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 remains 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.
This study compared the metabolic and activation changes induced by electrically-evoked (NMES) and voluntary (VOL) contractions performed at the same submaximal intensity using P chemical shift imaging (CSI) and T2 mapping investigations.
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 was expected to be heterogeneous across and along 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 by using multimodal magnetic resonance imaging (MRI).
We compared the extent and origin of muscle fatigue induced by short-pulse-low-frequency [conventional (CONV)] and wide-pulse-high-frequency (WPHF) neuromuscular electrical stimulation. We expected CONV contractions to mainly originate from depolarization of axonal terminal branches (spatially determined muscle fiber recruitment) and WPHF contractions to be partly produced via a central pathway (motor unit recruitment according to size principle). Greater neuromuscular fatigue was, therefore, expected following CONV compared with WPHF. Fourteen healthy subjects underwent 20 WPHF (1 ms-100 Hz) and CONV (50 ?s-25 Hz) evoked isometric triceps surae contractions (work/rest periods 20:40 s) at an initial target of 10% of maximal voluntary contraction (MVC) force. Force-time integral of the 20 evoked contractions (FTI) was used as main index of muscle fatigue; MVC force loss was also quantified. Central and peripheral fatigue were assessed by voluntary activation level and paired stimulation amplitudes, respectively. FTI in WPHF was significantly lower than in CONV (21,717 ± 11,541 vs. 37,958 ± 9,898 N·s P<0,001). The reductions in MVC force (WPHF: -7.0 ± 2.7%; CONV: -6.2 ± 2.5%; P < 0.01) and paired stimulation amplitude (WPHF: -8.0 ± 4.0%; CONV: -7.4 ± 6.1%; P < 0.001) were similar between conditions, whereas no change was observed for voluntary activation level (P > 0.05). Overall, our results showed a different motor unit recruitment pattern between the two neuromuscular electrical stimulation modalities with a lower FTI indicating greater muscle fatigue for WPHF, possibly limiting the presumed benefits for rehabilitation programs.
We have designed and constructed an experimental set-up allowing electrical stimulation of hindlimb mouse muscles and the corresponding force measurements at high-field (11.75T). We performed high-resolution multimodal MRI (including T2 -weighted imaging, angiography and diffusion) and analysed the corresponding MRI changes in response to a stimulation protocol. Mice were tested twice over a 1-week period to investigate the reliability of mechanical measurements and T2 changes associated with the stimulation protocol. Additionally, angiographic images were obtained before and immediately after the stimulation protocol. Finally, multislice diffusion imaging was performed before, during and immediately after the stimulation session. Apparent diffusion coefficient (ADC) maps were calculated on the basis of diffusion weighted images (DWI). Both force production and T2 values were highly reproducible as illustrated by the low coefficient of variation (<8%) and high intraclass correlation coefficient (?0.75) values. Maximum intensity projection angiographic images clearly showed a strong vascular effect resulting from the stimulation protocol. Although a motion sensitive imaging sequence was used (echo planar imaging) and in spite of the strong muscle contractions, motion artifacts were minimal for DWI recorded under exercising conditions, thereby underlining the robustness of the measurements. Mean ADC values increased under exercising conditions and were higher during the recovery period as compared with the corresponding control values. The proposed experimental approach demonstrates accurate high-field multimodal MRI muscle investigations at a preclinical level which is of interest for monitoring the severity and/or the progression of neuromuscular diseases but also for assessing the efficacy of potential therapeutic interventions.
Nemaline myopathy is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. The first disease causing mutation (Met9Arg) was identified in the gene encoding ?-tropomyosin slow gene (TPM3). Considering the conflicting findings of the previous studies on the transgenic (Tg) mice carrying the TPM3Met9Arg mutation, we investigated carefully the effect of the Met9Arg mutation in 8-9 month-old Tg(TPM3)Met9Arg mice on muscle function using a multiscale methodological approach including skinned muscle fibers analysis and in vivo investigations by magnetic resonance imaging and 31-phosphorus magnetic resonance spectroscopy. While in vitro maximal force production was reduced in Tg(TPM3)Met9Arg mice as compared to controls, in vivo measurements revealed an improved mechanical performance in the transgenic mice as compared to the former. The reduced in vitro muscle force might be related to alterations occurring at the cross-bridges level with muscle-specific underlying mechanisms. In vivo muscle improvement was not associated with any changes in either muscle volume or energy metabolism. Our findings indicate that TPM3(Met9Arg) mutation leads to a mild muscle weakness in vitro related to an alteration at the cross-bridges level and a paradoxical gain of muscle function in vivo. These results clearly point out that in vitro alterations are muscle-dependent and do not necessarily translate into similar changes in vivo.
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.
Nemaline myopathy (NM), the most common non-dystrophic congenital disease of skeletal muscle, can be caused by mutations in the skeletal muscle ?-actin gene (ACTA1) (~25% of all NM cases and up to 50% of severe forms of NM). Muscle function of the recently generated transgenic mouse model carrying the human Asp286Gly mutation in the ACTA1 gene (Tg(ACTA1)(Asp286Gly)) has been mainly investigated in vitro. Therefore, we aimed at providing a comprehensive picture of the in vivo hindlimb muscle function of Tg(ACTA1)(Asp286Gly) mice by combining strictly noninvasive investigations. Skeletal muscle anatomy (hindlimb muscles, intramuscular fat volumes) and microstructure were studied using multimodal magnetic resonance imaging (Dixon, T2, Diffusion Tensor Imaging [DTI]). Energy metabolism was studied using 31-phosphorus Magnetic Resonance Spectroscopy ((31)P-MRS). Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (1-150 Hz) and a fatigue protocol (6 min-1.7 Hz). Tg(ACTA1)(Asp286Gly) mice showed a mild muscle weakness as illustrated by the reduction of both absolute (30%) and specific (15%) maximal force production. Dixon MRI did not show discernable fatty infiltration in Tg(ACTA1)(Asp286Gly) mice indicating that this mouse model does not reproduce human MRI findings. Increased T2 values were observed in Tg(ACTA1)(Asp286Gly) mice and might reflect the occurrence of muscle degeneration/regeneration process. Interestingly, T2 values were linearly related to muscle weakness. DTI experiments indicated lower ?2 and ?3 values in Tg(ACTA1)(Asp286Gly) mice, which might be associated to muscle atrophy and/or the presence of histological anomalies. Finally (31)P-MRS investigations illustrated an increased anaerobic energy cost of contraction in Tg(ACTA1)(Asp286Gly) mice, which might be ascribed to contractile and non-contractile processes. Overall, we provide a unique set of information about the anatomic, metabolic and functional consequences of the Asp286Gly mutation that might be considered as relevant biomarkers for monitoring the severity and/or the progression of NM and for assessing the efficacy of potential therapeutic interventions.
Nemaline myopathy (NM) is the most common disease entity among non-dystrophic skeletal muscle congenital diseases. Mutations in the skeletal muscle ?-actin gene (ACTA1) account for ?25% of all NM cases and are the most frequent cause of severe forms of NM. So far, the mechanisms underlying muscle weakness in NM patients remain unclear. Additionally, recent Magnetic Resonance Imaging (MRI) studies reported a progressive fatty infiltration of skeletal muscle with a specific muscle involvement in patients with ACTA1 mutations. We investigated strictly noninvasively the gastrocnemius muscle function of a mouse model carrying a mutation in the ACTA1 gene (H40Y). Skeletal muscle anatomy (hindlimb muscles and fat volumes) and energy metabolism were studied using MRI and (31)Phosphorus magnetic resonance spectroscopy. Skeletal muscle contractile performance was investigated while applying a force-frequency protocol (from 1-150 Hz) and a fatigue protocol (80 stimuli at 40 Hz). H40Y mice showed a reduction of both absolute (-40%) and specific (-25%) maximal force production as compared to controls. Interestingly, muscle weakness was associated with an improved resistance to fatigue (+40%) and an increased energy cost. On the contrary, the force frequency relationship was not modified in H40Y mice and the extent of fatty infiltration was minor and not different from the WT group. We concluded that the H40Y mouse model does not reproduce human MRI findings but shows a severe muscle weakness which might be related to an alteration of intrinsic muscular properties. The increased energy cost in H40Y mice might be related to either an impaired mitochondrial function or an alteration at the cross-bridges level. Overall, we provided a unique set of anatomic, metabolic and functional biomarkers that might be relevant for monitoring the progression of NM disease but also for assessing the efficacy of potential therapeutic interventions at a preclinical level.
While muscle damage resulting from electrically-induced muscle isometric contractions has been reported in humans, animal studies have failed to illustrate similar deleterious effects and it remains to be determined whether these conflicting results are related to differences regarding experimental procedures or to species. We have investigated in vivo, in rat gastrocnemius muscles, using experimental conditions as close as possible to those used in humans (i.e., muscle length, number of contractions, stimulated muscle), the effects of a single bout of neuromuscular electrical stimulation (NMES). Maximal tetanic force was measured before, immediately after and 1h and 1, 2, 3, 7 and 14 days after NMES. Magnetic resonance imaging measurements, including volume of gastrocnemius muscles and proton transverse relaxation time (T(2)) were performed at baseline and 3, 7, and 14 days after the NMES session. Control animals did not perform any exercise and measurements were recorded at the same time points. For both groups, blood creatine kinase (CK) activity was measured within the first 3 days that followed the initial evaluation. Maximal tetanic force decreased immediately after NMES whereas measurements performed 1h and the days afterwards were similar to the baseline values. CK activity, muscle volume and T(2) values were similar throughout the experimental protocol between the two groups. Under carefully controlled experimental conditions, isometric NMES per se did not induce muscle damage in rat gastrocnemius muscles on the contrary to what has been repeatedly reported in humans. Further experiments would then be warranted in order to clearly delineate these differences and to better understand the physiological events associated with muscle damage resulting from NMES-induced isometric contractions.
We aimed at providing an overview of the currently acknowledged benefits and limitations of neuromuscular electrical stimulation (NMES) training programs in both healthy individuals and in recreational and competitive athletes regarding muscle performance. Typical NMES resistance exercises are performed under isometric conditions and involve the application of electrical stimuli delivered as intermittent high frequencies trains (>40-50 Hz) through surface electrodes. NMES has been acknowledged as an efficient modality leading to significant improvements in isometric maximal voluntary strength. However, the resulting changes in dynamic strength, motor performance skills and explosive movements (i.e., jump performance, sprint ability) are still ambiguous and could only be obtained when NMES is combined with voluntary dynamic exercise such as plyometrics. Additionally, the effects of NMES on muscle fatigability are still poorly understood and required further investigations. While NMES effectiveness could be partially related to several external adjustable factors such as training intensity, current characteristics (e.g., intensity, pulse duration…) or the design of training protocols (number of contractions per session, number of sessions per week…), anatomical specificities (e.g., morphological organization of the axonal branches within the muscle) appear as the main factor accounting for the differences in NMES response. Overall, NMES cannot be considered as a surrogate training method, but rather as an adjunct to voluntary resistance training. The combination of these two training modalities should optimally improve muscle function.
The aim of the present study was to define the chronic effects of neuromuscular electrical stimulation (NMES) on the neuromuscular properties of human skeletal muscle. Eight young healthy male subjects were subjected to 25 sessions of isometric NMES of the quadriceps muscle over an 8-wk period. Needle biopsies were taken from the vastus lateralis muscle before and after training. The training status, myosin heavy chain (MHC) isoform distribution, and global protein pattern, as assessed by proteomic analysis, widely varied among subjects at baseline and prompted the identification of two subgroups: an "active" (ACT) group, which performed regular exercise and had a slower MHC profile, and a sedentary (SED) group, which did not perform any exercise and had a faster MHC profile. Maximum voluntary force and neural activation significantly increased after NMES in both groups (+?30% and +?10%, respectively). Both type 1 and 2 fibers showed significant muscle hypertrophy. After NMES, both groups showed a significant shift from MHC-2X toward MHC-2A and MHC-1, i.e., a fast-to-slow transition. Proteomic maps showing ?500 spots were obtained before and after training in both groups. Differentially expressed proteins were identified and grouped into functional categories. The most relevant changes regarded 1) myofibrillar proteins, whose changes were consistent with a fast-to-slow phenotype shift and with a strengthening of the cytoskeleton; 2) energy production systems, whose changes indicated a glycolytic-to-oxidative shift in the metabolic profile; and 3) antioxidant defense systems, whose changes indicated an enhancement of intracellular defenses against reactive oxygen species. The adaptations in the protein pattern of the ACT and SED groups were different but were, in both groups, typical of both resistance (i.e., strength gains and hypertrophy) and endurance (i.e., a fast-to-slow shift in MHC and metabolic profile) training. These training-induced adaptations can be ascribed to the peculiar motor unit recruitment pattern associated with NMES.
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.
The purpose of this study was to test the hypothesis that group III and IV muscle afferent activity would differ after concentric- and eccentric-type fatiguing tasks. Tibialis anterior afferent activities from adult rats were measured in three conditions: before and after a rest period (C), and after concentric (CC) or eccentric (EC) exercise. Specific activators were used to elicit increases in afferent discharge rates, i.e., electrically induced fatigue (EIF), or potassium chloride (KCl) and lactic acid (LA) injections. After the rest period (POST-condition), the control group displayed a pattern of response to stimuli similar to that obtained in baseline condition (PRE-condition). However, responses were significantly different in the exercise groups: afferent responses were blunted in the CC group and were almost suppressed in the EC group. These results demonstrate that the type of muscular contraction involved in the fatiguing task can affect group III and IV afferent fiber activity differently and, potentially, can differentially affect the regulation of central motor command.
A recent study has demonstrated that neuromuscular electrical stimulation (NMES) determines, in vitro, a fast-to-slow shift in the metabolic profile of muscle fibers. The aim of the present study was to evaluate if, in the same subjects, these changes would translate, in vivo, into an enhanced skeletal muscle oxidative metabolism. Seven young men were tested (cycle ergometer) during incremental exercises up to voluntary exhaustion and moderate and heavy constant-load exercises (CLE). Measurements were carried out before and after an 8-wk training program by isometric bilateral NMES (quadriceps muscles), which induced an ?25% increase in maximal isometric force. Breath-by-breath pulmonary O(2) uptake (Vo(2)) and vastus lateralis oxygenation indexes (by near-infrared spectroscopy) were determined. Skeletal muscle fractional O(2) extraction was estimated by near-infrared spectroscopy on the basis of changes in concentration of deoxygenated hemoglobin + myoglobin. Values obtained at exhaustion were considered "peak" values. The following functional evaluation variables were unaffected by NMES: peak Vo(2); gas exchange threshold; the Vo(2) vs. work rate relationship (O(2) cost of cycling); changes in concentration of deoxygenated hemoglobin + myoglobin vs. work rate relationship (related to the matching between O(2) delivery and Vo(2)); peak fractional O(2) extraction; Vo(2) kinetics (during moderate and heavy CLE) and the amplitude of its slow component (during heavy CLE). Thus NMES did not affect several variables of functional evaluation of skeletal muscle oxidative metabolism. Muscle hypertrophy induced by NMES could impair peripheral O(2) diffusion, possibly counterbalancing, in vivo, the fast-to-slow phenotypic changes that were observed in vitro, in a previous work, in the same subjects of the present study.
The aim of this study was to evaluate the effect of the playing surface properties on the development of neuromuscular fatigue in tennis.
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