Skeletal Muscle Fatigability Research Articles

Effect of tirasemtiv, a selective activator of the fast skeletal muscle troponin complex, in patients with peripheral artery disease.

Tirasemtiv (CK-2017357), a novel small-molecule activator of the fast skeletal muscle troponin complex, slows the rate of calcium release from troponin, thus sensitizing fast skeletal muscle fibers to calcium. In preclinical studies, tirasemtiv increased muscle force and delayed the onset and reduced the extent of muscle fatigue during hypoxia in vitro and muscle ischemia in situ. This study evaluated the effect of single doses of tirasemtiv on measures of skeletal muscle function and fatigability in patients with stable calf claudication due to peripheral artery disease (PAD). Sixty-one patients with an ankle-brachial index ≤0.90 in the leg with claudication received single double-blind doses of tirasemtiv 375 mg and 750 mg and matching placebo in random order about 1 week apart. After 33 patients were treated, the 750 mg dose was decreased to 500 mg due to adverse events and these dose groups were combined for analysis. On each study day, bilateral heel-raise testing was performed before and at 3 and 6 hours after dosing; a 6-minute walk test was performed at 4 hours after dosing. Claudicating calf muscle performance was increased at the highest dose and plasma concentration of tirasemtiv; however, the 6-minute walk distance decreased with both the dose and plasma concentration of tirasemtiv, possibly due to dose-related adverse events, particularly dizziness, that could impede walking ability. In conclusion, the mechanism of fast skeletal muscle troponin activation improved muscle function but not 6-minute walking distance in patients with claudication due to PAD. CLINICALTRIALSGOV IDENTIFIER NCT01131013:

Autoantibodies to low-density lipoprotein receptor-related protein 4 that is essential for the neuromuscular junction formation

Myasthenia gravis (MG) is an autoimmune disorder characterized by skeletal muscle fatigability and muscle weakness resulting from inhibition of neuromuscular transmission by autoantibodies against synaptic apparatus in the neuromuscular junction (NMJ). MG is probably classified into three groups: anti-acetylcholine receptor (AChR) antibody-positive MG; antimuscle-specific kinase (MuSK) antibody-positive MG; and seronegative MG, which is negative for both antibodies. In patients with seronegative MG, pathogenic factors remain elusive. Recently, a new autoantibody against low-density lipoprotein receptor-related protein 4 (Lrp4), which is one of the postsynaptic apparatus and indispensable for the formation of the NMJ, has been identified and has attracted attention as a third MG-related autoantibody. In the present review, we discuss the role of Lrp4 in the formation of NMJ, and the molecular mechanism(s) of pathogenesis for anti-Lrp4 antibody-positive MG.

Von Hippel-Lindau disease associated with myasthenia gravis not related to thymoma

BACKGROUND Von Hippel-Lindau disease (VHL) is a rare autosomal dominant inherited disorder characterized by an increased risk of tumours in a number of locations (eyes, brain, adrenal gland, pancreas, liver, kidneys, or other areas of the body). It is caused by germline mutation in the VHL gene. The VHL gene is a tumour suppressor gene that has been identified on the short arm of chromosome 3. CASE REPORT We report a case of a 60 year-old female with the clinical diagnosis of VHL type 1 (cerebellar haemangioblastoma, pancreatic cysts with subsequent steatorrhoea, and bilateral renal carcinoma) who developed weakness and fatigability of skeletal muscles, left lid ptosis, snarling expression and nasal timbre speech. Acetylcholine receptor antibodies were negative in serum, while the electrodiagnostic test demonstrated an alteration of neuromuscolar junction which was consistent with the diagnosis of myasthenia gravis. Contrast-enhanced TC scan of the anterior mediastinum was performed, which excluded thymus enlargement. VHL gene evaluation in this patient identified a new mutation (c279delC9) and polymorphism c291C>G. At present the patient still suffers from ataxia and dysmetria due to cerebellar involvement in VHL, while fatigue and lid ptosis improved after the treatment with oral pyridostigmine 60 mg tid. DISCUSSION AND CONCLUSIONS To our knowledge this is the first report of a case of VHL associated with myasthenia gravis without thymoma. A case of VHL associated with a form of myasthenia gravis related to thymoma has been recently reported. In our case the absence of acetylcholine receptor antibodies may suggest a genetic origin also for the myasthenia gravis.

Increased systemic TNFα reduces skeletal muscle capillarity but does not change skeletal muscle fatigability in a mouse model of COPD

Increased systemic inflammation is associated with several different pathologies, including chronic obstructive pulmonary disease(COPD). Systemic inflammation may be the link between central pathology and resultant skeletal muscle comorbidity. We hypothesized that a lung‐specific TNFa overexpressing mouse(shown to have increased circulating TNFa)would have decreased capillarity and increased in vivo muscle fatigue. We measured in vivo muscle fatigue by stimulating the tibial nerve and measuring muscle force using as standardized 3 minute fatigue protocol. After this protocol animals were sacrificed and hindlimb muscle removed for morphometric and molecular analysis. We found that TNFα overexpressing mice had no difference in overall muscle fatigue compared to littermate controls. Although circulating TNFa was elevated by 300%, no difference in skeletal muscle TNFα levels were seen. TNFa overexpressing mice exhibited lower skeletal muscle capillarity in the soleus muscle(down 16%) but not in the plantaris, compared to controls. Surprisingly, no differences in the angiogenic proteins VEGF or TSP‐1 were observed in any muscles. These data suggest that there is a muscle type specific response to capillary rarefaction caused by systemically elevated TNFα. Funding:T32NIH5T32HL090610

Myasthenics of guntur

Introduction: Myasthenia gravis (MG) is a neuromuscular disorder characterized by weakness and fatigability of skeletal muscles. There is a paucity of data regarding the disease in the state of Andhra Pradesh. Objective: Our aim was to study the clinical profile of patients with myasthenia gravis admitted to government general hospital, Guntur, Andhra Pradesh. Materials and Methods: We studied the cases of 36 myasthenia gravis patients admitted to the government general hospital, Guntur from September 2003 to April 2011. Results: The median age of presentation was 40 years. Male to female ratio was 3:1. The presenting complaint was ptosis in 44.44% of the cases. The other major complaint was lower limb weakness (38.89%). Serum levels of acetylcholine receptor (AChRs) antibodies were more in males (18) than in females (9.22). Conclusion: The median age of presentation and sex ratio matched that with the pattern in India. Ptosis may suggest a possibility of myasthenia gravis to the clinician more easily than any other complaint.

T.O.7 Blockade of Myostatin/ActRIIB signalling induces skeletal muscle fatigability and exercise intolerance

<h2>Abstract</h2> Blockade of myostatin/ActRIIB signaling has been proposed as a therapeutic strategy for Duchenne muscular dystrophy (DMD) because of its supposed stimulating effect on skeletal muscle size and function. Here we show that constitutive lack of myostatin in Mstn−/− mice resulted in increased muscle fatigability, decreased exercise performance, exercise-induced abnormal lactic acidemia and decreased mitochondrial respiration. However, Mstn−/− mice develop a fiber type disproportion towards a glycolytic muscle phenotype with less mitochondria and decreased capillary density, and these developmental abnormalities may account for the observed changes in muscle function and energy metabolism. To determine the role of myostatin/ActRIIB signaling on adult muscle physiology and metabolism, we treated adult wild type mice and mdx mice for 4months with soluble Activin IIB receptor (sActRIIB-Fc) in order to block signaling by myostatin and homologous proteins. In wild type mice, sAcRIIB-Fc strongly increased muscle size and tetanic force, whereas fatigue resistance decreased. Mice exhausted precociously during treadmill exercise and this was associated with grossly elevated serum lactate levels. Treatment of mdx mice with sActRIIB-Fc, however, resulted in largely decreased specific force. Mdx mice developed extreme exercise intolerance and exercise induced lactate acidosis. Mitochondrial enzyme activities and fiber type distribution remained unchanged, thus a primary mitochondrial deficit was unlikely the cause of the exercise failure. Importantly, capillary density of muscle strongly decreased following treatment with sActRIIB-Fc and this was associated with marked dystrophic changes. Our results suggest that myostatin optimizes muscle metabolism by adapting muscle vascularization to oxygen requirements. Blockade of myostatin/ActRIIB signaling causes a capillary-fiber mismatch especially in de- and regenerating dystrophic muscle, provoking a secondary metabolic myopathy.

Significance of Group III and IV muscle afferents for the endurance exercising human

1. With the onset of dynamic whole-body exercise, contraction-induced mechanical and biochemical stimuli within locomotor muscle cause an increase in the discharge frequency of thinly myelinated (Group III) and unmyelinated (Group IV) nerve fibres located within the muscle. 2. These thin fibre muscle afferents project to various sites within the central nervous system and thereby substantially influence the exercising human. 3. First, Group III/IV muscle afferents are the afferent arm of cardiovascular and ventilatory reflex responses that are mediated in the nucleus tractus solitarius and the ventrolateral medulla. Therefore, neural feedback from working skeletal muscle is a vital component in providing a high capacity for endurance exercise because muscle perfusion and O₂ delivery determine the fatigability of skeletal muscle. 4. Second, Group III/IV muscle afferents facilitate 'central fatigue' (failure, or unwillingness, of the central nervous system to 'drive' motoneurons) by exerting inhibitory influences on central motor drive during exercise. 5. Thus, Group III/IV muscle afferents play a substantial role in a human's susceptibility to fatigue and capacity for endurance exercise.

Loss of IL-15 receptor α alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles

IL-15 receptor α (IL-15Rα) is a component of the heterotrimeric plasma membrane receptor for the pleiotropic cytokine IL-15. However, IL-15Rα is not merely an IL-15 receptor subunit, as mice lacking either IL-15 or IL-15Rα have unique phenotypes. IL-15 and IL-15Rα have been implicated in muscle phenotypes, but a role in muscle physiology has not been defined. Here, we have shown that loss of IL-15Rα induces a functional oxidative shift in fast muscles, substantially increasing fatigue resistance and exercise capacity. IL-15Rα-knockout (IL-15Rα-KO) mice ran greater distances and had greater ambulatory activity than controls. Fast muscles displayed fatigue resistance and a slower contractile phenotype. The molecular signature of these muscles included altered markers of mitochondrial biogenesis and calcium homeostasis. Morphologically, fast muscles had a greater number of muscle fibers, smaller fiber areas, and a greater ratio of nuclei to fiber area. The alterations of physiological properties and increased resistance to fatigue in fast muscles are consistent with a shift toward a slower, more oxidative phenotype. Consistent with a conserved functional role in humans, a genetic association was found between a SNP in the IL15RA gene and endurance in athletes stratified by sport. Therefore, we propose that IL-15Rα has a role in defining the phenotype of fast skeletal muscles in vivo.

Systematic Review and Meta-Analysis of Skeletal Muscle Fatigue in Old Age

Despite intense interest in understanding how old age may alter skeletal muscle fatigability, a quantitative examination of the impact of study design on age-related differences in muscle fatigue does not exist. The purpose of this study was to conduct a systematic review of the differences in muscle fatigue between young and older adults, with specific examination of moderator variables suggested to contribute to discrepancies across studies: contraction intensity, contraction mode, duty cycle, fatigue index, sex, muscle group, and contraction type. The standardized effect of age on muscle fatigue was computed for 37 studies (60 standardized effects). Standardized effects were coded as positive when less fatigue was reported in older individuals compared with young individuals. The overall standardized effect of age on muscle fatigue was positive (0.56). In studies using dynamic contractions or using muscle power as the index of fatigue, the standardized effect was negative (-0.12 and -2.5, respectively). The standardized effect for all other moderator categories was positive (range = 0.09-0.90), indicating less fatigue in older adults under all other methodological conditions. This review provides the first quantitative analysis of the effect of study design on age-related differences in muscle fatigue. The results indicate that older individuals develop less muscle fatigue than young individuals, particularly during isometric contractions of the elbow flexor and knee extensor muscles. However, the results also suggest that older adults develop greater fatigue during dynamic contractions, particularly when the decline in power is assessed. Studies that verify this latter outcome are needed, as are studies designed to elucidate the mechanisms of fatigue.

Traitement de la myasthénie auto-immune

Myasthenia gravis is the most common neuromuscular junction disorder and the best understood autoimmune disease of the nervous system. The autoimmune attack leads to decreased concentrations of the AChR and results in fatigability of skeletal muscles increasing with activity and improving with rest. The treatment of myasthenia has improved dramatically over the last few decades, with an increasing number of immunotherapies used in management although not all of them have been formally tested in double-blind, prospective trials. The principles of treatment consist in optimizing neuromuscular junction function by use of cholinesterase inhibitors, inducing an immunologic remission and then maintaining that remission by long-term immunotherapies. Prednisone and/or azathioprine are the most effective. Short-term immunotherapies, i.e. intravenous immunoglobulin or plasmapheresis, are indicated for disease exacerbation. For patients with nonthymomatous autoimmune myasthenia, the effectiveness of thymectomy remains uncertain. The overall objective of therapy is to enable patients to lead a normal life as rapidly as possible, while limiting side effects and costs if possible. Treatment should be individualized. The aggressiveness of therapy should be balanced against a number of factors including distribution of muscle involvement, rate of progression, degree of functional impairment, lifestyle choice, and coexisting disease. In all cases, adequate education, for the patient and the physician, is most helpful in facilitating management of this chronic disease.

Association of HLA-DQA1*0101/2 and DQB1*0502 with myasthenia gravis in southern Iranian patients.

Myasthenia gravis is an autoimmune disorder of neuromuscular junction characterized by skeletal muscle weakness and fatigability. Different genes may control the induction and clinical presentation of this disease. Various HLA alleles are reported as predisposing or protective genetic elements in myasthenia gravis. The aim of this study was to investigate the probable association between HLA-DQ alleles and myasthenia gravis in southern Iranian patients. HLA-DQA1 and DQB1 alleles were determined in 104 sporadic patients with myasthenia gravis using polymerase chain reaction - restriction fragment length polymorphism method and the results were compared to 816 healthy controls. HLA-DQA1*0101/2 (39.4%) and DQB1*0502 (21.6%) were the most frequent alleles in southern Iranian patients with myasthenia gravis. These alleles revealed positive associations with the disease with relative risks of 1.69 and 2.41, respectively. The most common haplotype was DQA1*0101/2-DQB1*0502 in these patients. According to the results of this study, DQA1*0101/2 and DQB1*0502 alleles might be considered as predisposing genetic factors to myasthenia gravis while DQA1*0501, DQB1*0301 and *0602/3 show protective roles against this disease.

Temporary fatigue and altered extracellular matrix in skeletal muscle during progression of heart failure in rats

Patients with congestive heart failure (CHF) experience increased skeletal muscle fatigue. The mechanism underlying this phenomenon is unknown, but a deranged extracellular matrix (ECM) might be a contributing factor. Hence, we examined ECM components and regulators in a rat postinfarction model of CHF. At various time points during a 3.5 mo-period after induction of CHF in rats by left coronary artery ligation, blood, interstitial fluid (IF), and muscles were sampled. Isoflurane anesthesia was employed during all surgical procedures. IF was extracted by wicks inserted intermuscularly in a hind limb. We measured cytokines in plasma and IF, whereas matrix metalloproteinase (MMP) activity and collagen content, as well as the level of glycosaminoglycans and hyaluronan were determined in hind limb muscle. In vivo fatigue protocols of the soleus muscle were performed at 42 and 112 days after induction of heart failure. We found that the MMP activity and collagen content in the skeletal muscles increased significantly at 42 days after induction of CHF, and these changes were time related to increased skeletal muscle fatigability. These parameters returned to sham levels at 112 days. VEGF in IF was significantly lower in CHF compared with sham-operated rats at 3 and 10 days, but no difference was observed at 112 days. We conclude that temporary alterations in the ECM, possibly triggered by VEGF, are related to a transient development of skeletal muscle fatigue in CHF.

Training Effects On Skeletal Muscle Calcium Handling In Chronic Heart Failure (CHF) Patients And Controls

CHF patients typically complain about increased skeletal muscle fatigability. This is not due to reduced skeletal muscle blood flow and seems to persist even after cardiac transplantation. We have previously reported that in contrast to normal muscle, reduced intracellular calcium release was not related to fatigue development in CHF rats (Lunde et al. Circ Res 98:1514, 2006). Therefore we hypothesize that training might affect intracellular calcium cycling differently in muscles from patients with CHF as compared with healthy controls (HS).

Decremental Response to High-Frequency Trains of Acetylcholine Pulses but Unaltered Fractional Ca2+ Currents in a Panel of “Slow-Channel Syndrome” Nicotinic Receptor Mutants

The slow-channel congenital myasthenic syndrome (SCCMS) is a disorder of the neuromuscular junction caused by gain-of-function mutations to the muscle nicotinic acetylcholine (ACh) receptor (AChR). Although it is clear that the slower deactivation time course of the ACh-elicited currents plays a central role in the etiology of this disease, it has been suggested that other abnormal properties of these mutant receptors may also be critical in this respect. We characterized the kinetics of a panel of five SCCMS AChRs (αS269I, βV266M, εL221F, εT264P, and εL269F) at the ensemble level in rapidly perfused outside-out patches. We found that, for all of these mutants, the peak-current amplitude decreases along trains of nearly saturating ACh pulses delivered at physiologically relevant frequencies in a manner that is consistent with enhanced entry into desensitization during the prolonged deactivation phase. This suggests that the increasingly reduced availability of activatable AChRs upon repetitive stimulation may well contribute to the fatigability and weakness of skeletal muscle that characterize this disease. Also, these results emphasize the importance of explicitly accounting for entry into desensitization as one of the pathways for burst termination, if meaningful mechanistic insight is to be inferred from the study of the effect of these naturally occurring mutations on channel function. Applying a novel single-channel–based approach to estimate the contribution of Ca2+ to the total cation currents, we also found that none of these mutants affects the Ca2+-conduction properties of the AChR to an extent that seems to be of physiological importance. Our estimate of the Ca2+-carried component of the total (inward) conductance of wild-type and SCCMS AChRs in the presence of 150 mM Na+, 1.8 mM Ca2+, and 1.7 mM Mg2+ on the extracellular side of cell-attached patches turned out be in the 5.0–9.4 pS range, representing a fractional Ca2+ current of ∼14%, on average. Remarkably, these values are nearly identical to those we estimated for the NR1-NR2A N-methyl-d-aspartate receptor (NMDAR), which has generally been considered to be the main neurotransmitter-gated pathway of Ca2+ entry into the cell. Our estimate of the rat NMDAR Ca2+ conductance (using the same single-channel approach as for the AChR but in the nominal absence of extracellular Mg2+) was 7.9 pS, corresponding to a fractional Ca2+ current of 13%.

NeuroSurgery in a Symptomatic Myasthenia Gravis Patient

Myasthenia gravis is an autoimmune disease characterized by weakness and fatigability of skeletal muscles, with improvement following rest. It may be localized to specific muscle groups or it may be generalized. The preoperative management of a patient with myasthenia gravis poses a significant challenge to the anesthesiologist. In this report, we present the case of a symptomatic myasthenia patient who underwent a neurosurgical procedure successfully. An attempt to estimate neuromuscular blockade after the administration of non depolarizing relaxants to anaesthetized myasthenic patients is described.

Impact of varying pulse frequency and duration on muscle torque production and fatigue

Neuromuscular electrical stimulation (NMES) involves the use of electrical current to facilitate contraction of skeletal muscle. However, little is known concerning the effects of varying stimulation parameters on muscle function in humans. The purpose of this study was to determine the extent to which varying pulse duration and frequency altered torque production and fatigability of human skeletal muscle in vivo. Ten subjects underwent NMES-elicited contractions of varying pulse frequencies and durations as well as fatigue tests using stimulation trains of equal total charge, yet differing parametric settings at a constant voltage. Total charge was a strong predictor of torque production, and pulse trains with equal total charge elicited identical torque output. Despite similar torque output, higher- frequency trains caused greater fatigue. These data demonstrate the ability to predictably control torque output by simultaneously controlling pulse frequency and duration and suggest the need to minimize stimulation frequency to control fatigue.

Possible use of repeated cold stress for reducing fatigue in chronic fatigue syndrome: a hypothesis

BackgroundPhysiological fatigue can be defined as a reduction in the force output and/or energy-generating capacity of skeletal muscle after exertion, which may manifest itself as an inability to continue exercise or usual activities at the same intensity. A typical example of a fatigue-related disorder is chronic fatigue syndrome (CFS), a disabling condition of unknown etiology and with uncertain therapeutic options. Recent advances in elucidating pathophysiology of this disorder revealed hypofunction of the hypothalamic-pituitary-adrenal axis and that fatigue in CFS patients appears to be associated with reduced motor neurotransmission in the central nervous system (CNS) and to a smaller extent with increased fatigability of skeletal muscle. There is also some limited evidence that CFS patients may have excessive serotonergic activity in the brain and low opioid tone.Presentation of the hypothesisThis work hypothesizes that repeated cold stress may reduce fatigue in CFS because brief exposure to cold may transiently reverse some physiological changes associated with this illness. For example, exposure to cold can activate components of the reticular activating system such as raphe nuclei and locus ceruleus, which can result in activation of behavior and increased capacity of the CNS to recruit motoneurons. Cold stress has also been shown to reduce the level of serotonin in most regions of the brain (except brainstem), which would be consistent with reduced fatigue according to animal models of exercise-related fatigue. Finally, exposure to cold increases metabolic rate and transiently activates the hypothalamic-pituitary-adrenal axis as evidenced by a temporary increase in the plasma levels of adrenocorticotropic hormone, beta-endorphin and a modest increase in cortisol. The increased opioid tone and high metabolic rate could diminish fatigue by reducing muscle pain and accelerating recovery of fatigued muscle, respectively.Testing the hypothesisTo test the hypothesis, a treatment is proposed that consists of adapted cold showers (20 degrees Celsius, 3 minutes, preceded by a 5-minute gradual adaptation to make the procedure more comfortable) used twice daily.Implications of the hypothesisIf testing supports the proposed hypothesis, this could advance our understanding of the mechanisms of fatigue in CFS.

Skeletal muscle contractility is preserved in COPD patients with normal fat‐free mass

Peripheral muscle dysfunction often occurs in patients with chronic obstructive pulmonary disease (COPD). The muscle dysfunction may be caused by a loss of force-generating capacity, resulting from a loss of muscle mass, as well as by other alterations in contractile properties of skeletal muscle. The maximal isometric voluntary strength and fatigability were determined in hand-grip and quadriceps muscles from nine male COPD patients (FEV(1) 30-50% predicted) and control subjects matched for fat-free mass (FFM), physical activity level and age. Contractile properties and fatigability of the quadriceps muscle were also studied with electrically evoked isometric contractions. The maximal voluntary force (MVC) and fatigability of the handgrip muscle did not differ between the COPD patients and control subjects. Also the MVC of the quadriceps muscle and the rate of force rise, contraction time, force-frequency relationship and fatigability, as determined with electrically evoked contractions, were similar in patients with COPD and control subjects. Skeletal muscle strength, contractile properties and fatigability are preserved in patients with moderate COPD and a normal FFM and activity level. This suggests that skeletal muscle dysfunction does not take place during moderate COPD until cachexia and/or a decline in physical activity occur.

Gender Differences In Muscle Strength , Blood Flow And Oxygen Consumption Recovery From Intermittent Handgrip Exercise

Several studies have suggested that women may have greater resistance to skeletal muscle fatigue than men. Blood flow and oxygen consumption in working muscles are critical factors for muscle performance, fatigue-resistance, and muscle strength recovery from exercise. However, the mechanisms causing gender differences in muscle strength recovery from exercise are unclear. PURPOSE To investigate a mechanism causing gender differences in skeletal muscle fatigability, we examined whether there is a difference in muscle blood flow and oxygen consumption after intermittent handgrip exercise between men and women using near-infrared spectroscopy (NIRS) and high resolution ultrasound system. METHODS Healthy young (24.6±2.8 years) men (n =5) and women (n =5) laid supine and repeated static contractions of handgrip muscles at 100% maximal voluntary contraction (MVC) for 5 seconds followed by 5 seconds rest for 4 minutes. The MVC force was measured before, each minute during, and 2, 5, and 10 minute after the end of the exercise. We measured total-and deoxy-hemoglobin/myoglobin level by venous occlusion NIRS method, and calculated O2 supply index (OSI) and O2 consumption index (OCI), as follows OSI=[d(total Hb/Mb)/dt]·SaO2±100−1(OD/ min), OCI=[d(deoxy Hb/Mb)/dt]-[d(total Hb/Mb)/dt]·(1-SaO 2)·100−1(OD/min). The % MVC, %OSI, and %OCI were calculated as relative changes to the pre-exercise values. Simultaneously, forearm blood flow (FBF) was measured by a high resolution ultrasound system. RESULTS No gender difference was found in MVC force decline during the exercise. However, the force recovery was significantly faster in women than in men at minutes 5 (80.8±6.1 vs. 66.3±12.7 %MVC, p < 0.05) and 10 (86.0±5.8 vs. 71.8±11.7 %MVC, p < 0.05) of recovery. The %OSI was significantly lower in women than in men at minutes 5 (128.0±28.7 vs. 177.8±23.5 %OSI, p < 0.05) and 10 (111.2±8.3 vs. 156.1±39.7 %OSI, p < 0.05) of recovery, but no significant effects of gender were detected in %OCI. Although absolute FBF was less in women than in men before and after the exercise, %FBF was not different between groups. Furthermore, %MVC of recovery tended to correlate with %OCI of recovery in women (r=0.548, p=0.077), but not in men. CONCLUSION These findings suggest that women recovered their strength faster after intermittent handgrip exercise compared with men, and the observed differences that women more effectively consumed oxygen supplied to the working muscles may be linked with the underlying mechanisms causing gender differences in skeletal muscle fatigability.

Gender Differences In Muscle Strength , Blood Flow And Oxygen Consumption Recovery From Intermittent Handgrip Exercise

Several studies have suggested that women may have greater resistance to skeletal muscle fatigue than men. Blood flow and oxygen consumption in working muscles are critical factors for muscle performance, fatigue-resistance, and muscle strength recovery from exercise. However, the mechanisms causing gender differences in muscle strength recovery from exercise are unclear. PURPOSE To investigate a mechanism causing gender differences in skeletal muscle fatigability, we examined whether there is a difference in muscle blood flow and oxygen consumption after intermittent handgrip exercise between men and women using near-infrared spectroscopy (NIRS) and high resolution ultrasound system. METHODS Healthy young (24.6±2.8 years) men (n =5) and women (n =5) laid supine and repeated static contractions of handgrip muscles at 100% maximal voluntary contraction (MVC) for 5 seconds followed by 5 seconds rest for 4 minutes. The MVC force was measured before, each minute during, and 2, 5, and 10 minute after the end of the exercise. We measured total-and deoxy-hemoglobin/myoglobin level by venous occlusion NIRS method, and calculated O2 supply index (OSI) and O2 consumption index (OCI), as follows OSI=[d(total Hb/Mb)/dt]·SaO2±100−1(OD/ min), OCI=[d(deoxy Hb/Mb)/dt]-[d(total Hb/Mb)/dt]·(1-SaO 2)·100−1(OD/min). The % MVC, %OSI, and %OCI were calculated as relative changes to the pre-exercise values. Simultaneously, forearm blood flow (FBF) was measured by a high resolution ultrasound system. RESULTS No gender difference was found in MVC force decline during the exercise. However, the force recovery was significantly faster in women than in men at minutes 5 (80.8±6.1 vs. 66.3±12.7 %MVC, p < 0.05) and 10 (86.0±5.8 vs. 71.8±11.7 %MVC, p < 0.05) of recovery. The %OSI was significantly lower in women than in men at minutes 5 (128.0±28.7 vs. 177.8±23.5 %OSI, p < 0.05) and 10 (111.2±8.3 vs. 156.1±39.7 %OSI, p < 0.05) of recovery, but no significant effects of gender were detected in %OCI. Although absolute FBF was less in women than in men before and after the exercise, %FBF was not different between groups. Furthermore, %MVC of recovery tended to correlate with %OCI of recovery in women (r=0.548, p=0.077), but not in men. CONCLUSION These findings suggest that women recovered their strength faster after intermittent handgrip exercise compared with men, and the observed differences that women more effectively consumed oxygen supplied to the working muscles may be linked with the underlying mechanisms causing gender differences in skeletal muscle fatigability.