Quantitative and qualitative adaptations of muscle fibers to glucocorticoids

Introduction: The aim of this study was to understand the effects of short‐term glucocorticoid administration in healthy subjects. Methods: Five healthy men received dexamethasone (8 mg/day) for 7 days. Vastus lateralis muscle biopsy and knee extension torque measurement were performed before and after administration. A large number of individual muscle fibers were dissected from the biopsy samples (pre‐administration: n = 165, post‐administration: n = 177). Results: Maximal knee extension torque increased after administration (～13%), whereas both type 1 and type 2A fibers had decreased cross‐sectional area (type 1: ～11%, type 2A: ～17%), myosin loss (type 1: ～18%, type 2A: ～32%), and loss of specific force (type 1: ～24%, type 2A: ～33%), which were preferential for fast fibers. Conclusion: Short‐term dexamethasone administration in healthy subjects elicits quantitative and qualitative adaptations of muscle fibers that precede (and may predict) the clinical appearance of myopathy in glucocorticoid‐treated subjects. Muscle Nerve 52: 631–639, 2015     

Effect of recombinant human MG53 protein on tourniquet‐induced ischemia‐reperfusion injury in rat muscle

Introduction: Skeletal muscle ischemia–reperfusion injury (I‐R) is a complex injury process that includes damage to the sarcolemmal membrane, contributing to necrosis and apoptosis. MG53, a muscle‐specific TRIM family protein, has been shown to be essential for regulating membrane repair and has been shown to be protective against cardiac I‐R and various forms of skeletal muscle injury. The purpose of this study was to determine if recombinant human MG53 (rhMG53) administration offered protection against I‐R. Methods: rhMG53 was administered to rats immediately before tourniquet‐induced ischemia and again immediately before reperfusion. Two days later muscle damage was assessed histologically. Results: rhMG53 offered no protective effect, as evidenced primarily by similar Evans blue dye inclusion in the muscles of rats administered rhMG53 or saline. Conclusions: Administration of rhMG53 does not offer protection against I‐R in rat skeletal muscle. Additional studies are required to determine if the lack of a response is species‐specific. Muscle Nerve 49 : 919–921, 2014     

Voluntary rate of torque development is impaired after a voluntary versus tetanic conditioning contraction

Introduction: Both voluntary and evoked conditioning contractions will potentiate muscle twitch contractile properties. The response of a voluntary contraction to each condition type is not well understood but it may be a more functional model than evoked twitch potentiation. Methods: Baseline measurements from tibialis anterior included: maximal isometric twitch torque and rate of torque development (RTD); maximal evoked 50‐Hz torque; and maximal voluntary ballistic RTD. Potentiation was induced by a 10‐s voluntary or tetanic contraction (∽78% MVC), followed by 2 twitches and 2 ballistic contractions. Results: Twitch properties (torque and RTD) were potentiated equally after each conditioning contraction. Ballistic RTD was greater post‐tetanus (390.2 ± 59.3 Nm/s) than post‐voluntary (356.4 ± 69.1 Nm/s), but both were reduced from baseline (422.0 ± 88.9 Nm/s). Conclusions: Twitch potentiation was similar between conditioning contraction types, but ballistic RTD was lower after post‐tetanus than post‐voluntary. The results indicate central inhibition or fatigue concurrent with peripheral potentiation. Muscle Nerve 49 : 218–224, 2014     

Neuromuscular fatigue after low‐ and medium‐frequency electrical stimulation in healthy adults

Introduction: In this study we investigated fatigue origins induced by low‐frequency pulsed current (PC) and medium‐frequency current (MF) neuromuscular electrical stimulation (NMES) after a clinical‐like session. Methods: Eleven healthy men randomly underwent 2 NMES sessions, PC and MF, on quadriceps muscle (15‐minute duration, 6 seconds on and 18 seconds off). Maximal voluntary contraction (MVC), central activation ratio (CAR), vastus lateralis electromyographic activity (EMG), and evoked contractile properties were determined before and after the sessions. Evoked torque and discomfort during the sessions were also measured. Results: Both currents produced decreases in MVC, EMG, and evoked contractile properties after the sessions. No difference was found between currents for all variables (P > 0.05). Evoked torque during sessions decreased (P < 0.05). No difference was observed in mean evoked torque and discomfort (P > 0.05). Discussion: Both currents induced similar neuromuscular fatigue. Clinicians can choose either PC or MF and expect similar treatment effects when the goal is to generate gains in muscle strength. Muscle Nerve 58 : 293–299, 2018     

Statin-associated changes in skeletal muscle function and stress response after novel or accustomed exercise

Introduction: The most common side effect of statins, myopathy, is more likely in exercisers. We investigated the interaction of statin treatment with novel vs. accustomed exercise on muscle function, heat shock protein (Hsp) expression, and caspase activation. Methods: Mice received daily cerivastatin or saline for 2 weeks, with/without wheel running (RW) (novel/sedentary). Accustomed groups completed 2 weeks of RW before statins. At 4 weeks, plantarflexor isometric force, Hsp25, αB‐crystallin, caspase‐3 and ‐9, and plasma creatine kinase (CK) were quantified. Results: Statins reduced force in sedentary and novel groups, compared with saline, by 15% and 27%, respectively. Muscle fatigability increased 21% and 30% with statins compared with saline in sedentary and novel groups, respectively. Accustomed exercise prevented statin‐associated force loss and increased fatigability. CK did not correlate with functional outcomes. RW increased Hsp protein in all groups. Conclusion: Our results suggest that exercise prior to statin treatment can protect against decrements in muscle function. Muscle Nerve 2011     

Echo intensity independently predicts functionality in sedentary older men

Introduction: The aim of this study was to examine the associations between quadriceps muscle functionality features in nonactive older men to determine predictors of functional performance. Methods: Quadriceps functional parameters, including quadriceps echo intensity (QEI), rate of torque development (RTD), and the 30 s sit‐to‐stand test (30SS), were assessed in 50 healthy sedentary older men (66 ± 5.4 years). RTD/QEI ratios were also calculated to identify the best predictor of functional performance. Results: 30SS performance was associated with RTD, muscle thickness, RTD‐50/QEI, RTD‐100/QEI, RTD‐50/QEI/WBM, and RTD‐100/QEI/WBM. A multiple stepwise linear regression demonstrated that QEI was the best single predictor of functional performance, explaining ～30% of the 30SS variance. Conclusions: These results indicate that QEI was the strongest contributor to functionality of nonactive older men, suggesting that QEI may be an alternative tool for screening of muscle impairment that leads to decreased functional performance in this population. Muscle Nerve 55 : 9–15, 2017     

Physical exercise during muscle regeneration improves recovery of the slow/oxidative phenotype

Introduction: As skeletal muscle mass recovery after extensive injury is improved by contractile activity, we explored whether concomitant exercise accelerates recovery of the contractile and metabolic phenotypes after muscle injury. Methods: After notexin‐induced degeneration of a soleus muscle, Wistar rats were assigned to active (running exercise) or sedentary groups. Myosin heavy chains (MHC), metabolic enzymes, and calcineurin were studied during muscle regeneration at different time points. Results: The mature MHC profile recovered earlier in active rats (21 days after injury) than in sedentary rats (42 days). Calcineurin was higher in the active degenerated than in the sedentary degenerated muscles at day 14. Citrate synthase and total lactate dehydrogenase (LDH) activity decreased after injury and were similarly recovered in both active and sedentary groups at 14 or 42 days, respectively. H‐LDH isozyme activity recovered earlier in the active rats. Conclusions: Exercise improved recovery of the slow/oxidative phenotype after soleus muscle injury. Muscle Nerve 55 : 91–100, 2017     

Effects of moderate‐ and high‐intensity chronic exercise on brain‐derived neurotrophic factor expression in fast and slow muscles

Introduction: Brain‐derived neurotrophic factor (BDNF) protein expression is sensitive to cellular activity. In the sedentary state, BDNF expression is affected by the muscle phenotype. Methods: Eighteen Wistar rats were divided into the following 3 groups: sedentary (S); moderate‐intensity training (MIT); and high‐intensity training (HIT). The training protocol lasted 8 weeks. Forty‐eight hours after training, total RNA and protein levels in the soleus and plantaris muscles were obtained. Results: In the plantaris, the BDNF protein level was lower in the HIT than in the S group (P < 0.05). A similar effect was found in the soleus (without significant difference). In the soleus, higher Bdnf mRNA levels were found in the HIT group (P < 0.001 vs. S and MIT groups). In the plantaris muscle, similar Bdnf mRNA levels were found in all groups. Conclusions: These results indicate that high‐intensity chronic exercise reduces BDNF protein level in fast muscles and increases Bdnf mRNA levels in slow muscles. Muscle Nerve 53: 446–451, 2016     

Muscle function in A canine model of X‐linked myotubular myopathy

Introduction: We established a colony of dogs that harbor an X‐linked MTM1 missense mutation.Muscle from affected male dogs exhibits reduction and altered localization of the MTM1 gene product, myotubularin, and provides a model analogous to X‐linked myotubular myopathy (XLMTM). Methods: We studied hindlimb muscle function in age‐matched canine XLMTM genotypes between ages 9 and 18 weeks. Results: By the end of the study, affected dogs produce only ～15% of the torque generated by normals or carriers (0.023 ± 0.005 vs. 0.152 ± 0.007 and 0.154 ± 0.003 N‐m/kg body mass, respectively, P < 0.05) and are too weak to stand unassisted. At this age, XLMTM dogs also demonstrate an abnormally low twitch:tetanus ratio, a right‐shifted torque‐frequency relationship and an increase in torque during repetitive stimulation (P < 0.05). Conclusions: We hypothesize that muscle weakness results from impaired excitation‐contraction (E‐C) coupling. Interventions that improve E‐C coupling might be translated from the XLMTM dog model to patients. Muscle Nerve 46: 588–591, 2012     

Low‐intensity running exercise enhances the capillary volume and pro‐angiogenic factors in the soleus muscle of type 2 diabetic rats

Introduction: We determined the effects of low‐intensity exercise on the three‐dimensional capillary structure and associated angiogenic factors in the soleus muscle of Goto‐Kakizaki (GK) diabetic rats. Methods: Four groups of male rats were studied: sedentary nondiabetic (Con), exercised nondiabetic control (Ex), sedentary GK, and exercised GK (GK+Ex). Rats in the Ex and GK+Ex groups were subjected to chronic low‐intensity running on a treadmill (15 m/min, 60 min/session, 5 sessions/week for 3 weeks). Results: Although mean capillary volume and diameter were lower in the GK compared with all other groups, low‐intensity exercise increased both of these measures in GK rats. Mitochondrial markers, i.e., SDH activity and PGC‐1α expression, and the levels of angiogenic factors were higher in the GK+Ex than all other groups. Exercise increased vascular endothelial growth factor (VEGF) protein levels and the VEGF‐to‐TSP‐1 ratio, an indicator of angiogenesis, in GK rats. Conclusions: Combined, the results indicate that low‐intensity exercise reduces some of the microcirculatory complications in type 2 diabetic muscles. Muscle Nerve 51: 391–399, 2015     

Amelioration of ischemia‐reperfusion–induced muscle injury by the recombinant human MG53 protein

Introduction: Ischemia‐reperfusion injury (I‐R) in skeletal muscle requires timely treatment. Methods: Rodent models of I‐R injury were used to test the efficacy of recombinant human MG53 (rhMG53) protein for protecting skeletal muscle. Results: In a mouse I‐R injury model, we found that mg53,?/? mice are more susceptible to I‐R injury. rhMG53 applied intravenously to the wild‐type mice protected I‐R injured muscle, as demonstrated by reduced CK release and Evans blue staining. Histochemical studies confirmed beneficial effects of rhMG53. Of interest, rhMG53 did not protect against I‐R injury in rat skeletal muscle. This was likely due to the fact that the plasma level of endogenous MG53 protein is high in rats. Conclusions: Our data suggest that rhMG53 may be a potential therapy for protection against muscle trauma. A mouse model appears to be a better choice than a rat model for evaluating potential treatments for protecting skeletal muscle. Muscle Nerve 52 : 852–858, 2015     

Assessment of rat sciatic nerve function following acute implantation of high density utah slanted electrode array (25 electrodes/mm2) based on neural recordings and evoked muscle activity

Introduction: High density Utah slanted electrode arrays (HD‐USEAs) have been developed recently for intrafascicular access to submillimeter neural structures. Insertion of such high electrode density devices may cause nerve crush injury, counteracting the intended improved selective nerve fiber access. Methods: HD‐USEAs were implanted into sciatic nerves of anesthetized rats. Nerve function was assessed before and after HD‐USEA implantation by measuring changes in evoked muscle and nerve compound action potentials and single unit neuronal recordings. Results: Neural activity was recorded with over half of all implanted electrodes. Average decreases of 38%, 36%, and 13% in nerve, medial gastrocnemius, and tibialis anterior compound action potential amplitudes, respectively, were observed following array implantation. Only 1 of 8 implantations resulted in loss of all signals. Conclusions: These studies demonstrate that HD‐USEAs provide a useful neural interface without causing a nerve crush injury that would otherwise negate their use in acute preparations (<12 h). Muscle Nerve 50 : 417–424, 2014     

Comparison between the effects of 4 different electrical stimulation current waveforms on isometric knee extension torque and perceived discomfort in healthy women

Introduction: We studied the effects of different neuromuscular electrical stimulation (NMES) currents, 2 kHz‐frequency alternating currents (KACs, Russian and Aussie) and 2 pulsed currents (PCs), on isometric knee extension torque and discomfort level, both in isolation and combined, with maximum voluntary contraction (MVC). Methods: Twenty‐one women (age 21.6 ± 2.5 years) were studied. We evaluated torque evoked by NMES or NMES combined with maximum voluntary contraction of the quadriceps muscle of healthy women. Discomfort level was measured using a visual analog pain scale. Results: Despite comparable levels of discomfort, evoked torque was lower for Russian current compared with the other modalities (Russian 50.8%, Aussie 71.7%, PC500 76.9%, and PC200 70.1%; P < 0.001). There was no advantage in combining NMES with MVC compared with isolated NMES. Conclusions: The Aussie and PC approaches proved superior to Russian current for inducing isometric knee extension torque. This information is important in guiding decision making with regard to NMES protocols for muscle strengthening. Muscle Nerve 51 : 76–82, 2015     

Soleus H‐reflex modulation during balance recovery after forward falling

Introduction: Our purpose was to examine the Hoffmann reflex (H‐reflex) during balance recovery after a simulated forward fall from 2 different inclination angles. Methods: The soleus H‐reflex of 15 healthy adults was measured in 2 different leaning positions (exerting a horizontal force at 15% and 30% of body weight, respectively), with no release (Int0) and at 2 different intervals (Int1, Int2) after the release (～45 and ～65 ms, respectively). Results: During Int2, the H‐reflex, which was evoked before the onset of the soleus electromyography, was significantly higher than the H‐reflex induced 20 ms earlier (Int1). No significant difference was observed between Int0 and Int1 and between the 2 leaning positions. Conclusions: These findings indicate that Ia afferent input is facilitated before muscle activation during forward falling. This could be important for the timely activation and increased rate of force development required during this task. Muscle Nerve 54 : 952–958, 2016     

Selectively reshaping a muscle phenotype: functional overload of cat plantaris

Introduction: Functional overload (FO) of the fast plantaris muscle was studied in treadmill‐exercised (FO‐Ex) or sedentary (FO‐Sed) adult cats. Methods: Mechanical, phenotype, and kinematics analyses were performed. Results: Plantigrade vs. normal digitigrade posture was observed early post‐FO. Relative plantaris mass was greater in FO‐Sed (10%) and FO‐Ex (60%) cats than in controls 12 weeks post‐FO. Specific tension was similar across groups, indicating functional hypertrophy. Fiber size was greater, percent slow fibers higher, percent IIa myosin heavy chain (MHC) higher, and IIx MHC lower in FO‐Ex than controls. Twitch and half‐relaxation times were longer, and the frequency–tension curve shifted toward that observed in slow muscles. Electromyography (EMG) and tendon force amplitudes during stepping were larger, and the yield (lengthening) phase occurred at a longer muscle length before compared with after FO. Discussion: Reshaping the plantaris phenotype was highly dependent on the overload stimulus, indicating that electrical stimulation paradigms used during rehabilitation should be performed with the muscles under “loaded” conditions. Muscle Nerve, 2011     

An internet‐based physical activity intervention for adolescents with cerebral palsy: a randomized controlled trial

Aim To determine the effectiveness of an 8‐week internet‐based, lifestyle physical‐activity intervention for adolescents with cerebral palsy (CP). Method A randomized controlled trial using concealed allocation with blinded assessments at baseline, 10, and 20 weeks. Forty‐one adolescents with CP participated (26 males, 15 females; mean age 13y 7mo, SD 1y 8mo, range 11–17y; Gross Motor Function Classification System levels: I, n=21; II, n=17; III, n=3; unilateral distribution n=16, bilateral n=25). Primary outcome was physical activity (NL‐1000 accelerometers and self‐report [Multimedia Activity Recall for Children and Adolescents: MARCA]). Secondary outcomes were exercise knowledge (a purpose‐designed scale), attitudes, intention and self‐efficacy (Lifestyle Education for Activity Program II scales), self‐reported sedentary behaviour (MARCA), and functional capacity (6‐min walk test). Results At 10 weeks the intervention group showed no increased physical activity compared with the comparison group (weekly steps: change of +2420 vs ?12189 steps p=0.06; weekly moderate‐to‐vigorous physical activity: change of +70 vs +8min, p=0.06; weekly distance walked: change of +3 vs ?9.1km, p=0.05) and exercise knowledge (12% vs 1% improvement, p=0.08). There were no statistically significant differences for these outcomes at 20 weeks, or in self‐reported physical activity at 10 or 20 weeks. Interpretation There was a positive short‐term pattern for improvement in physical activity and knowledge. Internet‐based programs may offer an alternative for participants unable to attend regular face‐to‐face physical activity programs.     

Tongue muscle plasticity following hypoglossal nerve stimulation in aged rats

Introduction: Age‐related decreases in tongue muscle mass and strength have been reported. It may be possible to prevent age‐related tongue muscle changes using neuromuscular electrical stimulation (NMES). Our hypothesis was that alterations in muscle contractile properties and myosin heavy chain composition would be found after NMES. Methods: Fifty‐four young, middle‐aged, and old 344/Brown Norway rats were included in this study. Twenty‐four rats underwent bilateral electrical stimulation of the hypoglossal nerves for 8 weeks and were compared with control or sham rats. Muscle contractile properties and myosin heavy chain (MHC) in the genioglossus (GG), styloglossus (SG), and hyoglossus (HG) muscles were examined. Results: Compared with unstimulated control rats, we found reduced muscle fatigue, increased contraction and half‐decay times, and increased twitch and tetanic tension. Increased type I MHC was found, except for in GG in old and middle‐aged rats. Conclusion: Transitions in tongue muscle contractile properties and phenotype were found after NMES. Muscle Nerve, 2013     

The Effect of Fatigue on the Timing of Electrical Stimulation‐Evoked Muscle Contractions in People with Spinal Cord Injury

This study investigated the activation dynamics of electrical stimulation‐evoked muscle contractions performed by individuals with spinal cord injury (SCI). The purpose was to determine whether electrical stimulation (ES) firing patterns during cycling exercise should be altered in response to fatigue‐induced changes in the time taken for force to rise and fall with ES. Seven individuals with SCI performed isometric contractions and pedaled a motorized cycle ergometer with stimulation applied to the quadriceps muscles. Both exercise conditions were performed for five minutes while the patterns of torque production were recorded. ES‐evoked knee extension torque fell by 75% under isometric conditions, and the rate of force rise and decline decreased in proportion to torque (r = 0.91, r = 0.94, respectively). There was no change in the time for torque to rise to 50% of maximum levels. The time for torque to decline did increase slightly, but only during the first minute of exercise. Cycling power output fell approximately 50% during the five minutes of exercise, however, there was no change in the time taken for torque to rise or fall. The magnitude of ES‐evoked muscle torques decline substantially with fatigue, however, the overall pattern of torque production remained relatively unchanged. These results suggest there is no need to alter stimulation firing patterns to accommodate fatigue during ES‐evoked exercise.     

Test–retest reliability of wide‐pulse high‐frequency neuromuscular electrical stimulation evoked force

Introduction: We compare forces evoked by wide‐pulse high‐frequency (WPHF) neuromuscular electrical stimulation (NMES) delivered to a nerve trunk versus muscle belly and assess their test–retest intraindividual and interindividual reliability. Methods: Forces evoked during 2 sessions with WPHF NMES delivered over the tibial nerve trunk and 2 sessions over the triceps surae muscle belly were compared. Ten individuals participated in 4 sessions involving ten 20‐s WPHF NMES contractions interspaced by 40‐s recovery. Mean evoked force and force time integral of each contraction were quantified. Results: For both nerve trunk and muscle belly stimulation, intraindividual test–retest reliability was good (intraclass correlation coefficient > 0.9), and interindividual variability was large (coefficient of variation between 140% and 180%). Nerve trunk and muscle belly stimulation resulted in similar evoked forces. Discussion: WPHF NMES locations might be chosen by individual preference because intraindividual reliability was relatively good for both locations. Muscle Nerve 57 : E70–E77, 2018.     

Evoked EMG and Muscle Fatigue During Isokinetic FES-Cycling in Individuals With SCI

Purpose: This study investigated whether muscle fatigue during functional electrical stimulation (FES)‐induced cycling was associated with changes occurring in evoked electromyographic signals (eEMG, M‐waves) in individuals with spinal cord injury. We also explored the effects of recovery intervals between exercise sessions on the relationship between eEMG and muscle torque. Methods: Eight individuals with spinal cord injury performed three FES‐cycling sessions of 15‐min duration, with 5 min of recovery between them. The quadriceps muscles were electrically stimulated as the prime agonist to produce cycling. Pedal torques and surface eEMG signals were synchronously processed and recorded for offline analysis. Results: Large Torque decreases (20–44%) were observed in the first 5 min of cycling during the three exercise bouts, while changes of similar magnitude did not occur on any of the M‐wave time‐series (less than 19%). Between 5 and 15 min of cycling, muscle fatigue lowered the plateau baselines of Torque (ranging from 41% to 62%), M‐wave peak‐to‐peak amplitude (PtpA) and Area (ranging from 60% to 98%) time‐series, yet the magnitudes of these reductions were not consistent between them. Conclusion: We concluded that muscle fatigue during FES‐cycling was not associated with, nor could be predicted by, eEMG signals. Nonetheless, the consistency between M‐waves and Torque time‐curves in their direction of change clearly warrants further investigation.