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

Metabolic fatigue is a characteristic muscle response to intense exercise that has outstripped the rate of ATP replacement. The accumulation of metabolic by-products, namely hydrogen ions and diprotonated phosphate, interferes with actin-myosin interaction, effectively preserving muscle ATP levels by preventing further ATP hydrolysis. Muscle force and metabolite concentrations return to normal in about 5 minutes. Less intense exercise causes a more subtle, non-metabolic fatigue due to a still-undefined disturbance of excitation-contraction coupling, which can last for several hours. In this type of fatigue, greater effort is required to generate submaximal forces. Endurance exercise is mainly limited by the size of muscle glycogen stores and how efficiently they are used. Endurance training permits an athlete to work aerobically at high rates, consuming a mixture of lipid and carbohydrate fuels. When muscle glycogen is used up, exercise can only continue at the relatively low rate supportable by lipid metabolism. Anaerobic exercise is also limited by subjective factors such as dyspnoea and muscle pain, which have objective determinants. Extremely prolonged exercise can lead to general collapse because of dehydration, hyperthermia, or hypoglycaemia. None of these factors explains the phenomenon of asthenia, a subjective sense of exhaustion that produces no objective impairment of physical performance. The metabolic myopathies are experiments of nature that promise to shed new light on the biochemical basis of muscle fatigue. This will require quantitative studies of the kind provided by topical magnetic resonance spectroscopy, correlating physiology and metabolism in vivo.
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PMID:Muscle metabolism during fatigue and work. 226 24

The high cycle fatigue strength of porous coated Ti-6A1-4V is approximately 75% less than the fatigue strength of uncoated Ti-6A1-4V. This study separates the effects of three parameters thought to be responsible for this reduction: interfacial geometry, microstructure, and surface alterations brought about by sintering. To achieve the goal of one parameter variations, hydrogen-alloying treatments, which refined the lamellar microstructure of beta-annealed and porous coated Ti-6A1-4V, were formulated. The fatigue strength of smooth-surfaced Ti-6A1-4V subjected to hydrogen-alloying treatments is 643-669 MPa, significantly greater than the fatigue strength of beta-annealed Ti-6A1-4V (497 MPa) and also greater than the fatigue strength of pre-annealed, equiaxed Ti-6A1-4V (590 MPa). The fatigue strength of porous coated Ti-6A1-4V, however, is independent of microstructure. This leads to the conclusion that the notch effect of the surface porosity does not allow the material to take advantage of the superior fatigue crack initiation resistance of a refined alpha-grain size. Thus, sinternecks acts as initiated microcracks and fatigue of porous coated Ti-6A1-4V is propagation controlled.
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PMID:A parametric study of the factors affecting the fatigue strength of porous coated Ti-6A1-4V implant alloy. 227 82

This study assessed biologic response modification at three different dose levels (0.15, 1.5, and 15 mg/m2) of interferon-gamma (IFN-gamma) administered by intravenous bolus three times weekly. A final total of 24 patients were evaluable. Dose-limiting toxicity occurred at the highest dose level (15 mg/m2) and included fatigue, leukopenia, and hepatotoxicity. Evaluation of biologic response modification included assessment of 2',5'-oligoadenylate (2-5A) synthetase activity in peripheral mononuclear cells, measurement of serum beta 2-microglobulin and expression of beta 2-microglobulin on monocytes, measurement of monocyte HLA Class II expression (HLA-DR, HLA-DQ), and measurement of hydrogen peroxide generation by monocytes 24 h after the first and fourth IFN-gamma treatments. Significant increases (p less than 0.05) from baseline were seen at 24 h with all parameters except H2O2 generation. Except for enhancement of HLA-DR, even the lowest dose (0.15 mg/m2) augmented synthesis of 2-5A synthetase and HLA proteins. A dose-response effect was noted for changes in serum and monocyte beta 2-microglobulin levels but not for 2-5A synthetase levels or HLA Class II antigen expression on monocytes. After 4 doses administered over 9 days, most parameters remained increased when compared to pretreatment, but were not further enhanced when compared with levels attained after the first dose. The results of this study document the efficacy of IFN-gamma for biological activation over a wide dose range and are consistent with the postulate that immunoregulatory effects of biological therapeutics can be obtained in man at doses substantially less than those that are maximally tolerated. Further documentation of biologic response parameters by IFN-gamma at low doses will be necessary to determine the importance of biologic activation in relation to antitumor activity.
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PMID:Induced proteins in human peripheral mononuclear cells over a range of clinically tolerable doses of interferon-gamma. 250 86

1. The relationship between intracellular metabolites and the generation of force during fatigue has been examined in the first dorsal interosseous muscle of the hand. With the arm made ischaemic, the muscle was fatigued by three bouts of maximal voluntary contraction, leaving approximately three minutes ischaemic rest between contractions. During one series of experiments intracellular phosphorus metabolites were measured by nuclear magnetic resonance during the intervals between the fatiguing contractions: in the second series contractile properties were tested with brief electrical stimulation during the rest intervals. 2. The relationships between loss of force and change in metabolite concentrations obtained with four normal subjects were compared with those from one subject with myophosphorylase deficiency (MPD) who could not utilize muscle glycogen and therefore produced no hydrogen ion from glycolysis during exercise. 3. For both the MPD and normal subjects the relationship between relative force loss and inorganic phosphate (Pi) concentration was curvilinear, force changing little in the early stages of the contraction when the intracellular Pi was accumulating rapidly but falling faster when the Pi was above 25 mM and increasing relatively slowly. 4. In the normal subjects intracellular pH fell from a mean of 7.03 +/- 0.01 (mean +/- S.E. of mean, n = 19) in the fresh muscle to 6.51 +/- 0.02 at the end of the fatiguing exercise; force, as a percentage of the initial value, fell in proportion to the increase in H+ concentration. In the MPD subject pH did not change and force loss was therefore independent of H+ accumulation. In the normal subjects the force of the fatiguing muscle showed an approximately linear relationship with the concentration of the monobasic form of inorganic phosphate. However, the MPD subject showed a quite different relationship, with force loss being much greater for a given concentration of monobasic phosphate. This result indicates that monobasic phosphate is not a unique determinant of force loss in fatigued muscle. 5. During the first 60 s of recovery in the normal subjects, pH remained low while force recovered, indicating a mechanism of force loss that was independent of H+ accumulation. However, the recovery of force was not complete, so that for comparable phosphocreatine contents the recovering, more acid, muscle generated less force than the muscle that was being fatigued. It was estimated that H(+)-dependent and independent mechanisms contributed roughly equally to the observed force loss. The relationship between force and the concentration of monobasic phosphate differed in fatiguing and recovering muscle.
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PMID:Changes in force and intracellular metabolites during fatigue of human skeletal muscle. 262 21

Muscular fatigue is of critical importance to performance and as such has been the subject of numerous investigations. However, a clear cause remains elusive. Although many factors have been identified, this review deals only with those which occur distal to the neuromuscular junction. Factors discussed include: energy supply (ATP/creatine phosphate, glycogen, oxygen, and free fatty acids); the accumulation of metabolites (lactate/hydrogen ions, calcium, ammonium, electrolyte and water shifts); and, the special case of eccentric work. The results of many studies using various methodologies are examined. Peripheral fatigue appears to be a complex series of interactions with variable influence on the development of fatigue depending upon the nature of the work performed.
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PMID:Biochemical aspects of peripheral muscle fatigue. A review. 264 71

In an effort to determine the effects of bicarbonate (NaHCO3) ingestion on exercise performance, ten male college swimmers were studied during five different trials. Each trial consisted of five 91.4 m (100-yd) front crawl swims with a two-minute rest interval between each bout. The trials consisted of two NaHCO3 treatments, two placebo trials and one test with no-drink. One hour before the onset of swimming, the subjects were given 300 ml of citric acid flavored solution containing either 17 mmol of NaCl (placebo) or 2.9 mmol of NaHCO3.kg-1 body weight (experimental), or received no drink (no-drink). Performance times for each 91.4 m swim were recorded. Blood samples were obtained before and one hr after treatment, two min after warmup, and two min after the final 91.4 m sprint. Blood pH, lactate, standard bicarbonate (SBC) and base excess (BE) were measured. No differences were found for performance or the blood measurements between the placebo and no-drink trials. Bicarbonate feedings, on the other hand, produced a significant (P less than 0.05) improvement in performance on the fourth and fifth swimming sprints. Blood lactate, pH, SBC and BE were significantly higher (P less than 0.05) at post-exercise in NaHCO3 treatments. These data are in agreement with previous findings that during repeated bouts of exercise pre-exercise administration of NaHCO3 improves performance, possibly by facilitating the efflux of hydrogen ions from working muscles and thereby delaying the onset of fatigue.
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PMID:Sodium bicarbonate ingestion improves performance in interval swimming. 284 39

H+ ions are generated rapidly when muscles are maximally activated. This results in an intracellular proton load. Typical proton loads in active muscles reach a level of 20-25 mumol X g-1, resulting in a fall in intracellular pH of 0.3-0.5 units in mammalian muscle and 0.6-0.8 units in frog muscle. In isolated frog muscles stimulated to fatigue a proton load of this magnitude is developed, and at the same time maximum isometric force is suppressed by 70-80%. Proton loss is slowed when external pH is kept low. This is paralleled by a slow recovery of contractile tension and seems to support the idea that suppression results from intracellular acidosis. Nonfatigued muscles subjected to similar intracellular proton loads by high CO2 levels show a suppression of maximal tension by only about 30%. This indicates that only a part of the suppression during fatigue is normally due to the direct effect of intracellular acidosis. Further evidence for a component of fatigue that is not due to intracellular acidosis is provided by the fact that some muscle preparations (rat diaphragm) can be fatigued with very little lactate accumulation and very low proton loads. Even under these conditions, a low external pH (6.2) can slow recovery of tension development 10-fold compared with normal pH (7.4). We must conclude that there are at least two components to fatigue. One, due to a direct effect of intracellular acidosis, acting directly on the myofibrils, accounts for a part of the suppression of contractile force. A second, which in many cases may be the major component, is not dependent on intracellular acidosis. This component seems to be due to a change of state in one or more of the steps of the excitation-contraction coupling process. Reversal of this state is sensitive to external pH which suggests that this component is accessible from the outside of the cell.
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PMID:The effect of acid-base balance on fatigue of skeletal muscle. 299 67

Muscle fatigue, defined as a decreased force generating capacity, develops gradually during exercise and is distinct from exhaustion, which occurs when the required force or exercise intensity can no longer be maintained. We have reviewed several biochemical and ionic changes reported to occur in exercising muscle, and analysed the possible effects these changes may have on the electrical and contractile properties of the muscle. There is no evidence that substrate depletion can account for the decreased force generating capacity, but this factor may be important for the rate of energy turnover and be a major determinant for endurance. Increased concentration of inorganic phosphate and hydrogen ions will depress the force generating capacity, but since fatigue can develop gradually without accumulation of these ions they can only be important when aerobic ATP production is insufficient to support the contractions. Evidence is presented showing that a disturbed balance of K+ alone might cause depolarisation block at high stimulation frequencies, but extracellular K+ accumulation does not increase gradually during prolonged dynamic or static exercise, and is therefore not closely related to fatigue. The repeated release of Ca2+ from the sarcoplasmic reticulum (SR) during muscular activity is suggested of Ca2+ by the mitochondria, increasing with stimulation frequency and duration and possibly also deteriorating mitochondrial function. We therefore speculate that decreased Ca2+ availability for release from SR might contribute to a gradual decline in force generating capacity during all types of exercise.
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PMID:Biochemical correlates of fatigue. A brief review. 328 52

During muscular fatigue two metabolites, hydrogen ions (H+) and inorganic phosphate (Pi), increase in concentration. The effect of increase in [H+] has been modeled mathematically for a system containing creatine kinase (EC 2.7.3.2), adenylate kinase (EC 2.7.4.3), and the appropriate concentrations of their substrates. Assuming that no other equilibrium reactions are involved, the result of acidification should be a useful increase in the ratio [ATP]/[ADP]. It is also shown by a reanalysis of earlier 31P NMR studies that the observed combination of increased [H+] and increased [Pi] leads to an increase in the monobasic phosphate concentration [Pi-] that is inversely proportional to the force of contraction. This suggests that Pi- may be a direct inhibitor of the actomyosin ATPase system.
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PMID:Muscular fatigue: effects of hydrogen ions and inorganic phosphate. 353 90

The increases in the intracellular concentrations of inorganic phosphate and hydrogen ion accompanying fatigue of skeletal muscle appear to be the most important metabolic changes associated with the decrease in contractile force. Experiments on chemically skinned single fibers from rabbit psoas muscle with pH ranging between 6 and 7.25 demonstrate that the depression of maximal calcium-activated force by inorganic phosphate correlates nicely with the concentration of the acidic (diprotonated) species. Therefore, in addition to the well-known depressant effect on the contractile machinery of lowering pH per se, any decrease of intracellular pH associated with fatigue further depresses force production by converting more of the total inorganic phosphate within the cell to the inhibitory diprotonated form.
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PMID:It is diprotonated inorganic phosphate that depresses force in skinned skeletal muscle fibers. 356 96


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