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

To differentiate the effects of high energy phosphates, pH, and [H2PO4-] on skeletal muscle fatigue, intracellular acidosis during handgrip exercise was attenuated by prolonged submaximal exercise. Healthy human subjects (n = 6) performed 5-min bouts of maximal rhythmic handgrip (RHG) before (CONTROL) and after prolonged (60-min) handgrip exercise (ATTEN-EX) designed to attenuate lactic acidosis in active muscle by partially depleting muscle glycogen. Concentrations of free intracellular phosphocreatine ([PCr]), adenosine triphosphate ([ATP]), and orthophosphate ([P(i)]) and pH were measured by 31P nuclear magnetic resonance spectroscopy and used to calculate adenosine diphosphate [ADP], [H2PO4-], and [HPO4(2-)]. Handgrip force output was measured with a dynamometer, and fatigue was determined by loss of maximal contractile force. After ATTEN-EX, the normal exercise-induced muscle acidosis was reduced. At peak CONTROL RHG, pH fell to 6.3 +/- 0.1 (SE) and muscle fatigue was correlated with [PCr] (r = 0.83), [P(i)] (r = 0.82), and [H2PO4-] (r = 0.81); [ADP] was 22.0 +/- 5.7 mumol/kg. At peak RHG after ATTEN-EX, pH was 6.9 +/- 0.1 and [ADP] was 116.1 +/- 18.2 mumol/kg, although [PCr] and [P(i)] were not different from CONTROL RHG (P greater than 0.05). After ATTEN-EX, fatigue correlated most closely with [ADP] (r = 0.84). The data indicate that skeletal muscle fatigue 1) is multifactorial, 2) can occur without decreased pH or increased [H2PO4-], and 3) is correlated with [ADP] after exercise-induced glycogen depletion.
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PMID:Human muscle fatigue after glycogen depletion: a 31P magnetic resonance study. 150 2

Effects of an infusion of Na2HPO4 on diaphragm strength, endurance, and magnitude of recovery were evaluated in in situ canine diaphragm strips. Results showed no effect on maximal isometric tetanic tension. Twitch tension and tension in the low- (10-Hz) frequency range were significantly increased (P less than 0.01). Time to fatigue (endurance) increased by 38 +/- 4.5% in the group that received phosphorus compared with its control and decreased by 18.5 +/- 2.5% in the group that received dextrose compared with its control (P less than 0.005). Recovery from fatigue was also significantly improved after the phosphorus infusion. Serum ATP and 2,3-diphosphoglycerate levels were unchanged throughout the experiment. The results of this study support the notion that hyperphosphatemia improves diaphragmatic endurance and recovery from fatigue. The mechanisms involved may in part be due to the phosphate-buffering effects, which limit the extent of the muscle intracellular acidosis produced with fatigue.
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PMID:Effects of hyperphosphatemia on diaphragmatic strength and endurance. 150 3

Endurance muscle performance is highly dependent on ATP production from mitochondrial oxidative phosphorylation. To study the role of the mitochondrial oxidative enzymes in muscle fatigue, we analyzed the relationship between the concentrations of substrates associated with ATP synthesis and the muscle performance of electrically stimulated rabbit muscle under CO2-induced acidosis. Two different conditions of pacing-induced muscle performance were produced in the gastrocnemius and soleus muscle groups in anesthetized rabbits by stimulating the sciatic nerve submaximally at two frequencies. Phosphorus nuclear magnetic resonance was used to measure ATP, phosphocreatine, and Pi and to provide data for a calculation of intracellular pH and free ADP. To induce acidosis, the animal was ventilated with 20% CO2. The administration of CO2 effectively reduced the intracellular pH from 6.9 to 6.7 and reduced the isometric tension-time integral (TTI) to below half the value measured in normocapnia at the low pacing frequency. A twofold increase in the pacing frequency resulted in a doubling of the TTI in normocapnia and a tripling of TTI in hypercapnia. The increases in TTI corresponded with increases in free ADP and Pi concentrations. Under the various conditions, all free ADP values were near the in vitro Michaelis-Menten constant (Km) of ADP. The Michaelis-Menten relationship of the oxidative phosphorylative enzymes was applied to the change in substrate concentrations with respect to TTI. From this relationship we observed that the in vivo Km of free ADP was 26 microM, which is close to the in nitro Km, and that Km and maximal reaction velocity did not change under hypercapnia and increased pacing frequency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substrate regulation of mitochondrial oxidative phosphorylation in hypercapnic rabbit muscle. 155 27

The supply of energy is of fundamental importance for the ability to sustain exercise. The maximal duration of exercise is negatively related to the relative intensity both during dynamic and static exercise. Since exercise intensity is linearly related to the rate of energy utilisation this suggests that energetic deficiency plays a major role in the aetiology of muscle fatigue. Characteristic metabolic changes in the muscle are generally observed at fatigue--the pattern being different after short term exercise (lactate accumulation and phosphocreatine depletion) from after prolonged exercise at moderate intensity (glycogen depletion). A common metabolic denominator at fatigue during these and many other conditions is a reduced capacity to generate ATP and is expressed by an increased catabolism of the adenine nucleotide pool in the muscle fibre. Transient increases in ADP are suggested to occur during energetic deficiency and may be the cause of fatigue. Experimental evidence from human studies demonstrate that near maximal power output can be attained during acidotic conditions. Decreases in muscle pH is therefore unlikely to affect the contractile machinery by a direct effect. However, acidosis may interfere with the energy supply possibly by reducing the glycolytic rate, and could by this mechanism be related to muscle fatigue.
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PMID:Metabolic factors in fatigue. 156 13

1. Peak isometric force of single fast (type 1) and slow (type 3) muscle fibres of Xenopus decreased when fibres were stimulated intermittently above their predicted sustainable duty cycle at 20 degrees C. Type 1 fibres could be fatigued to zero force. In most type 3 fibres force did not decrease below 50% of the original (P0) before activation failure, as indicated by irregular contractions. 2. Fibres were rapidly frozen at different force levels and analysed by high-performance liquid chromatography (HPLC) for ATP, IMP, phosphocreatine (PCr) and creatine (Cr). Lactate was determined enzymatically in type 1 fibres only. The relationships between force and PCr, and between force and ATP during fatigue were, apart from the range of values obtained, the same for both fibre types. When force had fallen to about 60-80% of original, PCr was fully reduced. At lower force levels, the ATP content-decreased, and a concomitant rise of IMP content was found. At zero force, ATP had fallen to about 25% of its value in rested type 1 fibres, and up to 200 mumol lactate (g dry weight)-1 had accumulated. 3. Recovery from fatigue was studied in fibres where force had fallen to 0.6 P0 (both fibre types) and 0.2 P0 (type 1 only). After 1 h of recovery ATP had in all cases returned to the level measured in rested fibres. In fibres fatigued to 0.6 P0, force almost returned to its original value. However, in type 1 fibres fatigued to 0.2 P0, it returned to only 0.3 P0. After 1 h of recovery the PCr/Cr ratio in type 1 fibres was lower (probability, P less than 0.05) than in control fibres, whereas in type 3 fibres it was not significantly different from controls. 4. The relationship between peak force and stimulus frequency, which had a sigmoid shape in fully rested fibres, was drastically changed by fatiguing stimulation. Immediately after fatiguing stimulation of type 1 fibres, force hardly increased with stimulus frequency, corresponding to the observation that calcium efflux from the sarcoplasmic reticulum was decreased at high stimulus frequencies. The force-frequency relationship of type 3 fibres was the same before and after intermittent stimulation.
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PMID:Metabolic changes with fatigue in different types of single muscle fibres of Xenopus laevis. 159 75

A novel, simple, rapid and reproducible microassay is used for kinetic analysis of Ca-sequestration by homogenates of myocardium of turkeys with furazolidone-induced congestive cardiomyopathy. The assay monitors Ca in real-time using dual-emission ratiometric spectrofluorometry and the Ca-indicator dye indo-1. Using this assay and isolated SR studies we make several novel findings regarding the mechanism of SR failure in furazolidone cardiomyopathy. Qualitative differences in Ca-sequestration were not detected between groups. However, compared to controls the furazolidone treatment resulted in: 1) 50% depression in maximal activities (1.54 +/- 0.36 vs 0.73 +/- 0.12 microM/sec); 2) 2-fold increases in post-sequestration concentrations of ionized Ca (79 +/- 23 vs 141 +/- 13 nmol Ca/L homogenate); 3) 2-fold increases in Ca half-life (415 vs 790 msec); and 4) 25% increased passive Ca-binding capacity of homogenates. The Ca-ATPase specific activity of isolated sarcoplasmic reticulum was 60% increased in congestive cardiomyopathy (543 +/- 140 vs 873 +/- 108 nmol ATP hydrolyzed/min/mg membrane protein) although membrane yield was 20% decreased (0.79 +/- 0.09 vs 0.63 +/- 0.03 mg/g heart). The increased ATPase and decreased Ca-uptake activities in combination with the occurrence of 36% cardiac hypertrophy and 19% decreased body weights resulted in estimates of the relative energy cost to the animal for myocardial Ca transport being 5.5-fold increased with cardiomyopathy (20.5 vs 111 nmol ATP hydrolyzed per microM decrease of sarcoplasmic free Ca/kg body weight). These data indicate that congestive cardiomyopathy is associated with markedly increased permeability of sarcoplasmic reticulum to Ca and compensatorily increased Ca-ATPase activity. Accelerated energy consumption due to the increased energy cost of Ca transport and increased time of myocyte activation are predicted to predispose the myocardium to fatigue and irreversible failure.
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PMID:Myocardial Ca-sequestration failure and compensatory increase in Ca-ATPase with congestive cardiomyopathy: kinetic characterization by a homogenate microassay using real-time ratiometric indo-1 spectrofluorometry. 182 61

This report describes how the resistance to fatigue of a muscle fibre relates to the fibre's most important ATP-producing and ATP-consuming reactions. Twelve intact single muscle fibres were dissected from lumbrical muscles of Xenopus laevis. Their resistance to fatigue induced by repeated tetanic stimulation was determined, as well as their succinate dehydrogenase activity and calcium-stimulated myofibrillar ATPase activity. The enzyme activities were determined by means of quantitative histochemistry. It was found that resistance to fatigue correlates with succinate dehydrogenase activity (r = 0.83) and with myofibrillar ATPase activity (r = -0.74). The highest correlation was found between resistance to fatigue and the ratio of succinate dehydrogenase to myofibrillar ATPase activity (r = 0.93). It is concluded that muscular fatigue is closely related to cellular energetics.
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PMID:Resistance to fatigue of single muscle fibres from Xenopus related to succinate dehydrogenase and myofibrillar ATPase activities. 183 77

Two metabolic features of altitude-adapted humans are the maximal O2 consumption (VO2max) paradox (higher work rates following acclimatization without increases in VO2max) and the lactate paradox (progressive reductions in muscle and blood lactate with exercise at increasing altitude). To assess underlying mechanisms, we studied six Andean Quechua Indians in La Raya, Peru (4,200 m) and at low altitude (less than 700 m) immediately upon arrival in Canada. The experimental strategy compared whole-body performance tests and single (calf) muscle work capacities in the Andeans with those in groups of sedentary, power-trained, and endurance-trained lowlanders. We used 31P nuclear magnetic resonance spectroscopy to monitor noninvasively changes in concentrations of phosphocreatine [( PCr]), [Pi], [ATP], [PCr]/[PCr] + creatine ([Cr]), [Pi]/[PCr] + [Cr], and pH in the gastrocnemius muscle of subjects exercising to fatigue. Our results indicate that the Andeans 1) are phenotypically unique with respect to measures of anaerobic and aerobic work capacity, 2) despite significantly lower anaerobic capacities, are capable of calf muscle work rates equal to those of highly trained power- and endurance-trained athletes, and 3) compared with endurance-trained athletes with significantly higher VO2max values and power-trained athletes with similar VO2max values, display, respectively, similar and reduced perturbation of all parameters related to the phosphorylation potential and to measurements of [Pi], [PCr], [ATP], and muscle pH derivable from nuclear magnetic resonance. Because the lactate paradox may be explained on the basis of tighter ATP demand-supplying coupling, we postulate that a similar mechanism may explain 1) the high calf muscle work capacities in the Andeans relative to measures of whole-body work capacity, 2) the VO2max paradox, and 3) anecdotal reports of exceptional work capacities in indigenous altitude natives.
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PMID:Skeletal muscle metabolism and work capacity: a 31P-NMR study of Andean natives and lowlanders. 186 76

Blood adenine nucleotides were determined in patients with alcoholic and non-alcoholic liver diseases. They included patients with alcoholic hepatitis (AH), alcoholic liver cirrhosis (ALC), non-alcoholic liver cirrhosis (NALC), and amoebic liver abscess (ALA) (28 patients). A decrease of 28% to 39% in blood ATP levels was observed among the patients with AH and the cirrhotic groups, respectively (p less than 0.05), whereas no significant changes in blood ATP levels were detected in the ALA group. Although total blood adenine nucleotides were significantly diminished in AH, ALC, and NALC groups, the AH patients retained their energy relationships within normal range. On the other hand, the cirrhotic groups, independently of their etiology, failed to maintain an adequate ATP/ADP ratio, energy charge, and phosphorylation potential in the blood, suggesting a decreased energy availability in their blood cells. Nevertheless, the mechanism involved in these effects remains to be elucidated, a failure of the damaged liver to supply purines to extra-hepatic tissues might be a major event altering the blood energy parameters.
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PMID:Alterations of ATP levels and of energy parameters in the blood of alcoholic and nonalcoholic patients with liver damage. 187 35

The sublethal biochemical effects of pentachlorophenol (PCP) were investigated in live, intact red abalones (Haliotis rufescens), using a flow-through exposure system, by in vivo 31P NMR spectroscopy. Based on rangefinding tests (6-hr LC50 = 1.6 mg/L; 6-hr no-observable-effect-level (NOEL) = 0.8 mg/L), three abalones were separately exposed to a sublethal concentration (1.2 mg/L) for 5 hr, followed by a 13 hr recovery period. Effects in foot muscle included both a decrease in phosphoarginine and an increase in inorganic monophosphate concentrations ([PA] and [Pi], respectively); both foot muscle concentrations of adenosine triphosphate [ATP] and intracellular pH (pHi) also declined. Parallel in vitro experiments revealed that concentrations of glycerol 3-phosphate, lactate, citrate, succinate, malate, and alanine (Ala) all increased, while those of glyceraldehyde 3-phosphate and glutamine (Gln) remained stable. Also, these effects were not evident until 2 hr into exposure, possibly the time required for PCP to attain an effective concentration in foot muscle. During recovery, while Pi declined to pre-exposure levels, [PA] completely recovered in only one individual. Also, realkalinization of pHi was similar to recovery of [Pi], and ATP returned to near-initial levels, as did glycerol 3-phosphate, lactate, succinate, malate, and Ala; glyceraldehyde 3-phosphate, citrate, and Gln levels declined. Recovery responses corresponded to the time for PCP clearance from foot muscle. The effects of PCP were similar to those of hypoxia, fatigue, hypersalinity, and arginine kinase inhibitors, and so sublethal PCP concentrations may also inhibit electron transport and arginine kinase as well as uncouple mitochondrial oxidative phosphorylation in intact molluscs. Thus, the effects of pollutants on key biochemical processes may now be measured in intact aquatic organisms as they occur, improving our ability to accurately assess the environmental effects of pollutants in the laboratory.
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PMID:Sublethal effects of pentachlorophenol in the abalone (Haliotis rufescens) as measured by in vivo 31P NMR spectroscopy. 188 Jul 88


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