50 and 100 Hz stimulation frequencies, which was accompanied by a significant decrease in the amount of full-length STAC3, an activation of calpain 1, and an increased number of Evans Blue dye-positive fibers in MG muscles at REC1 and REC4. Interestingly, PCs attenuated all these deleterious alterations induced by damaging ECCs. Moreover, mechanistic experiments performed on normal muscle samples exposed to various concentration of Ca2+ showed a Ca2+-dependent proteolysis of STAC3, which was prevented by calpain inhibitor MDL-28170. In conclusion, PCs may improve recovery from force depression after damaging ECCs, in part by inhibiting the loss of STAC3 due to the increased permeability of cell membrane and subsequent activation of calpain 1.NEW & NOTEWORTHY The SH3 and cysteine-rich domain 3 (STAC3) is a skeletal muscle-specific protein that couples membrane depolarization to sarcoplasmic reticulum Ca2+ release. No studies, however, examined the role of STAC3 in protective effects of preconditioning contractions (PCs) against damaging eccentric contractions (ECCs). Here, we demonstrate that PCs may improve recovery from damaging ECCs-induced force depression, in part by an inhibition of Ca2+-dependent proteolysis of STAC3 due to increased membrane permeability and subsequent calpain 1 activation.

Maximal results with minimal stimuli: the fewest high-frequency pulses needed to measure or model prolonged low-frequency force depression in the dorsiflexors.

Quantifying prolonged low-frequency force depression (PLFFD) with the gold-standard 1-s trains presents challenges, so paired pulses have been used. Owing to greater impairment of high-frequency doublet than tetanic torque, paired pulses underestimate PLFFD. This study aimed to approximate the minimum number of high-frequency pulses needed to avoid such underestimation and assess the feasibility of modeling PLFFD from a limited number of experimental pulses. In 13 participants, a 1-s 10-Hz train and 100-Hz trains with 2, 4, 7, 12, 15, 25, 50, or 100 pulses were evoked before and after (15 min, 2, 4, and 7 days) eccentric exercise of the dorsiflexors. With ≤12 pulses, impairment of 100-Hz torque was greater than the 1-s train (P ≤ 0.05; e.g., 12 vs. 100 pulses at 4 days: 97.8 ± 8.5% vs. 100.5 ± 8.2% baseline). Consequently, with ≤12 pulses, PLFFD was underestimated compared with the gold-standard measure (P ≤ 0.05; e.g., 12 vs. 100 pulse 10:100-Hz torque ratio at 4 days: 86.8 ± 12.8% vs. 84.6 ± 13.5% baseline). Modeling reproduced 10:100-Hz ratios (PLFFD) with 95% limits of agreement of -13.6% to 16.7% of experimental values with ≥12 pulses. Our results indicate that a minimum of 13-25 pulses of 100 Hz are needed to accurately quantify PLFFD in the dorsiflexors. Although this may not be the minimum range for other muscles, a similar relationship with pulse number likely exists. Modeling may eventually provide an option to estimate PLFFD from experimental trains with relatively few pulses; however, further development is imperative to reduce variability.NEW & NOTEWORTHY Ideally, prolonged low-frequency force depression (PLFFD) is measured with 1-s trains of supramaximal stimuli; however, this induces considerable discomfort. We tested briefer trains to approximate the minimum number of high-frequency pulses needed to accurately determine PLFFD and the feasibility of modeling 1-s tetani with relatively few pulses. After eccentric exercise, 13-25 high-frequency pulses were needed to accurately measure PLFFD. Modeling reproduced mean experimental values but had considerable variability.

Power Amplification Increases With Contraction Velocity During Stretch-Shortening Cycles of Skinned Muscle Fibers.

Muscle force, work, and power output during concentric contractions (active muscle shortening) are increased immediately following an eccentric contraction (active muscle lengthening). This increase in performance is known as the stretch-shortening cycle (SSC)-effect. Recent findings demonstrate that the SSC-effect is present in the sarcomere itself. More recently, it has been suggested that cross-bridge (XB) kinetics and non-cross-bridge (non-XB) structures (e.g., titin and nebulin) contribute to the SSC-effect. As XBs and non-XB structures are characterized by a velocity dependence, we investigated the impact of stretch-shortening velocity on the SSC-effect. Accordingly, we performed in vitro isovelocity ramp experiments with varying ramp velocities (30, 60, and 85% of maximum contraction velocity for both stretch and shortening) and constant stretch-shortening magnitudes (17% of the optimum sarcomere length) using single skinned fibers of rat soleus muscles. The different contributions of XB and non-XB structures to force production were identified using the XB-inhibitor Blebbistatin. We show that (i) the SSC-effect is velocity-dependent-since the power output increases with increasing SSC-velocity. (ii) The energy recovery (ratio of elastic energy storage and release in the SSC) is higher in the Blebbistatin condition compared with the control condition. The stored and released energy in the Blebbistatin condition can be explained by the viscoelastic properties of the non-XB structure titin. Consequently, our experimental findings suggest that the energy stored in titin during the eccentric phase contributes to the SSC-effect in a velocity-dependent manner.

A below-knee compression garment reduces fatigue-induced strength loss but not knee joint position sense errors.

PURPOSE: We examined the possibility that wearing a below-knee compression garment (CG) reduces fatigue-induced strength loss and joint position sense (JPS) errors in healthy adults. METHODS: Subjects (n = 24, age = 25.5 ± 4 years) were allocated to either one of the treatment groups that performed 100 maximal isokinetic eccentric contractions at 30°-1 with the right-dominant knee extensors: (1) with (EXPCG) or (2) without CG (EXP) or to (3) a control group (CONCG: CG, no exercise). Changes in JPS errors, and maximal voluntary isometric contraction (MVIC) torque were measured immediately post-, 24 h post-, and 1 week post-intervention in each leg. All testing was done without the CG. RESULTS: CG afforded no protection against JPS errors. Mixed analysis of variance (ANOVA) revealed that absolute JPS errors increased post-intervention in EXPCG and EXP not only in the right-exercised (52%, p = 0.013; 57%, p = 0.007, respectively) but also in the left non-exercised (55%, p = 0.001; 58%, p = 0.040, respectively) leg. Subjects tended to underestimate the target position more in the flexed vs. extended knee positions (75-61°: - 4.6 ± 3.6°, 60-50°: - 4.2 ± 4.3°, 50-25°: - 2.9 ± 4.2°), irrespective of group and time. Moreover, MVIC decreased in EXP but not in EXPCG and CONCG at immediately post-intervention (p = 0.026, d = 0.52) and 24 h post-intervention (p = 0.013, d = 0.45) compared to baseline. CONCLUSION: Altogether, a below-knee CG reduced fatigue-induced strength loss at 80° knee joint position but not JPS errors in healthy younger adults.

Effects of deceleration-focused exercise strategies on shoulder range of motion and throwing velocity in baseball and softball athletes.

This study examined the effects of deceleration-focused exercises on shoulder range of motion and throwing velocity in both softball and baseball players. Volunteers included 28 Division III William Paterson University baseball and softball athletes (18 females and 10 males), who were evenly distributed across two groups both undertaking 14 sessions of either resistance band or handheld medicine ball exercises (band vs. ball group). A pre-test and post-test measured participants' best active internal/external shoulder rotation and best throwing velocity at a target 40 ft away. A two-tailed, independent t-test showed no significant differences in velocity, internal rotation or external rotation (p < 0.01) between the band and ball groups. However, the average change in velocity in the ball group was double that of the band group (1.50 ± 2.06 m/s versus 0.73 ± 2.24 m/s). For change in both internal and external rotation the band group (2.86 ± 5.27° and 3.29 ± 3.87°, respectively) was greater than the ball mean (1.93° ± 3.32° and 1.29 ± 6.52°, respectively). These findings suggest that overhead athletes aiming to increase throwing velocity can benefit from performing deceleration training with weighted balls whereas resistance bands appear to improve shoulder rotation.

Changes in supramaximal M-wave amplitude at different regions of biceps brachii following eccentric exercise of the elbow flexors.

PURPOSE: Previous evidence from surface electromyograms (EMGs) suggests that exercise-induced muscle damage (EIMD) may manifest unevenly within the muscle. Here we investigated whether these regional changes were indeed associated with EIMD or if they were attributed to spurious factors often affecting EMGs. METHODS: Ten healthy male subjects performed 3 × 10 eccentric elbow flexions. Maximal voluntary contraction (MVC), muscle soreness and ultrasound images from biceps brachii distal and proximal regions were measured immediately before (baseline) and during each of the following 4 days after the exercise. Moreover, 64 monopolar surface EMGs were detected while 10 supramaximal pulses were applied to the musculocutaneous nerve. The innervation zone (IZ), the number of electrodes detecting largest M-waves and their centroid longitudinal coordinates were assessed to characterize the spatial distribution of the M-waves amplitude. RESULTS: The MVC torque decreased (~ 25%; P < 0.001) while the perceived muscle soreness scale increased (~ 4 cm; 0 cm for no soreness and 10 cm for highest imaginable soreness; P < 0.005) across days. The echo intensity of the ultrasound images increased at 48 h (71%), 72 h (95%) and 96 h (112%) for both muscle regions (P < 0.005), while no differences between regions were observed (P = 0.136). The IZ location did not change (P = 0.283). The number of channels detecting the greatest M-waves significantly decreased (up to 10.7%; P < 0.027) and the centroid longitudinal coordinate shifted distally at 24, 48 and 72 h after EIMD (P < 0.041). CONCLUSION: EIMD consistently changed supramaximal M-waves that were detected mainly proximally from the biceps brachii, suggesting that EIMD takes place locally within the biceps brachii.

Effect of preconditioning exercise on biceps brachii myotendinous junction displacement during elbow flexor eccentric exercise.

The present study tested the hypothesis that 30 low-intensity (10%) eccentric contractions (10%EC) or two maximal voluntary isometric contractions at a long muscle length (2MVIC) that were performed at two days before maximal eccentric exercise of the elbow flexors consisting of five sets of six maximal eccentric contractions (MaxEC) would reduce increases in biceps brachii distal myotendinous junction displacement (MTJd) over the eccentric contractions during MaxEC. Sedentary young men were randomly placed (n = 12/group) to a control group that performed two bouts of MaxEC (CONT-1st, CONT-2nd) separated by two weeks, or one of two preconditioning groups that performed 10%EC or 2MVIC at 20° elbow flexion at two days prior to MaxEC. All exercises were performed by the non-dominant arm. MTJd of each contraction was assessed by B-mode ultrasound, and its changes over sets were compared among the groups. The average MTJd from the start to the end of six eccentric contractions in the first set was similar among the groups (6.4 ± 0.7 mm). The MTJd increased from the first to fifth set, but the increase was smaller (P < .05) for the 10%EC (13 ± 6%) and 2MVIC (16 ± 9%) groups, and CONT-2nd (3 ± 6%) when compared with CONT-1st (60 ± 12%). Both 10%EC and 2MVIC groups showed smaller (P < .05) changes in all muscle damage markers after MaxEC similarly when compared with CONT-1st, but the changes were greater than those after CONT-2nd. These results supported the hypothesis that protective effect was associated with less MTJd changes, suggesting that this is associated with the mechanisms underpinning the preconditioning effect on muscle damage.

Repeated eccentric contractions positively regulate muscle oxidative metabolism and protein synthesis during cancer cachexia in mice.

Cancer-induced wasting is accompanied by disruptions to muscle oxidative metabolism and protein turnover that have been associated with systemic inflammation, whereas exercise and stimulated muscle contractions can positively regulate muscle protein synthesis and mitochondrial homeostasis. In preclinical cancer cachexia models, a single bout of eccentric contractions (ECCs) can induce protein synthesis and repeated ECC bouts prevent myofiber atrophy. The cellular mechanisms providing this protection from atrophy have not been resolved. Therefore, the purpose of this study was to determine whether repeated stimulated ECC bouts affect basal muscle oxidative metabolism and protein synthesis during cancer cachexia, and if these changes were associated with plasma IL-6 levels. Male ApcMin/+ (MIN; n = 10) mice initiating cachexia and healthy C57BL/6 (B6; n = 11) control mice performed repeated ECC bouts over 2 wk. MIN mice exhibited body weight loss and elevated plasma IL-6 before and during repeated ECC bouts. Control MIN muscle demonstrated disrupted signaling related to inflammation, oxidative capacity, and protein synthesis regulation, which were all improved by repeated ECC bouts. With cachexia, plasma IL-6 levels were negatively correlated with myofiber cross-sectional area, oxidative capacity, and protein synthesis. Interestingly, ECC improvements in these outcomes were positively correlated with plasma IL-6 levels in MIN mice. There was also a positive relationship between muscle oxidative capacity and protein synthesis after repeated ECC bouts in MIN mice. Collectively, repeated ECC bouts altered the cachectic muscle phenotype independent of systemic wasting, and there was a strong association between muscle oxidative capacity and protein synthesis in this adaptive response.NEW & NOTEWORTHY Cancer-induced muscle wasting is accompanied by disruptions to muscle oxidative metabolism and protein turnover regulation, whereas exercise is a potent stimulator of muscle protein synthesis and mitochondrial homeostasis. In a preclinical model of cancer cachexia, we report that cachectic muscle retains anabolic and metabolic plasticity to repeated eccentric contraction bouts despite an overall systemic wasting environment. The attenuation of muscle atrophy is linked to improved oxidative capacity and protein synthesis during cancer cachexia progression.

Compound maximal motor unit response is modulated by contraction intensity, but not contraction type in tibialis anterior.

Determining a single compound maximal motor response (MMAX ) or an average superimposed MMAX response (MSUP ) are commonly used reference values in experiments eliciting raw electromyographic, motor evoked potentials, H-reflexes, and V-waves. However, existing literature is limited in detailing the most appropriate method to normalize these electrophysiological measures. Due to the accessibility of assessment from a cortical and spinal perspective, the tibialis anterior is increasingly used in literature and hence investigated in this study. The aims of the present study were to examine the differences and level of agreement in MMAX /MSUP under different muscle actions and contraction intensities. Following a familiarization session, 22 males visited the laboratory on a single occasion. MMAX was recorded under 10% isometric and 25% and 100% shortening and lengthening maximal voluntary contractions (MVC) at an angular velocity of 15° sec-1 . MSUP was also recorded during 100% shortening and lengthening with an average of five responses recorded. There were no differences in MMAX or MSUP between contraction types. All variables showed large, positive correlations (P < 0.001, r2  ≥ 0.64). MMAX amplitude was larger (P < 0.001) at 100% shortening and lengthening intensity compared to MMAX amplitude at 10% isometric and 25% lengthening MVC. Bland-Altman plots revealed a bias toward higher MMAX at the higher contraction intensities. Despite MSUP being significantly smaller than MMAX (P < 0.001) at 100% MVC, MSUP showed a large positive correlation (P < 0.001, r2  ≥ 0.64) with all variables. It is our recommendation that MMAX should be recorded at specific contraction intensity but not necessarily a specific contraction type.

What is the level of dystrophin expression required for effective therapy of Duchenne muscular dystrophy?

Duchenne muscular dystrophy (DMD) is a fatal X-linked muscle wasting disease. The disease is due to mutations in the DMD gene that encodes for a large intracellular protein called dystrophin. Dystrophin plays a critical role in linking the internal cytoskeleton of the striated muscle cell with the extracellular matrix as well as having cell signalling functions. In its absence muscle contraction is associated with cycles of damage, repair, inflammation and fibrosis with eventual loss of muscle and replacement with fat. Experiments in animal models of DMD have generated a number of different approaches to the induction of dystrophin including viral vector mediated delivery of a recombinant dystrophin gene, antisense oligonucleotide mediated exon-skipping to restore the open reading frame in the dystrophin mRNA, read-through of premature stop mutations, genome modification using CRISPR-Cas9 or cell based transfer of a functional dystrophin gene. In all cases, it will be important to understand how much dystrophin expression is required for a clinically effective therapy and this review examines the data from humans and animal models to estimate the percentage of endogenous dystrophin that is likely to have significant clinical benefit. While there are a number of important caveats to consider, including the appropriate outcome measures, this review suggests that approximately 20% of endogenous levels uniformly distributed within the skeletal muscles and the heart may be sufficient to largely prevent disease progression.

Non-Uniformity of Elbow Flexors Damage Induced by an Eccentric Protocol in Untrained Men.

Muscle structure disorganization is a consequence of intense eccentric contractions, with symptoms that characterize exercise-induced muscle damage (EIMD). To date, few studies have described EIMD parameters at different muscle sites. The aim of the present study was to analyse indirect markers of EIMD at two elbow flexors sites over three days. Eleven healthy untrained men were submitted to a session of three sets of 10 eccentric elbow flexion repetitions on an isokinetic dynamometer. The isometric peak torque (PT), muscle soreness, elbow flexors oedema, (normalized muscle thickness [MT]) and echo-intensity (EI) were measured. There was a significant decrease in PT immediately after (Post) and 10 min, 24 h, 48 h and 72 h after intervention compared to that at baseline (p < 0 .05). MT% increased after 72 h compared with that immediately, 10 min and 24 h after intervention (p < 0.05). No statistical changes were observed in muscle soreness and oedema between the two muscle sites. With respect to EI%, significant differences were observed for the 24 h, 48 h and 72 h measures compared with those of the Post, 10 min and 24 h measures for both muscle sites; at the distal site, EI% was significantly higher than at the proximal site for measures after 24 h (p < 0.05). The presence of differences in EI% 24 h after eccentric training on distal sites of elbow flexors indicates non-uniform EIMD in this region.