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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of exercise (swimming), fatigue, and recovery on the intracellular pH (pHi), energy-rich phosphates, and related metabolites were studied in the gastrocnemius muscle of common frogs (Rana temporaria) at 20 degrees C. Exercise caused a rapid decrease in the content of phosphocreatine (PCr) and a corresponding increase in that of Pi. The ATP level remained virtually constant for 1 min; its precipitous decrease during the following minute was associated with a rise in the contents of inosine 5'-monophosphate (IMP) and NH4+, indicating a marked activation of AMP deaminase. Five minutes of swimming caused severe fatigue, which was correlated with decreases in muscle PCr (-85%), ATP (-42%), and pHi (-0.8 units). Recovery appeared almost complete within 2 h, and the frogs were then induced to swim again. During the initial 10 s of this second exercise, ATP synthesis was as high as in the first exercise, but the rate decreased more rapidly between 10 and 60 s, thus indicating that repeated exercise caused increased metabolic stress. IMP formation in working muscle was not strictly correlated with the pHi or the tissue contents of Pi, AMP and ADP, although from studies in vitro AMP deaminase is known to be modulated by these parameters.
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PMID:Exercise and recovery in frog muscle: metabolism of PCr, adenine nucleotides, and related compounds. 896 11

During fatigue, muscles become weaker, slower, and more economical at producing tension. Studies of skinned muscle fibers can explain some but not all of these effects, and, in particular, they are less economical in conditions that simulate fatigue. We investigated three factors that may contribute to the different behavior of skinned fibers. 1) Skinned fibers have increased myofilament lattice spacing, which is reversible by osmotic compression. 2) A myosin subunit becomes phosphorylated during fatigue. 3) Inosine 5'-monophosphate (IMP) accumulates during fatigue. We tested the response of phosphorylated and unphosphorylated single skinned fibers (isometric tension, contraction velocity, and adenosinetriphosphatase activity) to changes in lattice spacing (0-5% dextran) and IMP (0-5 mM) in the presence of altered concentrations of P(i) (3-25 mM), H+ (pH 7-6.2), and ADP (0-5 mM). The response of maximally activated skinned fibers to the direct metabolites of ATP hydrolysis is not altered by osmotic compression, phosphorylating myosin subunits, or increasing IMP concentration. These factors, therefore, do not explain the discrepancy between intact and skinned fibers during fatigue.
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PMID:Response of compressed skinned skeletal muscle fibers to conditions that simulate fatigue. 910 68

The effects of almitrine bimesylate and doxapram HCl on isometric force produced by in vitro rat diaphragm were studied during direct muscle activation at 37 degrees C. Doxapram and almitrine ameliorate respiratory failure clinically by indirectly increasing phrenic nerve activity. This study was carried out to investigate possible direct actions of these agents on the diaphragm before and after fatigue of the fibers. Two age groups of animals were chosen [6-14 wk (group 1) and 50-55 wk (group 2)] because it is known that increasing age decreases a muscle fiber's resistance to fatigue. Muscle strips were isolated from both group 1 and group 2 and directly stimulated (2-ms pulse duration, 5-15 V) to produce twitch tensions of 1.3 and 2.1 N/cm2, respectively. At low concentrations, doxapram (</=20 microg/ml) and almitrine (</=12 microg/ml) had no effect on twitch contraction or 100-Hz tetanic tension. However, 40 microg/ml doxapram and 30 microg/ml almitrine increased twitch tension by 9.0 +/- 1.4 and 11.6 +/- 1.9%, respectively, in animals of group 2 (n = 5). A fatigue protocol consisting of low-frequency stimulation (30-Hz trains, 250-ms duration every 2 s for 5 min) caused a reduction of twitch tension in animals of group 1 (48 +/- 4% of control) and group 2 (28 +/- 4% of control). At 90 min postfatigue, the twitch tension recovered to 72 +/- 3 and 42 +/- 2% of control values in group 1 and group 2, respectively. In the presence of doxapram (20 microg/ml), there was a significant increase in the recovery of twitch tension at 90 min in group 1 and group 2 (84.5 +/- 3.2 and 80.1 +/- 2.8%, respectively) compared with controls at 90 min postfatigue. In the presence of almitrine (12 microg/ml), there was a full recovery from fatigue in group 1 animals (100% of control) and a recovery to 95.6 +/- 2.1% of control in group 2 animals at 90 min. These results demonstrate a significant improvement in the rapidity and magnitude of recovery from fatigue in the rat diaphragm muscle in the presence of both doxapram and, especially, almitrine. These effects may be due to changes in intracellular calcium, ADP/ATP ratios, or oxygen free radical scavenging.
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PMID:Almitrine and doxapram decrease fatigue and increase subsequent recovery in isolated rat diaphragm. 921 44

The manifestations of fatigue, as observed by reductions in the ability to produce a given force or power, are readily apparent soon after the initiation of intense activity. Moreover, following the activity, a sustained weakness may persist for days or even weeks. The mechanisms responsible for the impairment in performance are various, given the severe strain imposed on the multiple organ systems, tissues and cells by the activity. At the level of the muscle cell, ATP utilization is dramatically accelerated in an attempt to satisfy the energy requirements of the major processes involved in excitation and contraction namely sarcolemmal Na+/K+ exchange, sarcoplasmic reticulum Ca2+ sequestration and actomyosin cycling. In an attempt to maintain ATP levels, high-energy phosphate transfer, glycolysis and oxidative phosphorylation are recruited. With intense activity, ATP production rates are unable to match ATP utilization rates, and reductions in ATP occur accompanied by accumulation of a range of metabolic by-products such as hydrogen ions, inorganic phosphate, AMP, ADP and IMP. Selective by-products are believed to disturb Na+/K+ balance, Ca2+ cycling and actomyosin interaction, resulting in fatigue. Cessation of the activity and normalization of cellular energy potential results in a rapid recovery of force. This type of fatigue is often referred to as metabolic. Repeated bouts of high-intensity activity can also result in depletion of the intracellular substrate, glycogen. Since glycogen is the fundamental fuel used to sustain both glycolysis and oxidative phosphorylation, fatigue is readily apparent as cellular resources are exhausted. Intense activity can also result in non-metabolic fatigue and weakness as a consequence of disruption in internal structures, mediated by the high force levels. This type of impairment is most conspicuous following eccentric muscle activity; it is characterized by myofibrillar disorientation and damage to the cytoskeletal framework in the absence of any metabolic disturbance. The specific mechanisms by which the high force levels promote muscle damage and the degree to which the damage can be exacerbated by the metabolic effects of the exercise remain uncertain. Given the intense nature of the activity and the need for extensive, high-frequency recruitment of muscle fibres and motor units in a range of synergistic muscles, there is limited opportunity for compensatory strategies to enable performance to be sustained. Increased fatigue resistance would appear to depend on carefully planned programmes designed to adapt the excitation and contraction processes, the cytoskeleton and the metabolic systems, not only to tolerate but also to minimize the changes in the intracellular environment that are caused by the intense activity.
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PMID:Mechanisms of muscle fatigue in intense exercise. 923 50

The effect of sustained submaximal exercise on muscle energetics has been studied on the single-fiber level in human skeletal muscle. Seven subjects cycled to fatigue (mean 77 min) at a work rate corresponding to approximately 75% of maximal O2 uptake. Biopsies were taken from the vastus lateralis muscle at rest, at fatigue, and after 5 min of recovery. Muscle glycogen decreased from 444 +/- 40 (SE) mmol glucosyl units/kg dry wt at rest to 94 +/- 16. Postexercise glycogen was inversely correlated (P < 0.01) to muscle content of inosine monophosphate, a catabolite of ATP. Phosphocreatine (PCr) in mixed-fiber muscle decreased at fatigue to 37% but was restored above the initial value (106.5%, P < 0.025) after 5 min of recovery. The overshoot was localized to type I fibers. The rapid reversal of PCr is in contrast to the slow recovery in contraction force. Pi increased at fatigue but less than that expected from the changes in PCr and other phosphate compounds. Mean PCr at rest was approximately 20% higher in type II than in type I fibers (86.4 +/- 3.6 and 71.6 +/- 1.8 mmol/kg dry wt, respectively, P < 0.05), but at fatigue similar PCr contents were observed in the two fiber types. Reduction in PCr in all fibers at fatigue suggests that all fibers were recruited at the end of exercise. PCr content in single fibers showed a great variability in samples at rest, exercise, and recovery. The variability was more pronounced than for ATP, and the data suggest that it is due to interfiber physiological-biochemical differences. At fatigue ATP was maintained relatively high in all single fibers, but a pronounced depletion of PCr was observed in a large number of fibers, and this may contribute to fatigue through the associated increases in Pi or/and free ADP. It is noteworthy that the increase in calculated free ADP at fatigue was similar to that after high-intensity exercise.
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PMID:Phosphocreatine content in single fibers of human muscle after sustained submaximal exercise. 925 54

A decline of isometric force production is one characteristic of skeletal muscle fatigue. In fatigue produced by repeated short tetani, this force decline can be divided into two components: a reduction of the cross-bridges' ability to generate force, which comes early; and a reduction of the sarcoplasmic reticulum Ca2+ release, which develops late in fatigue. Acidification due to lactic acid accumulation has been considered as an important cause of the reduced cross-bridge force production. However, in mammalian muscle it has been shown that acidification has little effect on isometric force production at physiological temperatures. By exclusion, in mammalian muscle fatigue, the reduction of force due to impaired cross-bridge function would be caused by accumulation of inorganic phosphate ions, which results from phosphocreatine breakdown. The reduction of sarcoplasmic reticulum Ca2+ release in late fatigue correlates with a decline of ATP and we speculate that the reduced Ca2+ release is caused by a local increase of the ADP/ATP ratio in the triads.
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PMID:Mechanisms underlying the reduction of isometric force in skeletal muscle fatigue. 957 70

Limitations in energy supply is a classical hypothesis of muscle fatigue. The present paper reviews the evidence available from human studies that energy deficiency is an important factor in fatigue. The maximal rate of energy expenditure determined in skinned fibres is close to the rate of adenosine triphosphate (ATP) utilisation observed in vivo and data suggest that performance during short bursts of exercise (<5 s duration) primarily is limited by other factors than energy supply (e.g. Vmax of myosine adenosine triphosphatase (ATPase), motor unit recruitment, engaged muscle mass). Within 10 s of exercise maximal power output decreases considerably and coincides with depletion of phosphocreatine. During recovery, maximal force and power output is restored with a similar time course as the resynthesis of phosphocreatine. Increases in muscle store of phosphocreatine through dietary supplementation with creatine increases performance during high-intensity exercise. These findings support the hypothesis that energy supply limits performance during high-intensity exercise. It is well documented that pre-exercise muscle glycogen content is related to performance during moderate intensity exercise. Recent data indicates that the interfibre variation in phosphocreatine is large after prolonged exercise to fatigue and that some fibres are depleted to the same extent as after high-intensity exercise. Despite relatively small decreases in ATP, the products of ATP hydrolysis (Pi and free ADP) may increase considerably. Free ADP calculated from the creatine kinase reaction increases 10-fold both after high-intensity exercise and after prolonged exercise to fatigue. It is suggested that local increases in ADP may reach inhibitory levels for the contraction process.
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PMID:Energy supply and muscle fatigue in humans. 957 71

1. The mechanism behind the reduction in shortening velocity in skeletal muscle fatigue is unclear. In the present study we have measured the maximum shortening velocity (V0) with slack tests during fatigue produced by repeated, 350 ms tetani in intact, single muscle fibres from the mouse. We have focused on two possible mechanisms behind the reduction in V0: reduced tetanic Ca2+ and accumulation of ADP. 2. During fatigue V0 initially declined slowly, reaching 90 % of the control after about forty tetani. The rate of decline then increased and V0 fell to 70 % of the control in an additional twenty tetani. The reduction in isometric force followed a similar pattern. 3. Exposing unfatigued fibres to 10 microM dantrolene, which reduces tetanic Ca2+, lowered force by about 35 % but had no effect on V0. 4. In order to see if ADP might increase rapidly during ongoing contractions, we used a protocol with a tetanus of longer duration bracketed by standard-duration tetani. V0 in these three tetani were not significantly different in control, whereas V0 was markedly lower in the longer tetanus during fatigue and in unfatigued fibres where the creatine kinase reaction was inhibited by 10 microM dinitrofluorobenzene. 5. We conclude that the reduction in V0 during fatigue is mainly due to a transient accumulation of ADP, which develops during contractions in fibres with impaired phosphocreatine energy buffering.
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PMID:Mechanisms underlying reduced maximum shortening velocity during fatigue of intact, single fibres of mouse muscle. 962 83

Earlier work on Notothenioids led to the hypothesis that a reduced glycolytic capacity is a general adaptation to low temperatures in Antarctic fish. In our study this hypothesis was reinvestigated by comparing changes in the metabolic status of the white musculature in two related zoarcid species, the stenothermal Antarctic eelpout Pachycara brachycephalum and the eurythermal Zoarces viviparus during exercise and subsequent recovery at 0 degreesC. In both species, strenuous exercise caused a similar increase in white muscle lactate, a drop in intracellular pH (pHi) by about 0.5 pH units, and a 90% depletion of phosphocreatine. This is the first study on Antarctic fish that shows an increase in white muscle lactate concentrations. Thus the hypothesis that a reduced importance of the glycolytic pathway is characteristic for cold-adapted polar fish cannot hold. The recovery process, especially the clearance of white muscle lactate, is significantly faster in the Antarctic than in temperate eelpout. Based on metabolite data, we calculated that during the first hour of recovery aerobic metabolism is increased 6.6-fold compared with resting rates in P. brachycephalum vs. an only 2.9-fold increase in Z. viviparus. This strong stimulation of aerobic metabolism despite low temperatures may be caused by a pronounced increase of free ADP levels, in the context of higher levels of pHi and ATP, which is observed in the Antarctic species. Although basal metabolic rates are identical in both species, the comparison of metabolic rates during situations of high-energy turnover reveals that the stenothermal P. brachycephalum shows a higher degree of metabolic cold compensation than the eurythermal Z. viviparus. Muscular fatigue after escape swimming may be caused by a drop of the free energy change of ATP hydrolysis, which is shown to fall below critical levels for cellular ATPases in exhausted animals of both species.
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PMID:High-energy turnover at low temperatures: recovery from exhaustive exercise in Antarctic and temperate eelpouts. 984 52

To examine the effect of ambient temperature on metabolism during fatiguing submaximal exercise, eight men cycled to exhaustion at a workload requiring 70% peak pulmonary oxygen uptake on three separate occasions, at least 1 wk apart. These trials were conducted in ambient temperatures of 3 degrees C (CT), 20 degrees C (NT), and 40 degrees C (HT). Although no differences in muscle or rectal temperature were observed before exercise, both muscle and rectal temperature were higher (P < 0.05) at fatigue in HT compared with CT and NT. Exercise time was longer in CT compared with NT, which, in turn, was longer compared with HT (85 +/- 8 vs. 60 +/- 11 vs. 30 +/- 3 min, respectively; P < 0.05). Plasma epinephrine concentration was not different at rest or at the point of fatigue when the three trials were compared, but concentrations of this hormone were higher (P < 0.05) when HT was compared with NT, which in turn was higher (P < 0.05) compared with CT after 20 min of exercise. Muscle glycogen concentration was not different at rest when the three trials were compared but was higher at fatigue in HT compared with NT and CT, which were not different (299 +/- 33 vs. 153 +/- 27 and 116 +/- 28 mmol/kg dry wt, respectively; P < 0.01). Intramuscular lactate concentration was not different at rest when the three trials were compared but was higher (P < 0.05) at fatigue in HT compared with CT. No differences in the concentration of the total intramuscular adenine nucleotide pool (ATP + ADP + AMP), phosphocreatine, or creatine were observed before or after exercise when the trials were compared. Although intramuscular IMP concentrations were not statistically different before or after exercise when the three trials were compared, there was an exercise-induced increase (P < 0.01) in IMP. These results demonstrate that fatigue during prolonged exercise in hot conditions is not related to carbohydrate availability. Furthermore, the increased endurance in CT compared with NT is probably due to a reduced glycogenolytic rate.
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PMID:Effect of ambient temperature on human skeletal muscle metabolism during fatiguing submaximal exercise. 1006 3


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