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

Chronic administration of the NADH-CoQ reductase inhibitor, diphenyleneiodonium to rats at two dose levels, 1.0 and 1.5 mg/kg per day, caused a 40% and 60% reduction, respectively, in the in vitro rate of NAD-linked respiration by skeletal muscle mitochondria. At the highest dose, muscle fatigue, lactic acidosis and an over-utilization of phosphocreatine was observed in the gastrocnemius muscle during mild stimulation of 1 Hz frequency. The resynthesis of phosphocreatine following muscle stimulation was about 2 fold slower in the treated animal group. At the low dose, no significant biochemical changes were observed during muscle stimulation at 4 Hz. The results are discussed in terms of skeletal muscle "oxidative reserve", twitch tension maintenance and the relevance to the human diseased state of mitochondrial myopathy.
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PMID:An animal model of mitochondrial myopathy: a biochemical and physiological investigation of rats treated in vivo with the NADH-CoQ reductase inhibitor, diphenyleneiodonium. 312 47

Metabolite changes in the costal diaphragm were determined in anesthetized dogs subjected to a moderate inspiratory elastic load and to reduced blood flow. Diaphragmatic blood flow was reduced by occlusion of the descending aorta and internal mammary arteries. The goal of this study was to demonstrate that the failing diaphragm under these conditions shows biochemical changes similar to that of skeletal muscle fatigue. Selected metabolite concentrations were determined 1) during mechanical ventilation and normal blood flow, 2) during blood flow reduction and inspiratory loading when the ratio of airway pressure to diaphragmatic electromyogram (Paw/Edi) had decreased by 50% (fatigue), and 3) at 1 h after restoration of blood flow and mechanical ventilation (recovery). During fatigue, glycogen, ATP, and phosphocreatine were 30, 50, and 50% of control levels, respectively. Glucose 6-phosphate and lactate were two- and fivefold higher, respectively, than control concentrations. During recovery, all metabolites, except ATP and lactate, returned to control concentrations. These changes were not seen in resting ischemic skeletal muscles or in the diaphragmatic samples of the mechanically ventilated animals with diaphragmatic blood flow limitation. We conclude that when the loaded and hypoperfused diaphragm fails, as indicated by lower than control Paw/Edi, metabolite changes similar to that observed in fatigued skeletal muscle occur.
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PMID:Metabolite changes in the loaded hypoperfused and failing diaphragm. 314 59

Force generation and ATP utilization under anaerobic conditions were studied in the quadriceps femoris muscle of six volunteers. Electrical stimulation (20 Hz) was used to produce contractions with a duration of 0.8 s in one leg and contractions with a duration of 3.2 s in the other leg. The two procedures were designed to give the same total contraction time of 51 s and used the same number of stimulation pulses. Muscle biopsies were taken at rest and after 22 and 51 s of work and analyzed for ATP, phosphocreatine, and glucolytic intermediates. The results were compared with previous studies on continuous and intermittent stimulation. Fatigue developed significantly faster with contractions of short duration, and the energy cost was higher. Since force at the end of stimulation had a negative correlation to ATP utilization, there is no indication that the energy resources limit force generation. By comparison of stimulations producing the same amount of isometric work but with a different number of contractions, we estimate that the energy cost for activation and relaxation of a 1-s contraction is approximately 37% of the total ATP consumption.
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PMID:Energy cost and fatigue during intermittent electrical stimulation of human skeletal muscle. 318 13

Patients with heart failure frequently report leg fatigue during exercise. At present, however, there is no objective method of detecting leg muscle abnormalities in such patients. To determine if phosphorus-31 nuclear magnetic resonance spectroscopy can provide such information, this technique was used to compare calf responses to stair climbing and plantarflexion in 20 patients with heart failure (peak oxygen consumption (VO2) of 13.6 +/- 5 ml/kg/min, ejection fraction 20 +/- 5%) and 9 age-matched normal subjects. Work was quantified by measuring VO2. At rest, both groups exhibited similar inorganic phosphorus to phosphocreatine (Pi/PCr) ratios (patients with heart failure 0.21 +/- 0.07, normal subjects 0.21 +/- 0.06, difference not significant) and pH levels (patients with heart failure 7.06 +/- 0.17, normal subjects 7.05 +/- 0.11, difference not significant). In both normal subjects and patients with heart failure, exercise resulted in a progressive rise in Pi/PCr as VO2 increased. However, examination of the relation of VO2 versus Pi/PCr revealed steeper slopes in patients with heart failure during both stair climbing and plantar-flexion. Neither form of exercise decreased calf pH in normal subjects. In the patients with heart failure, significant decreases in pH were noted during the highest work level of plantarflexion (pH of heart failure patients 6.86 +/- 0.20, pH of normal subjects 7.07 +/- 0.14, p less than 0.01). Metabolic recovery time was also prolonged in the patients with heart failure versus normal subjects (3.3 +/- 0.8 vs 2.1 +/- 0.5 minutes, respectively, p less than 0.002). These findings indicate that phosphorus-31 nuclear magnetic resonance provides objective evidence of leg muscle abnormalities in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of abnormal calf muscle metabolism in patients with heart failure using phosphorus-31 nuclear magnetic resonance. 319 84

Denervated (1-10 days) rat epitrochlearis muscles were isolated, and basal and insulin-stimulated protein and glucose metabolism were studied. Although basal rates of glycolysis and glucose transport were increased in 1-10-day-denervated muscles, basal glycogen-synthesis rates were unaltered and glycogen concentrations were decreased. Basal rates of protein degradation and synthesis were increased in 1-10-day-denervated muscles. The increase in degradation was greater than that in synthesis, resulting in muscle atrophy. Increased rates of proteolysis and glycolysis were accompanied by elevated release rates of leucine, alanine, glutamate, pyruvate and lactate from 3-10-day-denervated muscles. ATP and phosphocreatine were decreased in 3-10-day-denervated muscles. Insulin resistance of glycogen synthesis occurred in 1-10-day denervated muscles. Insulin-stimulated glycolysis and glucose transport were inhibited by day 3 of denervation, and recovered by day 10. Inhibition of insulin-stimulated protein synthesis was observed only in 3-day-denervated muscles, whereas regulation by insulin of net proteolysis was unaffected in 1-10-day-denervated muscles. Thus the results demonstrate enhanced glycolysis, proteolysis and protein synthesis, and decreased energy stores, in denervated muscle. They further suggest a defect in insulin's action on protein synthesis in denervated muscles as well as on glucose metabolism. However, the lack of concurrent changes in all insulin-sensitive pathways and the absence of insulin-resistance for proteolysis suggest multiple and specific cellular defects in insulin's action in denervated muscle.
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PMID:Resistance of protein and glucose metabolism to insulin in denervated rat muscle. 319 84

The mechanism of muscle fatigue was studied by 31P-MRS. During tetanic contraction for 2 minutes(min), the tension measured with a strain gauge and Phosphocreatine(PCr)/Inorganic phosphate(Pi)+ Phosphomonoester(PME) ratio decreased to 31.5 +/- 4.4% of the control value and 0.6 +/- 0.1, respectively. The intracellular pH(pH) also decreased to 6.62 +/- 0.04. Toward the end of the stimulation, the tension decreased to 25.3 +/- 1.9% of the control value. However, during 20min stimulation, the PCr/(Pi+PME) ratio increased to 2.5 +/- 0.5 and the pH to 6.91 +/- 0.04. These results show that muscular fatigue is ascribable not to a decreased level of high energy metabolites required for actomyosin ATPase, but to an increase in the threshold intensity of excitation in excitation-contraction coupling.
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PMID:Observation of fatigue unrelated to gross energy reserve of skeletal muscle during tetanic contraction--an application of 31P-MRS. 319 34

Changes in isometric force, power output and relaxation rate have been measured during repetitive tetanic contractions in 2 groups of rats of different ages. During the first 5 contractions there were no differences between a young and mature group. In contrast to isometric force production, which decreased about 3% per contraction, power output initially increased to 108% of the power output in the first contraction. A greater reduction in power output and relaxation rate after the 5th contraction indicated a greater reduction of the cross-bridge cycling rate in the younger rats. ATP, phosphocreatine and lactate concentrations after the last contraction were not different between the age-groups. In contrast IMP production, which has been suggested may play a regulatory role during fatigue was twice as high in the young rats. Judged by isometric force production there is no age-related difference in fatiguability. However, profound differences were observed in power output, which indicates that quantification of fatigue as a loss of isometric force may be seriously misleading when considering the functional status of the muscle for normal dynamic contractions.
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PMID:Age-related changes in power output during repetitive contractions of rat medial gastrocnemius muscle. 321 17

Phosphorus nuclear magnetic resonance (31P NMR) spectroscopy is a non-destructive analytical laboratory technique that, due to recent technical advances, has become applicable to the study of high-energy phosphate metabolism in both animal and human extremity muscles (in vivo). 31P NMR can assay cellular phosphocreatine, ATP, inorganic phosphate, the phosphorylated glycolytic intermediates, and intra-cellular pH in either resting or exercising muscle, in a non-invasive manner. NMR uses non-perturbing levels of radio-frequency energy as its biophysical probe and can therefore safely study intact muscle in a repeated fashion while exerting no artifactual influence on ongoing metabolic processes. Compared with standard tissue biopsy and biochemical assay techniques, NMR possesses the advantages of being non-invasive, allowing serial in situ studies of the same tissue sample, and providing measurements of only active (unbound) metabolites. NMR studies of exercising muscle have yielded information regarding fatigue mechanisms at the cellular level and are helping resolve long-standing questions regarding the metabolic control of glycolysis, oxidative phosphorylation, and post-exercise phosphocreatine re-synthesis. NMR is also being utilized to measure enzymatic reaction rates in vivo. In the near future, other forms of NMR spectroscopy may also permit the non-invasive measurement of tissue glycogen and lactate content.
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PMID:Phosphorus nuclear magnetic resonance: a non-invasive technique for the study of muscle bioenergetics during exercise. 330 42

Chronic stimulation converts skeletal muscle of mixed fiber type to a uniform muscle made up of type I, fatigue-resistant fibers. Here, the bioenergetic correlates of fatigue resistance in conditioned canine latissimus dorsi are assessed with in vivo phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy. After chronic electrical stimulation, five dogs underwent 31P-NMR spectroscopic and isometric tension measurements on conditioned and contralateral control muscle during stimulation for 200, 300, 500, and 800 ms of an 1,100-ms duty cycle. With stimulation, phosphocreatine (PCr) fell proportional to the degree of stimulation in both conditioned and control muscle but fell significantly less in conditioned muscle at all but the least intense stimulation period (200 ms). Isometric tension, expressed as a tension time index per gram muscle, was significantly greater in the conditioned muscle at the two longest stimulation periods. The overall small change in PCr and the lack of a plateau in tension observed in the conditioned muscle are similar to that seen in cardiac muscle during increased energy demand. This study indicates that the conditioned muscle's markedly enhanced resistance to fatigue is in part the result of its increased capacity for oxidative phosphorylation.
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PMID:In vivo 31P-NMR spectroscopy of chronically stimulated canine skeletal muscle. 334 65

The goal of these experiments was to investigate the relationship of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), monobasic phosphate (H2PO4-), and pH to human muscle fatigue. Phosphates and pH were measured in adductor pollicis using 31P nuclear magnetic resonance at 2.0 Tesla. The force of muscle contraction was simultaneously measured with a force transducer. The effects of aerobic and anaerobic exercise were compared using two exercise protocols: 4 min sustained maximal voluntary contraction (MVC) and 40 min of repeated intermittent contractions (75% MVC). The sustained maximal contraction produced a rapid decline of MVC and PCr, and was accompanied by a rapid rise of Pi, H+, and H2PO4-. Intermittent exercise produced steady state changes of MVC, pH, and phosphates. No significant changes of ATP were found in either protocol. During fatiguing exercise, PCr and Pi had a nonlinear relationship with MVC. H+ showed a more linear correlation, while H2PO4- showed the best correlation with MVC. Furthermore, the correlations between MVC and H2PO4- were similar in sustained (r = 0.70) and intermittent (r = 0.73) exercise. The highly significant linear relationship between increases of H+ and H2PO4- and the decline of MVC strongly suggests that both H+ and H2PO4- are important determinants of human muscle fatigue.
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PMID:31P nuclear magnetic resonance studies of high energy phosphates and pH in human muscle fatigue. Comparison of aerobic and anaerobic exercise. 335 Sep 69


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