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

Within working muscle, development of conditions that directly influence exercise performance is dependent on many factors, including: intensity and duration of exercise, type of skeletal muscle fibres recruited, cardiovascular support to the working fibres and the inherent metabolic characteristics of the contracting fibres. In general, it is possible to identify factors that seem to alter exercise performance only at relatively intense exercise conditions. During prolonged moderately intense exercise (e.g. 70-80% maximal oxygen consumption for at least 60-90 min) decline in performance is related to the depletion of glycogen within the working muscle. Although the cause of muscle performance decline during very intense exercise is not known, an extreme acidosis is found, especially in fast-twitch muscle, which could significantly disrupt normal metabolic and contractile processes. During fatigue caused by intense contraction conditions, ATP content decreases (by approx. 50%) and there is a stoichiometric production of IMP and ammonia in fast-twitch muscle. This loss in adenine nucleotide content is dependent on the severity of the contraction conditions relative to the functional aerobic capacity of the muscle fibre, since fast-twitch red (high mitochondria, high blood flow) and fast-twitch white (low mitochondria, low blood flow) muscles respond differently. In contrast, during similarly intense contraction conditions, rat slow-twitch muscle fibres maintain their ATP content and do not produce significant amounts of IMP. Indirect evidence suggests that a similar contrast between fibres occurs in humans during maximal exercise. Thus, there seems to be a fundamental difference between fast- and slow-twitch muscles in the management of their adenine nucleotide contents during intense contraction conditions. Whether this is related to the known differences in the fatigue process between these fibre types is not known.
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PMID:Metabolic and circulatory limitations to muscular performance at the organ level. 403 72

This report describes changes of the rate of ATP hydrolysis in single, intact muscle fibres during the development of fatigue induced by intermittent tetanic stimulation. High (type 3) and low (type 1) oxidative muscle fibres dissected from the iliofibularis muscle of Xenopus laevis were studied at 20 degrees C. The rate of ATP hydrolysis was calculated during different time intervals from changes in the content of nucleotides, creatine compounds and lactate, as well as lactate efflux and oxygen uptake. During the first phase of intermittent stimulation, phosphocreatine is fully reduced while the rate of oxygen consumption increases to its maximum, the lactate content increases to a maximum level, and a small amount of IMP is formed; the rate of ATP hydrolysis in type 3 fibres is constant while force decreases, whereas the rate decreases approximately in proportion to force in type 1 fibres. After the first phase, the rate of ATP hydrolysis in type 3 fibres decreases slightly and the fibres reach a steady metabolic state in which the rates of ATP formation and hydrolysis are equal; in type 1 fibres a drastic change of the rate of ATP hydrolysis occurs and a steady metabolic state is not reached. On the basis of the time courses of the metabolic changes, it is concluded that the rate of ATP hydrolysis in type 3 fibres is reduced by acidification and/or a reduced calcium efflux from the sarcoplasmic reticulum, whereas in type 1 fibres inorganic phosphate and/or acidification inhibit the rate initially and ADP is a likely candidate to explain the drastic fall of the rate of ATP hydrolysis during late phases of fatiguing stimulation.
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PMID:ATP formation and ATP hydrolysis during fatiguing, intermittent stimulation of different types of single muscle fibres from Xenopus laevis. 812 21

The role of prolonged electrical stimulation on sarcoplasmic reticulum (SR) Ca2+ sequestration measured in vitro and muscle energy status in fast white and red skeletal muscle was investigated. Fatigue was induced by 90 min intermittent 10-Hz stimulation of rat gastrocnemius muscle, which led to reductions (p < 0.05) in ATP, creatine phosphate, and glycogen of 16, 55, and 49%, respectively, compared with non-stimulated muscle. Stimulation also resulted in increases (p < 0.05) in muscle lactate, creatine, Pi, total ADP, total AMP, IMP, and inosine. Calculated free ADP (ADPf) and free AMP (AMPf) were elevated 3- and 15-fold, respectively. No differences were found in the metabolic response between tissues obtained from the white (WG) and red (RG) regions of the gastrocnemius. No significant reductions is SR Ca2+ ATPase activity were observed in homogenate (HOM) or a crude SR fraction (CM) from WG or RG muscle following exercise. Maximum Ca2+ uptake in HOM and CM preparations was similar in control (C) and stimulated (St) muscles. However, Ca2+ uptake at 400 nM free Ca2+ was significantly reduced in CM from RG (0.108 +/- 0.04 to 0.076 +/- 0.02 mumol.mg-1 protein.min-1 in RG - C and RG - St, respectively). Collectively, these data suggest that reductions in muscle energy status are dissociated from changes in SR Ca2+ ATPase activity in vitro but are related to Ca2+ uptake at physiological free [Ca2+ bd in fractionated SR from highly oxidative muscle. Dissociation of SR Ca2+ ATPase activity from Ca2+ uptake may reflect differences in the mechanisms evaluated by these techniques.
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PMID:Effects of prolonged low frequency stimulation on skeletal muscle sarcoplasmic reticulum. 856 84

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 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

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

To examine the effect of training status on muscle metabolism during exercise, seven endurance-trained [peak oxygen uptake (VO(2 peak)) = 65.8 +/- 2.4 ml. kg(-1). min(-1)] and six untrained (VO(2 peak) = 46. 2 +/- 1.9 ml. kg(-1). min(-1)) men cycled to fatigue at a work rate calculated to require 70% VO(2 peak). Time to exhaustion was 36% longer (P < 0.01) in trained (TR) compared with untrained (UT) men (148 +/- 11 vs. 95 +/- 8 min). Although intramuscular glycogen content was reduced (P < 0.05) in both TR and UT at fatigue, IMP, a marker of a mismatch between ATP supply and demand, was only elevated (P < 0.01) in UT muscle at fatigue and was approximately fourfold higher at this point in UT compared with TR. These data demonstrate that fatiguing submaximal exercise was associated with a similar low level of intramuscular glycogen in both TR and UT men, but a mismatch between ATP supply and demand only occurred in UT individuals.
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PMID:Muscle IMP accumulation during fatiguing submaximal exercise in endurance trained and untrained men. 1040 85

In normal skeletal muscle, prolonged stimulation results in some cellular adenosine triphosphate (ATP) being converted to adenosine monophosphate (AMP) and then deaminated to inosine monophosphate (IMP). Here, we investigate whether the build-up of IMP contributes to muscle fatigue and also determine what happens if AMP is instead hydrolyzed to adenosine. Rat skeletal muscle fibers were mechanically skinned, allowing rapid manipulation of the cytoplasmic conditions, while still retaining the normal excitation-contraction coupling mechanism. Inosine monophosphate (3 mM) had no noticeable effect on either depolarization-induced or caffeine-induced Ca(2+) release from the sarcoplasmic reticulum. In contrast, 3 mM adenosine substantially inhibited depolarization-induced force responses and completely abolished caffeine activation of Ca(2+) release in a reversible fashion, with noticeable inhibition occurring even at 0.4 mM adenosine. These results indicate that IMP does not appreciably inhibit excitation-contraction coupling in normal muscle, and further suggest that the build up of adenosine may be at least partly responsible for the early onset of fatigue occurring in subjects with myoadenylate deaminase deficiency.
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PMID:Adenosine inhibits depolarization-induced Ca(2+) release in mammalian skeletal muscle. 1056 80

The aim was to study metabolic response and locomotion pattern in Standardbred trotters during incremental treadmill exercise performed by increasing speed by 1 m/s in 1 min steps (start 7 m/s) until the onset of fatigue. The test protocol included determination of oxygen uptake, heart rate (HR), stride length (SL) and stride frequency (SF). Venous blood samples were collected at rest, at the end of each exercise step and after 30 min of recovery. Muscle biopsies were taken at rest and post exercise and muscle temperature was measured after exercise. As horses fatigued at different speed steps (9-11 m/s), variation was seen in running time (180-300 s), oxygen uptake (109-170 ml/kg bwt min), HR (200-225 beats/min), SL (4.4-5.7 m) and SF (116-130 strides/min) at the last speed step. Increased mean plasma lactate concentration (20.5 mmol/l) was seen at onset of fatigue and increased mean uric acid concentration after 30 min of recovery (112.8 mumol/l). After exercise, a decrease was seen in muscle ATP (7.1 mmol/kg d.w.), creatine phosphate (43.9 mmol/kg d.w.) and glycogen (160 mmol/kg d.w.), and an increase was seen in ADP (0.3 mmol/kg d.w.), AMP (0.18 mmol/kg d.w.), IMP (5.8 mmol/kg d.w.) and lactate (100.8 mmol/kg d.w.). At onset of fatigue, muscle temperature varied from 39.9-41.4 degrees C. Running time correlated with SL (r = 0.86), with an increase in IMP (r = 0.79) and AMP (r = 0.70) post exercise and with plasma uric acid concentration (r = 0.74) at 30 min of recovery. SF correlated negatively with the increase in ADP after exercise (r = 0.85). The results of this study indicate that running time during incremental treadmill exercise until the onset of fatigue is related to locomotion pattern and to a marked degree of anaerobic metabolism, especially adenine nucleotide degradation.
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PMID:Incremental treadmill exercise until onset of fatigue and its relationship to metabolic response and locomotion pattern. 1065 79

The effects of sprint training on muscle metabolism and ion regulation during intense exercise remain controversial. We employed a rigorous methodological approach, contrasting these responses during exercise to exhaustion and during identical work before and after training. Seven untrained men undertook 7 wk of sprint training. Subjects cycled to exhaustion at 130% pretraining peak oxygen uptake before (PreExh) and after training (PostExh), as well as performing another posttraining test identical to PreExh (PostMatch). Biopsies were taken at rest and immediately postexercise. After training in PostMatch, muscle and plasma lactate (Lac(-)) and H(+) concentrations, anaerobic ATP production rate, glycogen and ATP degradation, IMP accumulation, and peak plasma K(+) and norepinephrine concentrations were reduced (P<0.05). In PostExh, time to exhaustion was 21% greater than PreExh (P<0.001); however, muscle Lac(-) accumulation was unchanged; muscle H(+) concentration, ATP degradation, IMP accumulation, and anaerobic ATP production rate were reduced; and plasma Lac(-), norepinephrine, and H(+) concentrations were higher (P<0.05). Sprint training resulted in reduced anaerobic ATP generation during intense exercise, suggesting that aerobic metabolism was enhanced, which may allow increased time to fatigue.
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PMID:Skeletal muscle metabolic and ionic adaptations during intense exercise following sprint training in humans. 1105 28


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