Contractile Fatigue Research Articles

Reactive oxygen species: impact on skeletal muscle.

It is well established that contracting muscles produce both reactive oxygen and nitrogen species. Although the sources of oxidant production during exercise continue to be debated, growing evidence suggests that mitochondria are not the dominant source. Regardless of the sources of oxidants in contracting muscles, intense and prolonged exercise can result in oxidative damage to both proteins and lipids in the contracting myocytes. Further, oxidants regulate numerous cell signaling pathways and modulate the expression of many genes. This oxidant-mediated change in gene expression involves changes at transcriptional, mRNA stability, and signal transduction levels. Furthermore, numerous products associated with oxidant-modulated genes have been identified and include antioxidant enzymes, stress proteins, and mitochondrial electron transport proteins. Interestingly, low and physiological levels of reactive oxygen species are required for normal force production in skeletal muscle, but high levels of reactive oxygen species result in contractile dysfunction and fatigue. Ongoing research continues to explore the redox-sensitive targets in muscle that are responsible for both redox regulation of muscle adaptation and oxidant-mediated muscle fatigue.

Taurine supplementation increases skeletal muscle force production and protects muscle function during and after high-frequency in vitro stimulation

Recent studies report that depletion and repletion of muscle taurine (Tau) to endogenous levels affects skeletal muscle contractility in vitro. In this study, muscle Tau content was raised above endogenous levels by supplementing male Sprague-Dawley rats with 2.5% (wt/vol) Tau in drinking water for 2 wk, after which extensor digitorum longus (EDL) muscles were examined for in vitro contractile properties, fatigue resistance, and recovery from fatigue after two different high-frequency stimulation bouts. Tau supplementation increased muscle Tau content by approximately 40% and isometric twitch force by 19%, shifted the force-frequency relationship upward and to the left, increased specific force by 4.2%, and increased muscle calsequestrin protein content by 49%. Force at the end of a 10-s (100 Hz) continuous tetanic stimulation was 6% greater than controls, while force at the end of the 3-min intermittent high-frequency stimulation bout was significantly higher than controls, with a 12% greater area under the force curve. For 1 h after the 10-s continuous stimulation, tetanic force in Tau-supplemented muscles remained relatively stable while control muscle force gradually deteriorated. After the 3-min intermittent bout, tetanic force continued to slowly recover over the next 1 h, while control muscle force again began to decline. Tau supplementation attenuated F(2)-isoprostane production (a sensitive indicator of reactive oxygen species-induced lipid peroxidation) during the 3-min intermittent stimulation bout. Finally, Tau transporter protein expression was not altered by the Tau supplementation. Our results demonstrate that raising Tau content above endogenous levels increases twitch and subtetanic and specific force in rat fast-twitch skeletal muscle. Also, we demonstrate that raising Tau protects muscle function during high-frequency in vitro stimulation and the ensuing recovery period and helps reduce oxidative stress during prolonged stimulation.

Effect of expiratory resistive loading on inspiratory and expiratory muscle fatigue

Inspiratory and expiratory pressures are increased during expiratory resistive loading (ERL). We asked whether ERL elicits inspiratory as well as expiratory muscle fatigue. On four separate days, seven male subjects underwent ERL to task failure. Subjects maintained respiratory frequency at 15 breaths min(-1), expiratory gastric pressure at 40% or 60% of maximum, and expiratory duty cycle at 0.4 or 0.7 (ERL(40%0.4), ERL(40%0.7), ERL(60%0.4), ERL(60%0.7)). Inspiratory and abdominal muscle contractility was assessed before and up to 30 min after ERL by measuring transdiaphragmatic twitch pressure (P(di,tw)) and gastric twitch pressure (P(ga,tw)) in response to magnetic nerve stimulation. After each trial, P(di,tw) and P(ga,tw) were reduced below baseline values (-9 to -15% for P(di,tw) and -15 to -22% for P(ga,tw); P<0.05). The severity of diaphragm fatigue was unaffected by expiratory pressure production or expiratory duty cycle, whereas extending the expiratory duty cycle increased the severity of abdominal muscle fatigue. In conclusion, ERL elicits contractile fatigue of the diaphragm and the abdominal muscles.

Fatigue‐induced changes in tonic vibration response (TVR) in humans: Relationships between electromyographic and biochemical events

Fatigue-induced changes in the proprioceptive reflex loop were explored in humans by using the tonic electromyographic (EMG) response to vibration (TVR) and relating it to lactic acidosis (LA) and oxidative stress. TVR was measured in flexor digitorum superficialis before and after sustained or intermittent handgrip at maximal voluntary contraction (MVC). TVR variations were compared with the changes in EMG power spectrum preceding contractile fatigue, the Hoffman reflex (H-reflex), and plasma concentrations of LA and thiobarbituric acid reactive substances (TBARS). After both sustained and intermittent handgrips, TVR amplitude first declined then increased, independently from the changes in EMG power spectrum and H-reflex. TVR depression and facilitation were respectively concomitant with increases in LA and TBARS. The TVR depression was proportional to the increased LA level. The origin of TVR changes after muscle fatigue is questioned because the relationship between TVR depression and LA accumulation might be temporal, not causal, and changes in muscle stiffness were not explored.

Development of respiratory muscle contractile fatigue in the course of hyperpnoea

To assess the development of inspiratory and expiratory muscle fatigue during normocapnic hyperpnoea, we studied fourteen healthy men performing 8min hyperpnoea, 6min pause, 8min hyperpnoea, etc., until task failure. Twitch transdiaphragmatic (P(di,tw)) and gastric (P(ga,tw)) pressures were measured during cervical and thoracic magnetic nerve stimulation, before hyperpnoea, after every 8min of hyperpnoea, and at task failure (i.e., at 25.3+/-4.7min). P(di,tw) decreased during the first 16min (-28+/-7%, p<0.001) and P(ga,tw) during the first 8min (-20+/-7%, p<0.001) of hyperpnoea without further change until task failure. During inspiration, the pressure-time-product of oesophageal pressure (PTP(oes)) increased relative to PTP(di) during the first 16min (+11+/-21%, p<0.05). Similarly, during expiration, PTP(oes) increased relative to PTP(ga) during the first 8min (+10+/-16%, p<0.05). Also, blood lactate concentration and respiratory sensations significantly increased during the first 8min (+1.0+/-0.5mmoll(-1), p<0.001) and 16min (breathlessness +1.6+/-1.8 points, respiratory effort +5.9+/-2.2points, p<0.001), respectively. We conclude that, during hyperpnoea, contractile fatigue of the diaphragm and abdominal muscles develops long before task failure and may trigger an increased recruitment of rib cage muscles.

Sex differences in contractile properties and fatigue resistance of human skeletal muscle

To explore the cause of higher skeletal muscle fatigue resistance in women than men, we used electrically evoked contractions (1 s on, 1 s off, 30 Hz, 2 min), which circumvent motivational bias and allow examination of contractile properties. We compared 29 men [26.5 (7.0) years old; mean (s.d.)] with 35 women [25.4 (7.6) years old]. Strength of the quadriceps muscle was higher in men than women (P < 0.001). The lower maximal rate of relaxation in women (P = 0.002) indicates that their muscles were slower than those of men. The torque declined less in women than in men [37.7 (10.7) versus 29.9 (10.0)%; P = 0.002], and was not related to muscle strength or size, as determined with magnetic resonance imaging. The sex difference in fatigability was also seen when the circulation to the leg was occluded [torque declined 76.9 (10.8) versus 59.5 (16.9)% in men versus women, respectively; P = 0.008]. The maximal rate of relaxation correlated with the fatigability of the muscle under all conditions (correlations ranging from 0.34 to 0.51, P < 0.02). We conclude that the sex-related difference in skeletal muscle fatigue resistance is not explicable by differences in motivation, muscle size, oxidative capacity and/or blood flow between sexes, but might be related to differences in fibre type composition.

Creatine Supplementation Augments Skeletal Muscle Carnosine Content in Senescence-Accelerated Mice (SAMP8)

The histidine-containing dipeptides (HCD) carnosine and anserine are found in high concentrations in mammalian skeletal muscle. Given its versatile biologic properties, such as antioxidative, antiglycation, and pH buffering capacity, carnosine has been implicated as a protective factor in the aging process. The present study aimed to systematically explore age-related changes in skeletal muscles HCD content in a murine model of accelerated aging. Additionally, we investigated the effect of lifelong creatine supplementation on muscle HCD content and contractile fatiguability. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 weeks. At week 10, 25, and 60, tibialis anterior muscles were dissected and analysed for HCD and taurine content by HPLC. Soleus and EDL muscles were tested for in vitro contractile fatigue and recovery. From 10 to 60 weeks of age, muscular carnosine (-45%), taurine (-24%), and total creatine (-42%) concentrations gradually and significantly decreased. At 25 but not at 60 weeks, oral creatine supplementation significantly increased carnosine (+88%) and anserine (+40%) content compared to age-matched control-fed animals. Taurine and total creatine content were not affected by creatine supplementation at any age. Creatine-treated mice showed attenuated muscle fatigue (soleus) and enhanced force recovery (m. extensor digitorum longus [EDL]) compared to controls at 25 weeks, but not at 60 weeks. From the present study, we can conclude that skeletal muscle tissue exhibits a significant decline in HCD content at old age. Oral creatine supplementation is able to transiently but potently increase muscle carnosine and anserine content, which coincides with improved resistance to contractile fatigue.

Locus of Symptom Limitation and Exercise Response to Bronchodilation in Chronic Obstructive Pulmonary Disease

To evaluate the concordance between subjective and objective indices of muscle fatigue during exercise and to assess the significance of the perception of dyspnea and leg fatigue for the exercise response to bronchodilation in chronic obstructive pulmonary disease (COPD). Sixty-eight patients with COPD performed either 2 constant work-rate cycling exercises or 2 endurance shuttle walking tests. These tests were preceded by nebulization of placebo or 500 mug of ipratropium bromide. Changes in forced expiratory volume in 1 second and in endurance time with bronchodilation were measured. Changes in quadriceps twitch force after exercise were evaluated. In addition, the locus of symptom limitation was assessed. Patients who stopped exercising because of leg fatigue showed a larger fall in quadriceps twitch force in comparison with patients who stopped for dyspnea. The proportion of patients who developed contractile fatigue of the quadriceps (postexercise fall in quadriceps twitch force >15% resting value) was substantially smaller in patients stopping exercise because of dyspnea than in those stopping because of leg fatigue or a combination of the 2 symptoms. The locus of symptom limitation modulated the exercise response to bronchodilation; patients stopping exercise because of leg fatigue or a combination of dyspnea/leg fatigue showed a smaller improvement in endurance time to constant work-rate exercise with bronchodilation compared with those stopping because of dyspnea. Patients with COPD reporting leg fatigue as the main exercise-limiting symptom had a smaller increase in endurance time to constant work-rate exercise after bronchodilation compared with those reporting dyspnea as the main limiting symptom.

Serum LDH and exercise capacity in COPD

Lactate dehydrogenase (LDH) is the enzyme that catalyses the final step in the glycolytic metabolism, regenerating NAD+ from reduced NADH, by conversion of pyruvate to lactate.1 Recently, increased muscle LDH...

Metabolic and functional effects of glutamate intake in patients with chronic obstructive pulmonary disease (COPD)

Patients with chronic obstructive pulmonary disease (COPD) often suffer from skeletal muscle weakness due to muscle wasting and altered muscle metabolism. Decreased muscle glutamate concentration in COPD is consistently reported and is associated with decreased muscle glutathione concentration and early lactic acidosis. We hypothesized that an increased availability of glutamate via glutamate ingestion increases muscle glutamate concentration leading to acute improvements in skeletal muscle energy metabolism and function. Two experiments were conducted. In experiment 1, in two groups of 6 male COPD patients (FEV(1): 44.8+/-3.4%pred) and 6 healthy controls, blood samples and muscle biopsies were taken at 0 and 80 min after repeated glutamate (30 mg/kg BW) or control ingestion (1.25 ml/kg BW), and after 20 min cycling at 50% peak workload. In experiment 2, in 10 COPD patients (FEV(1): 36.1+/-2.5%pred), the effect of the two drinks was tested on cycle endurance time and contractile quadriceps fatigue measured by magnetic stimulation before and after cycling at 75% peak workload. Glutamate ingestion increased plasma (p<0.01) but not muscle glutamate concentration. Muscle total and reduced glutathione and plasma lactate concentration were not affected by glutamate ingestion. Glutamate ingestion did not influence contractile muscle fatigue and endurance time. Continuous oral glutamate ingestion for 80 min did not lead to an acute effect on skeletal muscle substrate metabolism and muscle performance in COPD patients and in age-matched healthy controls.

Effect of beta2-adrenoceptor stimulation on contractile properties and fatigue recovery in senescent rats

Effect of beta2-adrenoceptor stimulation on contractile properties and fatigue recovery in senescent rats

Locus of Symptom Limitation and Exercise Response to Bronchodilation in Chronic Obstructive Pulmonary Disease

Background: We previously reported that the occurrence of contractile fatigue of the quadriceps during exercise in patients with COPD reduced the likelihood of acute bronchodilation to improve the endurance time to constant work rate exercise. The purpose of the present study was to assess whether the perception of dyspnea and leg fatigue during exercise could be used to predict the exercise response to acute bronchodilation in this population. &#x0D; &#x0D; Methods: Sixty-eight patients with COPD performed either two constant work-rate cycling exercises or two endurance shuttle walking tests. These tests were preceded by nebulization of placebo or 500 mg ipratropium bromide. Changes in FEV1 and in the endurance time with bronchodilation were measured. The changes in quadriceps twitch force after exercise were evaluated. In addition, we assessed dyspnea and perception of leg fatigue on Borg scale as well as the locus of exercise limitation (dyspnea, leg fatigue, or both).&#x0D; &#x0D; Results: The locus of symptom limitation was useful to predict the exercise response to bronchodilation; patients stopping exercise because of leg fatigue or due to a combination of dyspnea/leg fatigue showed a smaller improvement in endurance time to constant work rate exercise with bronchodilation compared with those stopping because of dyspnea. Subjective and objective evidences of fatigue were related: patients who stopped exercising because of leg fatigue showed a larger fall in quadriceps twitch force compared to patients who stopped for dyspnea. &#x0D; &#x0D; Conclusion: The assessment of the locus of symptom limitation during constant work rate exercise is useful to predict the improvement in endurance time following acute bronchodilation in patients with COPD.

Susceptibility to Muscle Fatigue and Lung Mechanics in Chronic Obstructive Pulmonary Disease

Background: Contractile fatigue of the quadriceps occurs in a significant proportion of patients with COPD after constant-load cycling exercise. Dynamic hyperinflation, by altering cardiac output during exercise, could contribute to fatigue susceptibility in this population. The purpose of this study was to compare operational lung volumes during constant workrate exercise between COPD patients who do and those who do not develop contractile fatigue of the quadriceps (fatiguers vs non-fatiguers).&#x0D; &#x0D; Methods: Sixty-two patients with COPD (FEV1: 46±16%) completed a constant-load cycling test at 80% of the peak workrate achieved during progressive cycle ergometry. Ventilatory parameters were monitored breath-by-breath, while inspiratory capacity maneuvers were obtained every other minute during constant-load cycling. Quadriceps twitch force was measured with magnetic stimulation of the femoral nerve before and after the test. Muscle fatigue was defined as a post-exercise reduction in quadriceps twitch force of more than 15% of the resting value.&#x0D; &#x0D; Results: Forty patients (65%) developed muscle fatigue after constant-load cycling. No significant differences were found between fatiguers and non-fatiguers with respect to age, body mass index, resting lung function, peak oxygen consumption, and endurance time to constant-load exercise. Change in inspiratory capacity from rest to end-exercise (DIC) was similar between both subgroups (DIC: 0.56±0.32L vs 0.56±0.47L for fatiguers and non-fatiguers respectively, P=0.99).&#x0D; &#x0D; Conclusion: Susceptibility to muscle fatigue could not be predicted by exercise duration or by the degree of dynamic hyperinflation in patients with COPD.

Assessment of the reliability of central and peripheral fatigue after sustained maximal voluntary contraction of the quadriceps muscle

The aim of the present study was to further confirm the validity of measurements for characterizing neuromuscular alterations by establishing their reliability both before and after fatigue. Thirteen men (28 +/- 5 years) volunteered to participate in two separate identical sessions requiring the performance of a sustained maximal voluntary contraction (MVC) with the quadriceps muscle for 2 min. MVC and transcutaneous electrical stimulations were used before and immediately after the fatiguing contraction to investigate the reliability of MVC torque, central activation, and peripheral variables (M-wave properties, peak twitch, peak doublet) within and between sessions. Based on previous and present results, we advise the use of (1) voluntary activation level with potentiated doublet as a reference to describe central fatigue, (2) electromyographic activity of vastus lateralis muscle as a surrogate for quadriceps for both voluntary and evoked contraction, and (3) potentiated peak doublet amplitude to investigate contractile fatigue. These findings can be useful in the choice of the parameters describing central and peripheral fatigue of the quadriceps muscle in future studies.

Heliox Delays Exercise Dynamic Hyperinflation and Leg Muscle Fatigue in Ventilatory Limited Patients with COPD

PURPOSE: Patients with COPD exhibit exercise intolerance that is due to dynamic hyperinflation or leg muscle fatigue, but it is unknown how these exercise limitations interact. We hypothesized that, by delaying dynamic hyperinflation with heliox, exercise tolerance and leg muscle fatigue would increase in patients limited by ventilation, and not in those limited by leg muscle fatigue. METHODS: Eleven patients with COPD (FEV1 52 ± 17% predicted, VO2max 14 ± 4.6 ml/kg/min) completed two randomized exercise bouts at 80% of peak power output on a cycle ergometer breathing either room air or heliox (21% O2, 79% He) and one exercise bout breathing heliox but stopping at isotime on the room air test. Exercising end-expired lung volume was determined from inspiratory capacity (IC). Contractile leg muscle fatigue was determined by direct motor point magnetic stimulation to obtain vastus lateralis potentiated twitch prior to exercise and at 5, 10, and 20 minutes post exercise. Patients were grouped into fatiguers (F; 5 minute potentiated twitch (5PT) ≤ 85% of pre exercise value on the room air test) and non fatiguers (NF). RESULTS: Seven of the 11 patients were NF (5PT 93 ± 4.9%) and increased their exercise endurance time while breathing heliox from 355 ± 203 to 610 ± 317s (P < 0.001) while exercise endurance time did not change in the four F (5PT 74 ± 6.9%). At end exercise, the NF had a lower IC on both the room air and heliox tests (1.47 ± 0.38 L and 1.57 ± 0.50 L vs. 2.23 ± 0.41 L and 2.58 ± 0.30 L, respectively; P < 0.01) and reached a higher end inspiratory lung volume (EILV; 96.6 ± 2.2 and 96.6 ± 2.2% vs. 92.6 ± 4.2 and 88.7 ± 5.9%, respectively, P < 0.05). The increased exercise time with heliox in the NF resulted in a greater level of muscle fatigue (5PT decreased to 73.6 ± 6.4%; P < 0.001). At isotime with heliox, the NF group demonstrated an increased IC (1.89 ± 0.59 L), a lower EILV (93.3 ± 3.7%) and a similar level of muscle fatigue (89.8 ± 5.5%)(P < 0.05). The change in exercise time was most highly correlated with room air 5PT (r = 0.79, P <.01) and EILV (r = 0.68, P < 0.05) and there was a significant association between room air 5PT and EILV (r = −0.77, P < 0.01) indicating that patients with the least amount of muscle fatigue were more ventilatory limited and had a greater response to breathing heliox. CONCLUSIONS: The ability to decrease exercise hyperinflation with heliox in patients with COPD depends on the relative contributions of ventilatory and leg muscle limitations during cycling exercise. Heliox was less effective in improving exercise tolerance in patients limited by leg fatigue, suggesting that targeted leg muscle rehabilitation may be more beneficial in these patients.

A novel mouse skeletal muscle-nerve preparation and in vitro model of ischemia

The majority of patients in pain clinics are treated for muscle pain yet methods to study it in animals are relatively weak compared to methods to study skin pain. Here we describe an in vitro muscle-nerve preparation and model of muscle ischemia and contractile fatigue in mice. Timed muscle contraction is electrically evoked, while single unit activity of muscle sensory neurons and muscle contractile force are simultaneously recorded. The muscle is placed in a small (<1 mL) chamber where oxygen levels can be manipulated, drugs can be applied, and the extracellular milieu can be highly controlled. We demonstrate that we can record from sensory afferents that have the properties expected of ischemic nociceptors. This method serves for studying the neuronal and molecular mechanisms underlying ischemic pains such as angina, intermittent claudication, and sickle cell crisis.

Physiological fatigue of smooth muscle contractions in rat urinary bladder

To characterize the physiological fatigue in bladder smooth muscles that can occur within 60 s of stimulation, which is closer to the duration of normal voiding. Longitudinal and transverse strips of rat bladder were used; the muscles were mounted in an in vitro multi-muscle chamber, and the decline in contractile tension recorded during continuous electrical stimulation at frequencies of 5-30 Hz for 60 s. The effect of muscle length on fatigue was assessed by monitoring the decline in tension during 30 Hz stimulation at rest length, and at 60% and 100% stretched lengths of the bladder strips. To assess some of the factors involved in the development of fatigue, tension responses of fatigued muscles were monitored on exposure to 80 mm potassium or 1 microm bethanechol. In both longitudinal and transverse bladder strips stimulated at 30 Hz, peak contractile tension declined to 50% of original after approximately 33 s, and to 30% after 60 s of stimulation. After 10 s rest, 60% of the original tension was recovered. Increasing the frequency of fatigue stimulation from 5 to 30 Hz significantly increased the extent of the decline in tension and reduced the time to a 50% decrease in tension. Stretching the bladder strips from rest length to 100% stretched length significantly reduced the extent of tension decline and increased the time to a 50% decrease in tension. Exposure of fatigued muscles to high potassium or bethanechol generated more tension than electrical stimulation. Contractile fatigue occurs in both longitudinal and transverse strips of the bladder smooth muscles within the duration of normal voiding. Increasing the frequency of stimulation from 5 to 30 Hz increased the degree and rate of fatigue. Stretching the bladder strips from rest length by 60-100% reduced the degree and rate of fatigue. Bladder fatigue may be caused by decreased depolarization of the smooth muscle membranes, reduced release of acetylcholine from presynaptic nerve terminals, or by other yet undetermined mechanisms.

The effect of taurine depletion on the contractile properties and fatigue in fast-twitch skeletal muscle of the mouse

Taurine increases force production in skeletal muscle, and taurine levels may fall during exercise. The contractile properties and fatigability of extensor digitorum longus (EDL) muscles depleted of taurine by guanodinoethane sulfonate (GES) treatment were investigated. GES treatment decreased muscle taurine levels to <40% of controls. Peak twitch force levels were 23% of controls in GES treated EDL muscles (p < 0.05), but maximal specific force was unaffected. The force-frequency relationship was examined and significantly less force was produced by the GES treated muscles compared to controls at stimulation frequencies from 50 to 100 Hz (p < 0.05). GES treated EDL muscles exhibited significantly slower rates of fatigue than controls (p < 0.05). In skinned fibres, 20 mM GES had a small but significant effect on force production, indicating that GES may have some minor taurine-like effects. In this study, a fall in taurine levels decreased force output, and increased the endurance of EDL skeletal muscles.

Assessment of muscle fatigue during exercise in chronic obstructive pulmonary disease

Contractile fatigue is associated with exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Contractile fatigue may be assessed by quantifying the decline in strength after a fatiguing protocol but this may pose practical problems. The purpose of this study was to investigate the relationship between the decline in quadriceps strength, quadriceps electrical activity, perception of leg fatigue, and arterial lactate level in patients with COPD during constant work-rate cycling exercise. The decline in quadriceps strength was significantly associated with the decrease in electromyographic median frequency (r = 0.606), leg fatigue perception (r = 0.453), and arterial lactate level (r = 0.384). Using the receiver-operating-characteristic curve, it was found that a 4% decline in electromyographic median frequency had a 94% sensitivity and a 75% specificity to predict contractile fatigue. We conclude that contractile fatigue commonly occurs during cycling exercise in COPD. The electromyographic median frequency appears to be a valuable indirect marker to predict contractile leg fatigue.

Acute hypoxia limits endurance but does not affect muscle contractile properties

Acute hypoxia causes skeletal muscle dysfunction in vitro, but little is known about its effect on muscle function in vivo. In 10 healthy male subjects, isometric contractile properties and fatigue resistance of the quadriceps muscle were determined during normoxia and hypoxia using electrically evoked and voluntary contractions. The oxygen saturation (SaO(2); 96.9 +/- 0.7 vs. 79.9 +/- 3.0%; P < 0.001) was reduced during hypoxia. The maximal voluntary contraction (MVC), force-frequency relation, and contraction and relaxation times were unaffected by hypoxia. The endurance time of a sustained 30% MVC was reduced in hypoxia (248 +/- 104 vs. 217 +/- 76 s; P < 0.05), but not that of a sustained 70% MVC. Fatigue induced by electrically evoked intermittent contractions was unaltered. Thus, acute hypoxia has no significant impact on contractile properties of skeletal muscle in vivo but causes reduced endurance during low-level sustained voluntary contractions. This indicates that skeletal muscle dysfunction during conditions associated with prolonged hypoxemia, except for limited endurance, is not due to acute effects of hypoxemia.