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1.
Sensors (Basel) ; 21(21)2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34770555

RESUMO

BACKGROUND: Clinical applications of conventional functional electrical stimulation (FES) administered via a single electrode are limited by rapid onset neuromuscular fatigue. "Sequential" (SEQ) stimulation, involving the rotation of pulses between multiple active electrodes, has been shown to reduce fatigue compared to conventional FES. However, there has been limited adoption of SEQ in research and clinical settings. METHODS: The SEQ adapter is a small, battery-powered device that transforms the output of any commercially available electrical stimulator into SEQ stimulation. We examined the output of the adaptor across a range of clinically relevant stimulation pulse parameters to verify the signal integrity preservation ability of the SEQ adapter. Pulse frequency, amplitude, and duration were varied across discrete states between 4 and 200 Hz, 10 and100 mA, and 50 and 2000 µs, respectively. RESULTS: A total of 420 trials were conducted, with 80 stimulation pulses per trial. The SEQ adapter demonstrated excellent preservation of signal integrity, matching the pulse characteristics of the originating stimulator within 1% error. The SEQ adapter operates as expected at pulse frequencies up to 160 Hz, failing at a frequency of 200 Hz. CONCLUSION: The SEQ adapter represents an effective and low-cost solution to increase the utilization of SEQ in existing rehabilitation paradigms.


Assuntos
Terapia por Estimulação Elétrica , Fadiga Muscular , Estimulação Elétrica , Eletrodos , Músculo Esquelético
2.
Artigo em Inglês | MEDLINE | ID: mdl-33465028

RESUMO

Transcutaneous neuromuscular electrical stimulation (NMES) can be used to activate the quadriceps femoris muscle to produce knee extension torque via seven distinct motor points, defined as the most sensitive locations on the muscle belly to electrical stimuli. However, it remains unclear how much individual motor points of the quadriceps femoris muscle contribute to the knee joint torque. Here we systematically investigated the contribution of each motor point of the quadriceps femoris muscle to the knee joint torque produced by paired electrical stimuli. Ten able-bodied individuals participated in this study. Paired electrical stimuli was applied by delivering electrical impulses on the motor points in all combinations among seven motor points (i.e., totaling to 127 combinations) at two different stimulation intensities (i.e., 25% and 50% of the maximum) while recording isometric knee joint torque. The contribution of individual motor points was estimated using statistical analyses. We found that a linear addition of twitch torques induced by single motor point stimulus overestimated the twitch torques induced by multiple motor point stimulations, suggesting overlaps in muscle fibres activated by each motor point. Using multiple linear regressions, we identified the average contribution of each motor point to the knee extension torque during paired electrical stimuli and found significant differences between these torque contributions. We demonstrated that seven distinct motor points can be activated for the quadriceps muscle group using paired electrical stimuli and identified the contribution of each motor point to knee extension torque during twitch muscle contraction; these findings provide useful information to design rehabilitation using NMES on quadriceps femoris muscles.


Assuntos
Contração Muscular , Músculo Quadríceps , Estimulação Elétrica , Humanos , Contração Isométrica , Articulação do Joelho , Torque
3.
Neurosci Lett ; 736: 135246, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32673689

RESUMO

Electrical stimulation for inducing muscle contraction can be divided into peripheral nerve stimulation (PNS) and motor point stimulation (MPS). Although the neural pathways activated by PNS have been well studied, those by MPS are still unclear. Here we investigated whether MPS activates Ia-sensory nerves and induces antidromic firing of motor nerves. Ten able-bodied males and females participated in this study. We confirmed that soleus MPS did not induce the H-reflex while soleus PNS did. Furthermore, MPS of the tibialis anterior muscle did not induce the reciprocal inhibition of soleus muscle while PNS did. For testing the effect of MPS on motor neuron excitability, we examined the H-reflex modulation by soleus MPS. When the conditioning and test interval was under 100-ms and the conditioning stimulus intensity was above 30-mA, soleus MPS induced the H-reflex inhibition. This suggests that soleus MPS produces antidromic firing that can induce after-hyperpolarization. These results suggest that MPS predominantly activates the motor nerve without depolarizing the Ia-sensory nerve. Since MPS is applicable to larger number of muscles compared to PNS, utilizing MPS can lead to more versatile neuromodulation of the spinal cord.


Assuntos
Estimulação Elétrica/métodos , Neurônios Motores/fisiologia , Músculo Esquelético/inervação , Células Receptoras Sensoriais/fisiologia , Adulto , Feminino , Reflexo H/fisiologia , Humanos , Masculino , Contração Muscular/fisiologia , Adulto Jovem
4.
IEEE Trans Neural Syst Rehabil Eng ; 27(8): 1566-1573, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31265401

RESUMO

Neuromuscular electrical stimulation is conventionally applied through a single pair of electrodes over the muscle belly, denominated single electrode stimulation (SES). SES is limited by discomfort and incomplete motor-unit recruitment, restricting electrically-evoked torque and promoting premature fatigue-induced torque-decline. Sequential stimulation involving rotation of pulses between multiple pairs of electrodes has been proposed as an alternative, denominated spatially distributed sequential stimulation (SDSS). The present aim was to compare discomfort, maximal-tolerated torque, and fatigue-related outcomes between SES and SDSS of tibialis anterior. Ten healthy participants completed two experimental sessions. The self-reported discomfort at sub-maximal torque, the maximal-tolerated torque, fatigue-induced torque-decline during, and doublet-twitch torque at 10- and 100-Hz before and after, 300 intermittent (0.6-s-ON-0.6-s-OFF) isokinetic contractions were compared between SES and SDSS. SDSS stimulation improved fatigue-related outcomes, whereas increased discomfort and reduced maximal-tolerated torque. SDSS holds promise for reducing fatigue. However, limited torque production and associated discomfort may limit its utility for rehabilitation/training.


Assuntos
Fadiga Muscular/fisiologia , Músculo Esquelético/fisiologia , Adulto , Estimulação Elétrica , Eletrodos , Feminino , Humanos , Contração Isométrica/fisiologia , Masculino , Neurônios Motores/fisiologia , Contração Muscular/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Músculo Esquelético/inervação , Reabilitação/métodos , Torque , Adulto Jovem
5.
J Spinal Cord Med ; 40(6): 715-722, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28899231

RESUMO

CONTEXT: Firing rates of single cortical neurons can be volitionally modulated through biofeedback (i.e. operant conditioning), and this information can be transformed to control external devices (i.e. brain-machine interfaces; BMIs). However, not all neurons respond to operant conditioning in BMI implementation. Establishing criteria that predict neuron utility will assist translation of BMI research to clinical applications. FINDINGS: Single cortical neurons (n=7) were recorded extracellularly from primary motor cortex of a Long-Evans rat. Recordings were incorporated into a BMI involving up-regulation of firing rate to control the brightness of a light-emitting-diode and subsequent reward. Neurons were classified as 'fast-spiking', 'bursting' or 'regular-spiking' according to waveform-width and intrinsic firing patterns. Fast-spiking and bursting neurons were found to up-regulate firing rate by a factor of 2.43±1.16, demonstrating high utility, while regular-spiking neurons decreased firing rates on average by a factor of 0.73±0.23, demonstrating low utility. CONCLUSION/CLINICAL RELEVANCE: The ability to select neurons with high utility will be important to minimize training times and maximize information yield in future clinical BMI applications. The highly contrasting utility observed between fast-spiking and bursting neurons versus regular-spiking neurons allows for the hypothesis to be advanced that intrinsic electrophysiological properties may be useful criteria that predict neuron utility in BMI implementation.


Assuntos
Interfaces Cérebro-Computador , Córtex Motor/fisiologia , Neurônios/fisiologia , Potenciais de Ação , Animais , Córtex Motor/citologia , Reabilitação Neurológica/métodos , Projetos Piloto , Ratos , Ratos Long-Evans
6.
Phys Ther ; 97(8): 790-789, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28789468

RESUMO

BACKGROUND: The benefits of neuromuscular electrical stimulation (NMES) for rehabilitation depend on the capacity to generate functionally relevant torque with minimal fatigability and discomfort. Traditionally, NMES is delivered either over a muscle belly (mNMES) or a nerve trunk (nNMES). Recently, a technique that minimizes contraction fatigability by alternating pulses between the mNMES and nNMES sites, termed "interleaved" NMES (iNMES), was developed. However, discomfort and the ability to generate large torque during iNMES have not been explored adequately. OBJECTIVE: The study objective was to compare discomfort and maximal torque between mNMES, nNMES, and iNMES. METHODS: Stimulation trains (12 pulses at 40 Hz) were delivered to produce dorsiflexion torque using mNMES, nNMES, and iNMES. Discomfort was assessed using a visual analogue scale for contractions that generated 5-30% of a maximal voluntary isometric contraction (MVIC), and for the maximal tolerable torque. RESULTS: Discomfort scores were not different between NMES types when torque was ≤20% MVIC. At 30% MVIC, mNMES produced more discomfort than nNMES and iNMES. nNMES produced the most torque (65% MVIC), followed by iNMES (49% MVIC) and mNMES (33% MVIC); in these trials, mNMES produced more discomfort than nNMES, but not iNMES. LIMITATIONS: The present results may be limited to individuals with no history of neuromusculoskeletal impairment. CONCLUSIONS: In terms of discomfort, there were no differences between mNMES, nNMES, or iNMES for contractions between 5-20% MVIC. However, mNMES produced more discomfort than nNMES and iNMES for contractions of 30% MVIC, while for larger contractions, mNMES only produced more discomfort than nNMES. The advantages and disadvantages of each NMES type should be considered prior to implementation in rehabilitation programs.


Assuntos
Articulação do Tornozelo/fisiologia , Terapia por Estimulação Elétrica/métodos , Contração Isométrica/fisiologia , Músculo Esquelético/fisiologia , Dor/etiologia , Amplitude de Movimento Articular/fisiologia , Adulto , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Humanos , Masculino , Torque , Adulto Jovem
7.
J Spinal Cord Med ; 40(6): 733-747, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28703038

RESUMO

CONTEXT: Endocrine-metabolic disease (EMD) risk following spinal cord injury (SCI) is associated with significant multi-morbidity (i.e. fracture, diabetes, heart disease), mortality, and economic burden. It is unclear to what extent rehabilitation interventions can modify EMD risk and improve health status in community-dwelling adults with chronic SCI. OBJECTIVES: To characterize rehabilitation interventions and summarize evidence on their efficacy/effectiveness to modify precursors to EMD risk in community-dwelling adults with chronic SCI. METHODS: Systematic searches of MEDLINE PubMed, EMBASE Ovid, CINAHL, CDSR, and PsychInfo were completed. All randomized, quasi-experimental, and prospective controlled trials comparing rehabilitation/therapeutic interventions with control/placebo interventions in adults with chronic SCI were eligible. Two authors independently selected studies and abstracted data. Mean differences of change from baseline were reported for EMD risk outcomes. The GRADE approach was used to rate the quality of evidence. RESULTS: Of 489 articles identified, 16 articles (11 studies; n=396) were eligible for inclusion. No studies assessed the effects of rehabilitation interventions on incident fragility fractures, heart disease, and/or diabetes. Individual studies reported that exercise and/or nutrition interventions could improve anthropometric indices, body composition/adiposity, and biomarkers. However, there were also reports of non-statistically significant between-group differences. CONCLUSIONS: There was very low-quality evidence that rehabilitation interventions can improve precursors to EMD risk in community-dwelling adults with chronic SCI. The small number of studies, imprecise estimates, and inconsistency across studies limited our ability to make conclusions. A high-quality longitudinal intervention trial is needed to inform community-based rehabilitation strategies for EMD risk after chronic SCI.


Assuntos
Doenças do Sistema Endócrino/prevenção & controle , Terapia por Exercício/métodos , Doenças Metabólicas/prevenção & controle , Reabilitação Neurológica/métodos , Terapia Nutricional/métodos , Traumatismos da Medula Espinal/reabilitação , Doenças do Sistema Endócrino/etiologia , Terapia por Exercício/efeitos adversos , Humanos , Vida Independente , Doenças Metabólicas/etiologia , Terapia Nutricional/efeitos adversos , Traumatismos da Medula Espinal/complicações
8.
Muscle Nerve ; 56(5): 989-993, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28245521

RESUMO

INTRODUCTION: Neuromuscular electrical stimulation (NMES) over a muscle belly (mNMES) recruits superficial motor units (MUs) preferentially, whereas NMES over a nerve trunk (nNMES) recruits MUs evenly throughout the muscle. We performed tests to determine whether "interleaving" pulses between the mNMES and nNMES sites (iNMES) reduces the fatigability of contractions for people experiencing paralysis because of chronic spinal cord injury. METHODS: Plantar flexion torque and soleus electromyography (M-waves) were recorded from 8 participants. A fatigue protocol (75 contractions; 2 s on/2 s off for 5 min) was delivered by iNMES. The results were compared with previously published data collected with mNMES and nNMES in the same 8 participants. RESULTS: Torque declined ∼40% more during mNMES than during nNMES or iNMES. M-waves declined during mNMES but not during nNMES or iNMES. DISCUSSION: To reduce fatigability of electrically evoked contractions of paralyzed plantar flexors, iNMES is equivalent to nNMES, and both are superior to mNMES. Muscle Nerve 56: 989-993, 2017.


Assuntos
Estimulação Elétrica/métodos , Junção Neuromuscular/fisiologia , Traumatismos da Medula Espinal/terapia , Adulto , Biofísica , Eletromiografia , Fadiga/etiologia , Fadiga/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/fisiologia , Recrutamento Neurofisiológico/fisiologia , Traumatismos da Medula Espinal/complicações , Torque , Resultado do Tratamento
9.
Muscle Nerve ; 55(2): 179-189, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27313001

RESUMO

INTRODUCTION: Neuromuscular electrical stimulation (NMES) can be delivered over a muscle belly (mNMES) or nerve trunk (nNMES). Both methods generate contractions that fatigue rapidly due, in part, to non-physiologically high motor unit (MU) discharge frequencies. In this study we introduce interleaved NMES (iNMES), whereby stimulus pulses are alternated between mNMES and nNMES. iNMES was developed to recruit different MU populations with every other stimulus pulse, with a goal of reducing discharge frequencies and muscle fatigue. METHODS: Torque and electromyography were recorded during fatigue protocols (12 min, 240 contractions) delivered using mNMES, nNMES, and iNMES. RESULTS: Torque declined significantly 3 min into iNMES and 1 min into both mNMES and nNMES. Torque decreased by 39% during iNMES and by 67% and 58% during mNMES and nNMES, respectively. CONCLUSIONS: iNMES resulted in less muscle fatigue than mNMES and nNMES. Delivering NMES in ways that reduce MU discharge frequencies holds promise for reducing muscle fatigue during NMES-based rehabilitation. Muscle Nerve, 2016 Muscle Nerve 55: 179-189, 2017.


Assuntos
Estimulação Elétrica/métodos , Contração Muscular/fisiologia , Fadiga Muscular/fisiologia , Junção Neuromuscular/fisiologia , Adolescente , Adulto , Análise de Variância , Biofísica , Eletromiografia , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético , Torque , Adulto Jovem
10.
Muscle Nerve ; 55(4): 490-499, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27422814

RESUMO

INTRODUCTION: In this study, we quantified the "overlap" between motor units recruited by single pulses of neuromuscular electrical stimulation (NMES) delivered over the tibialis anterior muscle (mNMES) and the common peroneal nerve (nNMES). We then quantified the torque produced when pulses were alternated between the mNMES and nNMES sites at 40 Hz ("interleaved" NMES; iNMES). METHODS: Overlap was assessed by comparing torque produced by twitches evoked by mNMES, nNMES, and both delivered together, over a range of stimulus intensities. Trains of iNMES were delivered at the intensity that produced the lowest overlap. RESULTS: Overlap was lowest (5%) when twitches evoked by both mNMES and nNMES produced 10% peak twitch torque. iNMES delivered at this intensity generated 25% of maximal voluntary dorsiflexion torque (11 Nm). DISCUSSION: Low intensity iNMES leads to low overlap and produces torque that is functionally relevant to evoke dorsiflexion during walking. Muscle Nerve 55: 490-499, 2017.


Assuntos
Contração Muscular/fisiologia , Junção Neuromuscular/fisiologia , Recrutamento Neurofisiológico/fisiologia , Adulto , Estimulação Elétrica , Eletromiografia , Feminino , Humanos , Modelos Lineares , Masculino , Músculo Esquelético/fisiologia , Torque , Caminhada/fisiologia , Adulto Jovem
11.
Muscle Nerve ; 56(2): 271-281, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27862023

RESUMO

INTRODUCTION: Transcutaneous neuromuscular electrical stimulation (NMES) can generate muscle contractions for rehabilitation and exercise. However, NMES-evoked contractions are limited by fatigue when they are delivered "conventionally" (CONV) using a single active electrode. Researchers have developed "sequential" (SEQ) stimulation, involving rotation of pulses between multiple "aggregated" (AGGR-SEQ) or "distributed" (DISTR-SEQ) active electrodes, to reduce fatigue (torque-decline) by reducing motor unit discharge rates. The primary objective was to compare fatigue-related outcomes, "potentiation," "variability," and "efficiency" between CONV, AGGR-SEQ, and DISTR-SEQ stimulation of knee extensors in healthy participants. METHODS: Torque and current were recorded during testing with fatiguing trains using each NMES type under isometric and isokinetic (180°/s) conditions. RESULTS: Compared with CONV stimulation, SEQ techniques reduced fatigue-related outcomes, increased potentiation, did not affect variability, and reduced efficiency. CONCLUSIONS: SEQ techniques hold promise for reducing fatigue during NMES-based rehabilitation and exercise; however, optimization is required to improve efficiency. Muscle Nerve 56: 271-281, 2017.


Assuntos
Fadiga/fisiopatologia , Fadiga/reabilitação , Contração Muscular/fisiologia , Estimulação Elétrica Nervosa Transcutânea , Adulto , Biofísica , Eletrodos , Eletromiografia , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Pessoa de Meia-Idade , Torque , Adulto Jovem
12.
Muscle Nerve ; 50(2): 224-34, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24638882

RESUMO

INTRODUCTION: Neuromuscular electrical stimulation (NMES) over a muscle belly (mNMES) generates contractions predominantly through M-waves, while NMES over a nerve trunk (nNMES) can generate contractions through H-reflexes in people who are neurologically intact. We tested whether the differences between mNMES and nNMES are present in people with chronic motor-complete spinal cord injury and, if so, whether they influence contraction fatigue. METHODS: Plantar-flexion torque and soleus electromyography were recorded from 8 participants. Fatigue protocols were delivered using mNMES and nNMES on separate days. RESULTS: nNMES generated contractions that fatigued less than mNMES. Torque decreased the least when nNMES generated contractions, at least partly through H-reflexes (n = 4 participants; 39% decrease), and torque decreased the most when contractions were generated through M-waves, regardless of NMES site (nNMES 71% decrease, n = 4; mNMES, 73% decrease, n = 8). CONCLUSIONS: nNMES generates contractions that fatigue less than mNMES, but only when H-reflexes contribute to the evoked contractions.


Assuntos
Fadiga/etiologia , Reflexo H/fisiologia , Contração Muscular/fisiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/patologia , Adulto , Análise de Variância , Estimulação Elétrica , Eletromiografia , Potencial Evocado Motor/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Recrutamento Neurofisiológico/fisiologia , Torque
13.
Clin Neurophysiol ; 124(11): 2257-63, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23692977

RESUMO

OBJECTIVE: To compare the spatial distribution of motor units recruited in tibialis anterior (TA) when electrical stimulation is applied over the TA muscle belly versus the common peroneal nerve trunk. METHODS: Electromyography (EMG) was recorded from the surface and from fine wires in superficial and deep regions of TA. Separate M-wave recruitment curves were constructed for muscle belly and nerve trunk stimulation. RESULTS: During muscle belly stimulation, significantly more current was required to generate M-waves that were 5% of the maximal M-wave (M max; M5%max), 50% M max (M 50%max) and 95% M max (M 95%max) at the deep versus the superficial recording site. In contrast, during nerve trunk stimulation, there were no differences in the current required to reach M5%max, M 50%max or M 95%max between deep and superficial recording sites. Surface EMG reflected activity in both superficial and deep muscle regions. CONCLUSIONS: Stimulation over the muscle belly recruited motor units from superficial to deep with increasing stimulation amplitude. Stimulation over the nerve trunk recruited superficial and deep motor units equally, regardless of stimulation amplitude. SIGNIFICANCE: These results support the idea that where electrical stimulation is applied markedly affects how contractions are produced and have implications for the interpretation of surface EMG data.


Assuntos
Estimulação Elétrica/métodos , Músculo Esquelético/inervação , Recrutamento Neurofisiológico/fisiologia , Adulto , Eletromiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nervo Fibular/fisiologia , Adulto Jovem
14.
J Neurophysiol ; 103(3): 1295-303, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20053846

RESUMO

Recruitment and repetitive firing of spinal motoneurons depend on the activation of persistent inward calcium and sodium currents (PICs) that are in turn facilitated by serotonin and norepinephrine that arise primarily from the brain stem. Considering that in rats motoneuron PICs are greatly facilitated by increasing the presynaptic release of norepinephrine with amphetamine, we sought similar evidence for the modulation of PICs in human motoneurons. Pairs of motor units were recorded during a gradually increasing and then decreasing voluntary contraction. The firing frequency (F) of the lower-threshold (control) motor unit was used as an estimate of the synaptic input to the higher-threshold (test) motor unit. Generally, PICs are initiated during the recruitment of a motoneuron and subsequently provide a fixed depolarizing current that helps the synaptic input maintain firing until derecruitment. Thus the amplitude of the PIC in the test motor unit was estimated from the difference in synaptic input (DeltaF) needed to maintain minimal firing once the PIC was fully activated (measured at the time of test unit derecruitment) compared with the larger synaptic input required to initiate firing prior to full PIC activation (measured at the time of test unit recruitment; DeltaF = F(recruit) - F(derecruit)). Moreover, the activation time of the PIC was estimated as the minimal contraction duration needed to produce a maximal PIC (DeltaF). In five subjects, oral administration of amphetamine, but not placebo, increased the DeltaF by 62% [from 3.7 +/- 0.6 to 6.0 +/- 0.8 (SD) imp/s, P = 0.001] and decreased the time needed to activate a maximal DeltaF from approximately 2 to 0.5 s. Both findings suggest that the endogenous facilitation of PICs from brain stem derived norepinephrine plays an important role in modulating human motoneuron excitability, readying motoneurons for rapid and sustained activity during periods of high arousal such as stress or fear.


Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Anfetamina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Neurônios Motores/efeitos dos fármacos , Músculo Esquelético/inervação , Canais de Sódio/efeitos dos fármacos , Adulto , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Cafeína/farmacologia , Eletrofisiologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Músculo Esquelético/efeitos dos fármacos , Norepinefrina/metabolismo , Canais de Sódio/fisiologia
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