Effect of citrulline malate supplementation on muscle function and bioenergetics during short-term repeated bouts of fatiguing exercise.

Citrulline malate (CM) has been shown to improve muscle performance in healthy participants during a single exercise session. Yet, within the framework of exercises repeated at close time interval, the consequences of CM ingestion on mechanical performance are controversial and the bioenergetics side remains undocumented. The aim of this double-blind placebo-controlled study was to evaluate in vivo the effect of short-term (7 doses in 48 h) oral administration of CM upon gastrocnemius muscle function and bioenergetics using non-invasive multimodal NMR techniques in healthy rats. The experimental protocol consisted of two 6-min bouts of fatiguing exercise spaced by an 8-min recovery period. CM treatment did not affect the basal bioenergetics status and increased the half-fatigue time during the first exercise bout. With exercise repetition, it prevented PCr cost alteration and decreased both the glycolytic ATP production and the contractile ATP cost in working muscle, but these changes were not associated to any improvement in mechanical performance. In addition, CM did not influence the replenishment of high-energy phosphorylated compounds during the post-exercise recovery periods. Therefore, short-term CM administration enhances muscle bioenergetics throughout fatiguing bouts of exercise repeated at close time interval but this enhancement does not benefit to mechanical performance.

Muscle alterations induced by electrostimulation are lower at short quadriceps femoris length.

PURPOSE: This study aimed at determining through MRI investigations, force and soreness assessments whether the modulation of muscle length is a relevant strategy for minimising neuromuscular electrical stimulation (NMES)-induced muscle damage in young healthy participants. METHODS: Comparison of 2 NMES sessions (40 isometric electrically-evoked contractions of the knee extensors) was randomly performed on 1 knee flexed at 50° (short muscle length) and the contralateral at 100° (long muscle length) in a single group of healthy participants. Indirect markers of muscle damage including changes in maximal voluntary isometric contraction (MVC) force, muscle volume and transverse relaxation time (T2) were measured before, 2 days (D2), 4 days (D4) and 7 days (D7) after the NMES sessions in each limb of the ten participants. RESULTS: Although stimulation intensity was similar during the NMES session on both limbs, significantly lower force production was recorded at long muscle length (peak at 30 ± 5% MVC force) as compared to short muscle length (peak at 61 ± 12% MVC force). In the following days, MVC force at long muscle length was decreased from D2 to D7, whereas no significant change occurred at short muscle length. Increases in muscle volume and T2 were found at each time point in stimulated muscles at long muscle length, whereas no change was found at short muscle length. CONCLUSION: For the same stimulation intensity, NMES-induced isometric contractions generate higher knee extension force output and result in lower muscle tissues alterations that could be related to a lower intramuscular shear strain when exercise is performed at short muscle length.

Spatial difference can occur between activated and damaged muscle areas following electrically-induced isometric contractions.

KEY POINTS: T2 mapping combined to image registration and statistical parametric mapping analysis is a suitable methodology to accurately localize and compare the extent of both activated and damaged muscle areas. Activated muscle areas following electrically-induced isometric contractions are superficial, but damaged regions are muscle specific and can be related to the muscle morphology and/or the relative spatial position within a muscle group leading to potential intramuscular muscle shear strain. Tissues other than active skeletal muscle fibres can be altered during unaccustomed neuromuscular electrical stimulation-induced isometric contractions. ABSTRACT: Skeletal muscle isometric contractions induced by neuromuscular electrical stimulation (NMES) exercise can generate damage within activated muscles. This study aimed at comparing the localization and the extent of NMES-activated muscle areas and induced damage regions using magnetic resonance imaging. Thirteen healthy subjects performed a single bout of NMES-induced isometric contractions known to induce a decrease in maximal voluntary isometric contraction (MVC) and increase in muscle volume and transverse relaxation time (T2 ). All the parameters were measured before, immediately after (POST), 7 days (D7), 14 days (D14) and 21 days (D21) after the NMES session. Spatial normalization of T2 maps were performed to compare the localization of muscle activation areas and damaged muscle regions from statistical mapping analyses. A significant decrease in MVC was found at POST (-26 ± 9%) and in delayed time at D7 (-20 ± 6%) and D14 (-12 ± 5%). Although muscle activation was statistically detected through T2 increase at POST in superficial parts of the two muscles located beneath the stimulation electrodes (i.e. vastus lateralis and vastus medialis), alterations quantified in a delayed time from increased T2 were mainly located in the deep muscle region of the vastus lateralis (+57 ± 24% of mean T2 ) and superficial area of the vastus medialis (+24 ± 16% of mean T2 ) at D7 and were still observed in whole muscle at D21. The discrepancy between activated and damaged areas in the vastus lateralis implies that tissues other than active skeletal muscle fibres were altered during unaccustomed NMES-induced isomeric contractions.

L-tyrosine supplementation does not ameliorate skeletal muscle dysfunction in zebrafish and mouse models of dominant skeletal muscle α-actin nemaline myopathy.

L-tyrosine supplementation may provide benefit to nemaline myopathy (NM) patients, however previous studies are inconclusive, with no elevation of L-tyrosine levels in blood or tissue reported. We evaluated the ability of L-tyrosine treatments to improve skeletal muscle function in all three published animal models of NM caused by dominant skeletal muscle α-actin (ACTA1) mutations. Highest safe L-tyrosine concentrations were determined for dosing water and feed of wildtype zebrafish and mice respectively. NM TgACTA1D286G-eGFP zebrafish treated with 10 µM L-tyrosine from 24 hours to 6 days post fertilization displayed no improvement in swimming distance. NM TgACTA1D286G mice consuming 2% L-tyrosine supplemented feed from preconception had significant elevations in free L-tyrosine levels in sera (57%) and quadriceps muscle (45%) when examined at 6-7 weeks old. However indicators of skeletal muscle integrity (voluntary exercise, bodyweight, rotarod performance) were not improved. Additionally no benefit on the mechanical properties, energy metabolism, or atrophy of skeletal muscles of 6-7 month old TgACTA1D286G and KIActa1H40Y mice eventuated from consuming a 2% L-tyrosine supplemented diet for 4 weeks. Therefore this study yields important information on aspects of the clinical utility of L-tyrosine for ACTA1 NM.

Is Branched-Chain Amino Acids Supplementation an Efficient Nutritional Strategy to Alleviate Skeletal Muscle Damage? A Systematic Review.

Amino acids and more precisely, branched-chain amino acids (BCAAs), are usually consumed as nutritional supplements by many athletes and people involved in regular and moderate physical activities regardless of their practice level. BCAAs have been initially shown to increase muscle mass and have also been implicated in the limitation of structural and metabolic alterations associated with exercise damage. This systematic review provides a comprehensive analysis of the literature regarding the beneficial effects of BCAAs supplementation within the context of exercise-induced muscle damage or muscle injury. The potential benefit of a BCAAs supplementation was also analyzed according to the supplementation strategy-amount of BCAAs, frequency and duration of the supplementation-and the extent of muscle damage. The review protocol was registered prospectively with Prospective Register for Systematic Reviews (registration number CRD42017073006) and followed Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Literature search was performed from the date of commencement until August 2017 using four online databases (Medline, Cochrane library, Web of science and ScienceDirect). Original research articles: (i) written in English; (ii) describing experiments performed in Humans who received at least one oral BCAAs supplementation composed of leucine, isoleucine and valine mixture only as a nutritional strategy and (iii) reporting a follow-up of at least one day after exercise-induced muscle damage, were included in the systematic review analysis. Quality assessment was undertaken independently using the Quality Criteria Checklist for Primary Research. Changes in indirect markers of muscle damage were considered as primary outcome measures. Secondary outcome measures were the extent of change in indirect markers of muscle damage. In total, 11 studies were included in the analysis. A high heterogeneity was found regarding the different outcomes of these studies. The risk of bias was moderate considering the quality ratings were positive for six and neutral for three. Although a small number of studies were included, BCAAs supplementation can be efficacious on outcomes of exercise-induced muscle damage, as long as the extent of muscle damage was low-to-moderate, the supplementation strategy combined a high daily BCAAs intake (>200 mg kg-1 day-1) for a long period of time (>10 days); it was especially effective if taken prior to the damaging exercise.

Specific brain activation patterns associated with two neuromuscular electrical stimulation protocols.

The influence of neuromuscular electrical stimulation (NMES) parameters on brain activation has been scarcely investigated. We aimed at comparing two frequently used NMES protocols - designed to vary in the extent of sensory input. Whole-brain functional magnetic resonance imaging was performed in sixteen healthy subjects during wide-pulse high-frequency (WPHF, 100 Hz-1 ms) and conventional (CONV, 25 Hz-0.05 ms) NMES applied over the triceps surae. Each protocol included 20 isometric contractions performed at 10% of maximal force. Voluntary plantar flexions (VOL) were performed as control trial. Mean force was not different among the three protocols, however, total current charge was higher for WPHF than for CONV. All protocols elicited significant activations of the sensorimotor network, cerebellum and thalamus. WPHF resulted in lower deactivation in the secondary somatosensory cortex and precuneus. Bilateral thalami and caudate nuclei were hyperactivated for CONV. The modulation of the NMES parameters resulted in differently activated/deactivated regions related to total current charge of the stimulation but not to mean force. By targeting different cerebral brain regions, the two NMES protocols might allow for individually-designed rehabilitation training in patients who can no longer execute voluntary movements.

Effects of branched-chain amino acids supplementation on both plasma amino acids concentration and muscle energetics changes resulting from muscle damage: A randomized placebo controlled trial.

BACKGROUND & AIMS: Branched-chain amino acids promote muscle-protein synthesis, reduce protein oxidation and have positive effects on mitochondrial biogenesis and reactive oxygen species scavenging. The purpose of the study was to determine the potential benefits of branched-chain amino acids supplementation on changes in force capacities, plasma amino acids concentration and muscle metabolic alterations after exercise-induced muscle damage. METHODS: (31)P magnetic resonance spectroscopy and biochemical analyses were used to follow the changes after such damage. Twenty six young healthy men were randomly assigned to supplemented branched-chain amino acids or placebo group. Knee extensors maximal voluntary isometric force was assessed before and on four days following exercise-induced muscle damage. Concentrations in phosphocreatine [PCr], inorganic phosphate [Pi] and pH were measured during a standardized rest-exercise-recovery protocol before, two (D2) and four (D4) days after exercise-induced muscle damage. RESULTS: No significant difference between groups was found for changes in maximal voluntary isometric force (-24% at D2 and -21% at D4). Plasma alanine concentration significantly increased immediately after exercise-induced muscle damage (+25%) in both groups while concentrations in glycine, histidine, phenylalanine and tyrosine decreased. No difference between groups was found in the increased resting [Pi] (+42% at D2 and +34% at D4), decreased resting pH (-0.04 at D2 and -0.03 at D4) and the slower PCr recovery rate (-18% at D2 and -24% at D4). CONCLUSIONS: The damaged muscle was not able to get benefits out of the increased plasma branched-chain amino acids availability to attenuate changes in indirect markers of muscle damage and muscle metabolic alterations following exercise-induced muscle damage.

Capsiate supplementation reduces oxidative cost of contraction in exercising mouse skeletal muscle in vivo.

Chronic administration of capsiate is known to accelerate whole-body basal energy metabolism, but the consequences in exercising skeletal muscle remain very poorly documented. In order to clarify this issue, the effect of 2-week daily administration of either vehicle (control) or purified capsiate (at 10- or 100-mg/kg body weight) on skeletal muscle function and energetics were investigated throughout a multidisciplinary approach combining in vivo and in vitro measurements in mice. Mechanical performance and energy metabolism were assessed strictly non-invasively in contracting gastrocnemius muscle using magnetic resonance (MR) imaging and 31-phosphorus MR spectroscopy (31P-MRS). Regardless of the dose, capsiate treatments markedly disturbed basal bioenergetics in vivo including intracellular pH alkalosis and decreased phosphocreatine content. Besides, capsiate administration did affect neither mitochondrial uncoupling protein-3 gene expression nor both basal and maximal oxygen consumption in isolated saponin-permeabilized fibers, but decreased by about twofold the Km of mitochondrial respiration for ADP. During a standardized in vivo fatiguing protocol (6-min of repeated maximal isometric contractions electrically induced at a frequency of 1.7 Hz), both capsiate treatments reduced oxidative cost of contraction by 30-40%, whereas force-generating capacity and fatigability were not changed. Moreover, the rate of phosphocreatine resynthesis during the post-electrostimulation recovery period remained unaffected by capsiate. Both capsiate treatments further promoted muscle mass gain, and the higher dose also reduced body weight gain and abdominal fat content. These findings demonstrate that, in addition to its anti-obesity effect, capsiate supplementation improves oxidative metabolism in exercising muscle, which strengthen this compound as a natural compound for improving health.

Heterogeneity of muscle damage induced by electrostimulation: a multimodal MRI study.

PURPOSE: Neuromuscular electrostimulation (NMES) leads to a spatially fixed, synchronous, and superficial motor unit recruitment, which could induce muscle damage. Therefore, the extent of muscle damage and its spatial occurrence were expected to be heterogeneous across and along the quadriceps femoris (QF) muscles. The aim of the present study was to characterize muscle spatial heterogeneity in QF damage after a single bout of isometric NMES using multimodal magnetic resonance imaging (MRI). METHODS: Twenty-five young healthy males participated in this study. MRI investigations consisted of the assessment of muscle volume, transverse relaxation time (T2), and diffusion tensor imaging (DTI) in muscles positioned near the stimulation electrodes (i.e., vastus lateralis (VL) and vastus medialis (VM)) and muscles located outside the stimulated regions (i.e., vastus intermedius and rectus femoris). These measurements were performed 6 d before, and 2 d and 4 d (D4) after the NMES session. RESULTS: For the muscles placed in direct contact with the stimulation electrodes, volume (VL, +8.5%; VM, +3.8%), T2 (VL, +19.5%; VM, +6.7%) and radial diffusivity (λ3) (VL, + 7.3%; VM, +3.7%) significantly increased at D4. Whereas MRI parameter changes were larger for VL as compared with those for other QF muscles at D4, homogeneous alterations were found along all QF muscles. CONCLUSIONS: Isometric NMES induced specific and localized alterations in VL and VM, with heterogeneous damage amplitude among them. Potential effects of unaccustomed intermuscle shear stress during electrically evoked isometric contractions could be a key factor in the spatial occurrence and the extent of damage among QF muscles (especially in VL). The kinetics and extent of MRI changes varied between T2 and diffusion tensor imaging metrics, suggesting the involvement of different physiological processes.

Impaired mitochondrial function and reduced energy cost as a result of muscle damage.

PURPOSE: Although it has been largely acknowledged that isometric neuromuscular electrostimulation (NMES) exercise induces larger muscle damage than voluntary contractions, the corresponding effects on muscle energetics remain to be determined. Voluntary exercise-induced muscle damage (EIMD) has been reported to have minor slight effects on muscle metabolic response to subsequent dynamic exercise, but the magnitude of muscle energetics alterations for NMES EIMD has never been documented. METHODS: ³¹P magnetic resonance spectroscopy measurements were performed in 13 young healthy males during a standardized rest-exercise-recovery protocol before (D0) and 2 d (D2) and 4 d (D4) after NMES EIMD on knee extensor muscles. Changes in kinetics of phosphorylated metabolite concentrations (i.e., phosphocreatine [PCr], inorganic phosphate [Pi], and adenosine triphosphate [ATP]) and pH were assessed to investigate aerobic and anaerobic rates of ATP production and energy cost of contraction (Ec). RESULTS: Resting [Pi]/[PCr] ratio increased at D2 (+39%) and D4 (+29%), mainly owing to the increased [Pi] (+43% and +32%, respectively), whereas a significant decrease in resting pH was determined (-0.04 pH unit and -0.03 pH unit, respectively). PCr recovery rate decreased at D2 (-21%) and D4 (-23%) in conjunction with a significantly decreased total rate of ATP production at D4 (-18%) mainly owing to an altered aerobic ATP production (-19%). Paradoxically, Ec was decreased at D4 (-21%). CONCLUSION: Overall, NMES EIMD led to intramuscular acidosis in resting muscle and mitochondrial impairment in exercising muscle. Alterations of noncontractile processes and/or adaptive mechanisms to muscle damage might account for the decreased Ec during the dynamic exercise.

Time course of central and peripheral alterations after isometric neuromuscular electrical stimulation-induced muscle damage.

Isometric contractions induced by neuromuscular electrostimulation (NMES) have been shown to result in a prolonged force decrease but the time course of the potential central and peripheral factors have never been investigated. This study examined the specific time course of central and peripheral factors after isometric NMES-induced muscle damage. Twenty-five young healthy men were subjected to an NMES exercise consisting of 40 contractions for both legs. Changes in maximal voluntary contraction force of the knee extensors (MVC), peak evoked force during double stimulations at 10 Hz (Db(10)) and 100 Hz (Db(100)), its ratio (10:100), voluntary activation, muscle soreness and plasma creatine kinase activity were assessed before, immediately after and throughout four days after NMES session. Changes in knee extensors volume and T2 relaxation time were also assessed at two (D2) and four (D4) days post-exercise. MVC decreased by 29% immediately after NMES session and was still 19% lower than the baseline value at D4. The decrease in Db(10) was higher than in Db(100) immediately and one day post-exercise resulting in a decrease (-12%) in the 10:100 ratio. On the contrary, voluntary activation significantly decreased at D2 (-5%) and was still depressed at D4 (-5%). Muscle soreness and plasma creatine kinase activity increased after NMES and peaked at D2 and D4, respectively. T2 was also increased at D2 (6%) and D4 (9%). Additionally, changes in MVC and peripheral factors (e.g., Db(100)) were correlated on the full recovery period, while a significant correlation was found between changes in MVC and VA only from D2 to D4. The decrease in MVC recorded immediately after the NMES session was mainly due to peripheral changes while both central and peripheral contributions were involved in the prolonged force reduction. Interestingly, the chronological events differ from what has been reported so far for voluntary exercise-induced muscle damage.

Vitamin D protects against diet-induced obesity by enhancing fatty acid oxidation.

Prospective studies reported an inverse correlation between 25-hydroxyvitamin D [25(OH)D] plasma levels and prevalence of obesity and type 2 diabetes. In addition, 25(OH)D status may be a determinant of obesity onset. However, the causality between these observations is not yet established. We studied the preventive effect of vitamin D3 (VD3) supplementation (15,000 IU/kg of food for 10 weeks) on onset of obesity in a diet-induced obesity mouse model. We showed that the VD3 supplementation limited weight gain induced by high-fat diet, which paralleled with an improvement of glucose homeostasis. The limitation of weight gain could further be explained by an increased lipid oxidation, possibly due to an up-regulation of genes involved in fatty acid oxidation and mitochondrial metabolism, leading to increased energy expenditure. Altogether, these data show that VD3 regulates energy expenditure and suggest that VD3 supplementation may represent a strategy of preventive nutrition to fight the onset of obesity and associated metabolic disorders.

A single intake of capsiate improves mechanical performance and bioenergetics efficiency in contracting mouse skeletal muscle.

Capsiate is known to increase whole body oxygen consumption possibly via the activation of uncoupling processes, but its effect at the skeletal muscle level remains poorly documented and conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated in mice 2 h after a single intake of either vehicle (control) or purified capsiate (at 10 or 100 mg/kg body wt) through a multidisciplinary approach combining in vivo and in vitro measurements. Mechanical performance and energy pathway fluxes were assessed strictly noninvasively during a standardized electrostimulation-induced exercise, using an original device implementing 31-phosphorus magnetic resonance spectroscopy, and mitochondrial respiration was evaluated in isolated saponin-permeabilized fibers. Compared with control, both capsiate doses produced quantitatively similar effects at the energy metabolism level, including an about twofold decrease of the mitochondrial respiration sensitivity for ADP. Interestingly, they did not alter either oxidative phosphorylation or uncoupling protein 3 gene expression at rest. During 6 min of maximal repeated isometric contractions, both doses reduced the amount of ATP produced from glycolysis and oxidative phosphorylation but increased the relative contribution of oxidative phosphorylation to total energy turnover (+28 and +21% in the 10- and 100-mg groups, respectively). ATP cost of twitch force generation was further reduced in the 10- (-35%) and 100-mg (-45%) groups. Besides, the highest capsiate dose also increased the twitch force-generating capacity. These data present capsiate as a helpful candidate to enhance both muscle performance and oxidative phosphorylation during exercise, which could constitute a nutritional approach for improving health and preventing obesity and associated metabolic disorders.

Lack of myostatin impairs mechanical performance and ATP cost of contraction in exercising mouse gastrocnemius muscle in vivo.

Although it is well established that the lack of myostatin (Mstn) promotes skeletal muscle hypertrophy, the corresponding changes regarding force generation have been studied mainly in vitro and remain conflicting. Furthermore, the metabolic underpinnings of these changes are very poorly documented. To clarify this issue, we have investigated strictly noninvasively in vivo the impact of the lack of Mstn on gastrocnemius muscle function and energetics in Mstn-targeted knockout (Mstn-/-) mice using ¹H-magnetic resonance (MR) imaging and ³¹P-MR spectroscopy during maximal repeated isometric contractions induced by transcutaneous electrostimulation. In Mstn-/- animals, although body weight, gastrocnemius muscle volume, and absolute force were larger (+38, +118, and +34%, respectively) compared with wild-type (Mstn+/+) mice, specific force (calculated from MR imaging measurements) was significantly lower (-36%), and resistance to fatigue was decreased. Besides, Mstn deficiency did not affect phosphorylated compound concentrations and intracellular pH at rest but caused a large increase in ATP cost of contraction (up to +206% compared with Mstn+/+) throughout the stimulation period. Further, Mstn deficiency limits the shift toward oxidative metabolism during muscle activity despite the fact that oxidative ATP synthesis capacity was not altered. Our data demonstrate in vivo that the absence of Mstn impairs both mechanical performance and energy cost of contraction in hypertrophic muscle. These findings must be kept in mind when considering Mstn as a potential therapeutic target for increasing muscle mass in patients suffering from muscle-wasting disorders.

A strictly noninvasive MR setup dedicated to longitudinal studies of mechanical performance, bioenergetics, anatomy, and muscle recruitment in contracting mouse skeletal muscle.

MR techniques have proven their ability to investigate skeletal muscle function in situ. Their benefit in terms of noninvasiveness is, however, lost in animal research, given that muscle stimulation and force output measurements are usually achieved using invasive surgical procedures, thereby excluding repeated investigations in the same animal. This study describes a new setup allowing strictly noninvasive investigations of mouse gastrocnemius muscle function using (1)H-MRI and (31)P-MR spectroscopy. Its originality is to integrate noninvasive systems for inducing muscle contraction through transcutaneous stimulation and for measuring mechanical performance with a dedicated ergometer. In order to test the setup, muscle function was investigated using a fatiguing stimulation protocol (6 min of repeated isometric contractions at 1.7 Hz). T(2)-weighted imaging demonstrated that transcutaneous stimulation mainly activated the gastrocnemius. Moreover, investigations repeated twice with a 7-day interval between bouts did show a high reproducibility in measurements with regard to changes in isometric force and energy metabolism. In conclusion, this setup enables us for the first time to access mechanical performance, energy metabolism, anatomy, and physiology strictly noninvasively in contracting mouse skeletal muscle. The possibility for implementing longitudinal studies opens up new perspectives in many research areas, including ageing, pharmaceutical research, and gene and cell therapy.

Effects of stimulation frequency and pulse duration on fatigue and metabolic cost during a single bout of neuromuscular electrical stimulation.

We have investigated the effects of stimulation frequency and pulse duration on fatigue and energy metabolism in rat gastrocnemius muscle during a single bout of neuromuscular electrical stimulation (NMES). Electrical pulses were delivered at 100 Hz (1-ms pulse duration) and 20 Hz (5-ms pulse duration) for the high (HF) and low (LF) frequency protocols, respectively. As a standardization procedure, the averaged stimulation intensity, the averaged total charge, the initial peak torque, the duty cycle, the contraction duration and the torque-time integral were similar in both protocols. Fatigue was assessed using two testing trains delivered at a frequency of 100 Hz and 20 Hz before and after each protocol. Metabolic changes were investigated in vivo using 31P-magnetic resonance spectroscopy (31P-MRS) and in vitro in freeze-clamped muscles. Both LF and HF NMES protocols induced the same decrease in testing trains and metabolic changes. We conclude that, under carefully controlled and comparable conditions, the use of low stimulation frequency and long pulse duration do not minimize the occurrence of muscle fatigue or affect the corresponding stimulation-induced metabolic changes so that this combination of stimulation parameters would not be adequate in the context of rehabilitation.

Electrostimulation improves muscle perfusion but does not affect either muscle deoxygenation or pulmonary oxygen consumption kinetics during a heavy constant-load exercise.

Electromyostimulation (EMS) is commonly used as part of training programs. However, the exact effects at the muscle level are largely unknown and it has been recently hypothesized that the beneficial effect of EMS could be mediated by an improved muscle perfusion. In the present study, we investigated rates of changes in pulmonary oxygen consumption (VO(2p)) and muscle deoxygenation during a standardized exercise performed after an EMS warm-up session. We aimed at determining whether EMS could modify pulmonary O(2) uptake and muscle deoxygenation as a result of improved oxygen delivery. Nine subjects performed a 6-min heavy constant load cycling exercise bout preceded either by an EMS session (EMS) or under control conditions (CONT). VO(2p) and heart rate (HR) were measured while deoxy-(HHb), oxy-(HbO(2)) and total haemoglobin/myoglobin (Hb(tot)) relative contents were measured using near infrared spectroscopy. EMS significantly increased (P < 0.05) the Hb(tot) resting level illustrating a residual hyperaemia. The EMS priming exercise did not affect either the HHb time constant (17.7 +/- 14.2 s vs. 13.1 +/- 2.3 s under control conditions) or the VO(2p) kinetics (time-constant = 18.2 +/- 5.2 s vs. 15.4 +/- 4.6 s under control conditions). Likewise, the other VO(2p) parameters were unchanged. Our results further indicated that EMS warm-up improved muscle perfusion through a residual hyperaemia. However, neither VO(2p) nor [HHb] kinetics were modified accordingly. These results suggest that improved O(2) delivery by residual hyperaemia induced by EMS does not accelerate the rate of aerobic metabolism during heavy exercise at least in trained subjects.

Investigation of muscle bioenergetics in the Marfan syndrome indicates reduced metabolic efficiency.

BACKGROUND: The Marfan syndrome is an inherited multisystem disorder caused by mutations in fibrillin 1, with cardiovascular involvement being the most important feature of the phenoptype. Affected individuals have impaired flow-mediated dilatation (FMD) of large arteries of a similar severity to patients with chronic heart failure (CHF). AIMS: Skeletal muscle bioenergetics were studied in patients with the Marfan syndrome in order to evaluate the impact of impaired flow-mediated dilatation on skeletal muscle metabolism. Skeletal muscle metabolism is abnormal in CHF and the aetiology is unclear. METHODS: Thirteen patients and 12 controls were studied by phosphorus Magnetic Resonance spectroscopy of the calf muscle using an incremental exercise protocol and by Magnetic Resonance imaging. RESULTS: Metabolic variables measured at rest were normal in Marfan patients. For a similar total work output measured at end of the standardized incremental exercise, the total rate of energy consumption (EC) was significantly increased in patients (21.2 +/- 2.3 mM ATP/min/W vs 13.6 +/- 1.4 mM ATP/min/W in controls). Similarly, both PCr and pH time-dependent changes were significantly different between groups. The absolute contributions of aerobic and glycolytic pathways to energy production were significantly higher in patients whereas they were similar when expressed relative to EC. CONCLUSIONS: The higher EC measured in patients with Marfan syndrome was supported by both oxidative and anaerobic metabolic pathways, thereby suggesting a decrease in muscle efficiency and/or muscle mass, as previously described in other diseases affecting skeletal muscle function such as heart failure and peripheral vascular disease.

Multiminicore disease in a family susceptible to malignant hyperthermia: histology, in vitro contracture tests, and genetic characterization.

BACKGROUND: Histological anomalies associated with malignant hyperthermia (MH) have been scarcely reported. In some patients susceptible to MH (MHS), central cores have been identified and a genetic association has been proposed, but multiminicore lesions have not been systematically reported. OBJECTIVE: To analyze the association between multiminicores and MHS in a large family with MH with an approach combining histology, in vitro contracture tests, and genetic analysis. PATIENTS AND METHODS: Twenty-nine members of an MH family (147 members) were investigated. MAIN OUTCOME MEASURES: Muscle biopsy specimens were analyzed histologically and with in vitro contracture tests. Genetic analyses were performed to determine the presence of mutations in the ryanodine receptor (RYR1) gene. RESULTS: According to the gold standard in vitro contracture tests, 17 patients were diagnosed as having MHS and 10 as not being susceptible. Multiminicores were found in 16 of the 17 MHS patients and in a single nonsusceptible participant. A linkage between the MH trait and the RYR1 locus in chromosome 19 was demonstrated, whereas no already known mutations were found. Two missense heterozygous mutations (R2676W and T2787S) were identified from sequencing of the entire coding complementary DNA. Overall, we found a significant association between MHS and the presence of multiminicores (chi(2) = 26.5, P<.001) on the one hand and the presence of new mutations in the RYR1 gene (chi(2) = 19.0, P<.001) on the other hand. This remarkably high occurrence of multiminicores in an MHS family is uncommon, and genetic analyses indicate that the association between multiminicores and MHS is linked to a novel R2656W and T2787S substitution present on the same allele of the RYR1 gene. CONCLUSIONS: These results indicate that multiminicore lesions are observed in MHS patients with neither clinical signs related to multiminicore disease nor histological features of congenital myopathies. These multiminicore lesions may be secondary to mutations in the RYR1 gene. As a consequence, these patients must be distinguished from patients with multiminicore disease and from other MHS patients for whom multiminicores are not observed.