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

Rats were acutely administered ethanol as a primed constant infusion in order to produce sustained blood ethanol levels of 8-12 or 55-65 mM. At the end of ethanol infusion the livers were either freeze-clamped in vivo or isolated and perfused for metabolic studies. The rate of gluconeogenesis and its responsiveness to phenylephrine (10 microM), prostaglandin F2 alpha (5 microM) and glucagon (10 nM), as well as the redox state of the cytosolic NAD(+)-NADH system were assessed in livers isolated from acutely ethanol-treated rats, and subsequently perfused without ethanol. For liver clamped in vivo, high- but not low-ethanol treatment decreased the ATP content by 31% and slightly increased ADP and AMP content, resulting in a decreased energy charge (11%). Glutamate and aspartate content was also increased in high-dose ethanol-infused rats with no changes in malate and 2-oxoglutarate content. Gluconeogenesis with saturating concentrations of lactate (4 mM)+pyruvate (0.4 mM) was delayed in reaching a plateau in the livers of high-dose ethanol-treated rats and its response to all three stimulators was impaired. Low-dose ethanol treatment only decreased the liver response to phenylephrine. While the perfused livers of low-dose ethanol-treated rats displayed no changes in adenine nucleotide content, the livers of high-dose ethanol-treated rats had a decreased ATP (35%) and an increased AMP (77%) content, paralleled by a fall in the total adenine nucleotides (14%) and energy charge (14%). No differences were observed between the saline- and ethanol-treated rats with respect to malate-aspartate shuttle intermediate concentration in perfused livers. Also, the livers of high-, but not low-dose ethanol-treated rats had a more negative value of NAD(+)-NADH redox state as compared to the livers of control rats. The data suggest that acute ethanol intoxication produces changes in liver metabolism and its responsiveness to hormones/agonists that are demonstrable for at least 2 hr after isolation and perfusion of the liver.
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PMID:Effects of acute alcohol intoxication on gluconeogenesis and its hormonal responsiveness in isolated, perfused rat liver. 135 76

There are at least 5 metabolic causes of fatigue, a decrease in the phosphocreatine level in muscle, proton accumulation in muscle, depletion of the glycogen store in muscle, hypoglycaemia and an increase in the plasma concentration ratio of free tryptophan/branched-chain amino acids. Proton accumulation may be a common cause of fatigue in most forms of exercise and may be an important factor in fatigue in those persons who are chronically physically inactive and also in the elderly: thus, the aerobic capacity markedly decreases under these conditions, so that ATP must be synthesized by the much less efficient anaerobic system. A marked increase in the plasma fatty acid level, which may occur when liver glycogen store is depleted and when hypoglycaemia results, or during intermittent exercise when the rate of fatty acid oxidation may not match the mobilisation of fatty acids, could be involved indirectly in fatigue. This is because such an increase in the plasma level of fatty acids raises the free plasma concentration of tryptophan, which can increase the entry of tryptophan into the brain, which will increase the brain level of 5-hydroxytryptamine: there is evidence that the latter may be involved in central fatigue. In this case, provision of branched-chain amino acids in order to maintain the resting plasma concentration ratio of free tryptophan/branched-chain amino acids should delay fatigue--there is prima facie evidence in support of this hypothesis. This hypothesis may have considerable clinical importance.
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PMID:Physical and mental fatigue: metabolic mechanisms and importance of plasma amino acids. 136 Mar 9

The purpose of this study was to determine the concentration of ATP, phosphocreatine (PC), Pi, lactate, and glycogen in single frog skeletal muscle fibers and assess their role in the etiology of muscle fatigue. The frog semitendinosus (ST) muscle was fatigued, quick frozen at selected time points of recovery, and freeze-dried, and single fibers were dissected, weighed, and assayed for ATP, PC, lactate, Pi, and glycogen. The fatigue protocol reduced peak tetanic force (Po) to 8.5% of initial, while ATP and PC decreased from 45.18 to 33.16 and 128.90 to 28.76 mmol/kg dry wt, respectively. Lactate and Pi increased from 29.36 to 100.84 and 33.04 to 142.50 mmol/kg dry wt, respectively. It is doubtful that the small decline in ATP limited cross-bridge force production. Although a significant correlation between the recovery of PC and Po was demonstrated (r = 0.994), the time period showing the fastest rate of force recovery coincided with little change in PC. A significant correlation was demonstrated between the recovery of both total and the H2PO4- form of Pi and Po. In conclusion, the results of this study are incompatible with the hypothesis that the high-energy phosphates (ATP and PC) mediate muscle fatigue. The large increase in Pi with stimulation and the high correlation between the recovery of both total and the H2PO4- form of Pi and Po support a role for Pi in the production of skeletal muscle fatigue.
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PMID:Muscle fatigue in the frog semitendinosus: role of the high-energy phosphates and Pi. 141 69

Intracellular free Mg2+ concentration ([Mg2+]i) was measured in isolated single fibres of Xenopus muscle using the fluorescent Mg2+ indicator furaptra. In resting muscle the [Mg2+]i was 1.7 mM in a Mg(2+)-free Ringer solution. There was no significant change in [Mg2+]i over 2 h in Mg(2+)-free Ringer solution. Elevating extracellular [Mg2+] to 40 mM for 5 min caused a small rise (0.13 mM) in [Mg2+]i. There was no detectable rise in [Mg2+]i after 5 min in Na(+)-free Ringer solution. These results suggest that the membrane is relatively impermeable to Mg2+ and that there was no detectable Na(+)-Mg2+ exchange over 5 min. When muscle fibres were fatigued by repeated tetani continued until force declined to about 40% of control, [Mg2+]i showed characteristic changes. During the early period of fatigue when force first showed a small decline and then became almost stable, [Mg2+]i was unchanged; during the final period of fatigue when force declined more rapidly, [Mg2+]i increased by 0.8 mM. Recovery of [Mg2+]i took about 30 min. Recovery of force was complex: tetanic force first declined (post-contractile depression) and then slowly recovered to control. Since the minimum force occurred at about the time when [Mg2+]i had recovered, it seems unlikely that post-contractile depression is caused by elevated [Mg2+]i. Rigor, produced by inhibiting oxidative phosphorylation and glycolysis, was associated with a larger increase (1.6 mM) in [Mg2+]i than fatigue. The rise in [Mg2+]i during fatigue and metabolic blockade could be explained as release of Mg2+ normally bound to ATP. A model of the metabolic changes and the resulting increase in [Mg2+]i explains our results reasonably well.
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PMID:Myoplasmic Mg2+ concentration in Xenopus muscle fibres at rest, during fatigue and during metabolic blockade. 141 55

All exercise draws first on intramuscular stores of ATP and creatine phosphate; initially these are replenished by anaerobic glycolysis. The lactic acid produced contributes to the rapid development of fatigue in high intensity exercise. Aerobic metabolism (at first mainly of glycogen, later increasingly of fat) is the principal route of ATP resynthesis in activities lasting longer than 2 min, but can only maintain work-rates about 1/4 of those possible in very brief bursts. Blood lactate rises at the higher aerobic work rates. 'Lactate threshold' (LT: approximately 2 mmol/l) is almost exactly the speed at which endurance races are won, and close to those apparently providing optimal aerobic training. This training, predominantly of muscle aerobic capacity, elevates LT more than maximum oxygen consumption. LT is not now thought to indicate oxygen-deprivation, but intracellular adjustments driving oxidative phosphorylation faster. Ventilatory breakpoints, formerly considered to indicate LT, correlate more closely with the accumulation of potassium than lactate.
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PMID:Aerobic exercise, anaerobic exercise and the lactate threshold. 145 Aug 85

1. The role of the myoplasmic free Mg2+ concentration ([Mg2+]i) in fatigue was studied in intact single fibres isolated from mouse skeletal muscle. Fatigue was produced by repeated tetanic stimulation. The fluorescent Mg2+ indicator furaptra was pressure injected into fibres. In vivo calibrations were performed to convert fluorescence signals into [Mg2+]i. 2. [Mg2+]i at rest was 0.78 +/- 0.05 mM (mean +/- S.E.M., n = 14). An increase of the extracellular [Mg2+] from 0.5 to 20 mM resulted in a small elevation of [Mg2+]i (86 microM in 5 min). Removal of extracellular Na+ did not affect [Mg2+]i. An intracellular alkanization of about 0.6 pH units gave a [Mg2+]i reduction of 65 microM. 3. During fatiguing stimulation [Mg2+]i initially remained almost constant and it then suddenly started to rise towards the end of the stimulation period. The onset of the [Mg2+]i rise was always followed by a rapid tension decline. In fatigue [Mg2+]i was approximately twice as high as at rest. 4. Fibres were injected with MgCl2 to study if the rise in [Mg2+]i could explain the tension decline in fatigue. An elevation of [Mg2+]i was accompanied by a tension reduction but the [Mg2+]i for a given tension was generally much higher in rested fibres injected with MgCl2 than in fatigued fibres. Thus the rise in [Mg2+]i as such cannot explain the tension reduction in fatigue. 5. Injection of MgCl2 was also used to assess the intracellular Mg2+ buffering. The mean Mg2+ buffer power (i.e. the ratio of the change in [Mg2+]i to the amount of Mg2+ added) was 0.62. 6. ATP is the quantitatively most important binding site for Mg2+ at rest and ATP breakdown is then a likely source of the [Mg2+]i increase in fatigue. The role of ATP breakdown in the increase of [Mg2+]i was studied with metabolic inhibition: fibres were exposed to iodoacetic acid to inhibit glycolysis and cyanide to inhibit oxidative phosphorylation. The pattern during metabolic inhibition was similar to that observed during fatigue. After remaining almost constant during a lengthy period, [Mg2+]i rose rapidly and this rise preceded a period of rapid tension decline. The fibres thereafter went into rigor and [Mg2+]i stabilized at an elevated level; the mean [Mg2+]i increase in rigor was 1.30 mM. 7. We have used modelling to determine the likely change in the intracellular ATP concentration ([ATP]i) for the observed changes in [Mg2+]i.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Myoplasmic free Mg2+ concentration during repetitive stimulation of single fibres from mouse skeletal muscle. 146 36

It has long been appreciated that rates of ATP utilization and production need to be extremely closely balanced. To put it in molecular rather than molar terms, in human muscle engaged in a 15-min work protocol, approximately 3.3 x 10(20) ATP/g are used and resynthesized at approximately 100 times the resting cycling rates before fatigue, during which time only a 20-25% decrease in the ATP pool is sustained. Analysis of how such remarkable regulatory precision is achieved suggests that in resting muscle myosin behaves as a latent catalyst whose full catalytic potential 1) is realized with the arrival of an activator signal (Ca2+) and 2) is tempered with reaction products; such proactive control, initiated at ATP utilization, sets the required flux through ATP-producing pathways. For any given enzyme step in ATP-producing pathways, reaction velocity (v) becomes the independent parameter, with substrate concentration ([S], the dependent parameter) being adjusted accordingly. Because the dynamic range for muscles (change from resting to maximum ATP turnover rates) can exceed 100-fold, in many studies of working muscle the percent change in ATP turnover rate exceeds (sometimes by very large margins) the percent change in [S]. These observations are not easily explained by current metabolic regulation models but are consistent with pathway enzymes behaving as latent catalysts in resting muscle. In this view, the unmasking of such latent catalytic potential is the main explanation for how large changes in v can be achieved with modest (sometimes immeasurable) changes in [S].(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulating ATP turnover rates over broad dynamic work ranges in skeletal muscles. 828 52

The combined effects of inspiratory resistive loaded breathing (IRL) and hypoxemia on transdiaphragmatic pressure (Pdi) in nine 1-mo-old Yorkshire piglets were studied. IRL was adjusted to increase spontaneously generated Pdi five to six times above baseline but maintain arterial PCO2 < 70 Torr to prevent hypercapnic depression of diaphragmatic contractility. Measurements of ventilation, blood gases and pH, Pdi, diaphragmatic electromyogram, Pdi during phrenic nerve stimulation, diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 2 h of IRL, and then after 1 h of hypoxemia (arterial PO2 approximately 40 Torr) combined with IRL. Diaphragmatic muscle samples were obtained after study completion and immediately frozen in liquid nitrogen for determination of tissue ATP, phosphocreatine, lactate, and glycogen levels. Ten 1-mo-old piglets were subjected to IRL alone and served as controls. IRL alone resulted in significant impairment of Pdi generation. The addition of hypoxemia for 1 h did not further compromise Pdi in comparison to control animals who were subjected to IRL alone. Blood flow to both the costal and crural segments of the diaphragm increased significantly during IRL; the addition of the hypoxemic stress resulted in further significant augmentation of blood flow to both segments of the diaphragm. No differences were noted in diaphragmatic muscle tissue ATP, phosphocreatine, or glycogen between control and IRL animals or between control and IRL plus hypoxemia animals. Muscle lactate levels increased significantly in the IRL plus hypoxemia animals only. The data from this study suggest that moderate hypoxemia during resistive-loaded breathing in the piglet does not accentuate diaphragmatic fatigue.
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PMID:Effect of inspiratory resistive loaded breathing and hypoxemia on diaphragmatic function in the piglet. 147 65

Recent investigations from our and other laboratories indicate that glycogen is a carbon-chain precursor in muscle for the synthesis of TCA cycle intermediates and glutamine. During intense exercise and in conditions of a relative lack of energy (hypoxia, trauma, sepsis) the metabolism of branched-chain amino acids (BCAA) is accelerated in muscle. In the primary BCAA aminotransferase reaction 2-oxoglutarate is used as amino-group acceptor (putting a carbon-drain on the TCA cycle) under formation of glutamate. Glutamate will subsequently react with ammonia, generated in the AMP deaminase reaction or by deamination of amino acids, under formation of glutamine in a reaction catalysed by glutamine synthetase (glutamate + ammonia + ATP--> glutamine + ADP). Muscle glycogen stores may be smaller or less available at high altitude. It is hypothesized that this will lead to premature fatigue (due to both a lack of fuel and of TCA cycle carbon-precursor) and to a reduction in the synthesis rate of glutamine. A chronic reduction in the synthesis rate of glutamine during a long term stay at high altitude on its turn may lead to gut atrophy, bacterial translocation, endotoxemia, muscle protein catabolism and a weakened immune status.
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PMID:Amino acid metabolism, muscular fatigue and muscle wasting. Speculations on adaptations at high altitude. 148 45

Muscle contractions at lengths below the optimum for force development were previously found to cause less fatigue than contractions at the optimum length (Lo). Decreased fatigability was suggested to arise from fewer cross-bridge interactions in shortened sarcomeres. In the present study, this suggestion was tested by monitoring energy use of human ankle dorsiflexor muscles during and after contractions at Lo and shortened lengths (Ls) with phosphorus nuclear magnetic resonance spectroscopy. The nuclear magnetic resonance spectra indicated similar rates of ATP use during contractions at Lo and Ls. Phosphocreatine, at an initial concentration of 37 mM, was reduced to an equivalent extent by 2 min of ischemic exercise at Lo (to 2.3 mM) and Ls (to 4.7 mM). Changes in pH (indicating glycolytic ATP production) were also equivalent at Lo and Ls. Exercise caused pH to fall from an initial level of 7.07 to 6.5 at Lo and to 6.53 at Ls. In relation to previous experiments performed under similar conditions on human ankle dorsiflexor muscles, the present experiments suggest that in shortened muscle the decreased force found in this and previous studies and the decreased fatigability that was previously found may not be simply due to fewer cross-bridge interactions in shortened sarcomeres. Examination of the relationships between developed force and levels of metabolites suggests that changes of force during fatigue and recovery correlate better with intracellular [Pi] and H2PO4- than with [H+].
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PMID:Influence of human muscle length on energy transduction studied by 31P-NMR. 150 63


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