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

The metabolic effects of 60-min exposure to 250-2000 mg gamma-hydroxybutyrate (GHB) per kilogram or 150-1200 mg gamma-butyrolactone (GBL) per kilogram were studied in rats by measurement of the cerebral hemisphere contents of energy phosphates and glycolytic-Krebs' cycle metabolites. A general pattern of increased glycogen and glucose with decreased pyruvate, lactate, alpha-ketoglutarate, and malate was observed. This pattern in association with unchanged adenylates and decreased energy phosphate utilization was consistent with a metabolic adaptation to a state of cerebral depression. The major qualitative difference between the two drugs was that higher doses of GBL were associated with additional decreases of citrate and glutamate. Since these doses of GBL were also associated with acute increases of arterial CO2 tension, it is proposed that these differences were secondary to hypercapnia and not due to a distinctive primary action of GBL. Derivation of the cytoplasmic NAD(P)H:NAD(P)+ ratios indicated that GHB and GBL were not associated with consistent alterations of the cytoplasmic redox state.
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PMID:A comparison of the effects of gamma-hydroxybutyrate and gamma-butyrolactone on cerebral carbohydrate metabolism. 4 Jun 77

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

The development of fatigue was investigated by electrical stimulation in 15 domestic pigs (1 yr old, 70-90 kg body weight) and seven adult dogs (3 yr old, 45 kg body weight). After anaesthesia, silver electrodes were implanted in the anterior and posterior parts of the right masseter muscles. The contralateral muscle was used as control. The bite force was measured. Muscle biopsies were obtained from the anterior, central and posterior parts, and were immediately frozen in liquid nitrogen. A fluorometrical analysis by enzymatic methods for glycogen, glucose, creatine phosphate, NAD, NADH, lactate and pyruvate was made. Blood flow was measured by 133Xe wash-out; oxygen consumption was monitored with an oxygen electrode. The porcine masseter was continuously stimulated for 60 min (100 V, 4 Hz and 2 ms). The canine masseter was intermittently stimulated (100 V, 20 Hz and 2 ms). The contraction was repeated four times, with a 10-min rest between. The porcine masseter could sustain longer endurance times than the canine masseter, which was easily fatigued. A marked substrate depletion was evident. The precontractional contents of glycogen, glucose and creatine phosphate were reduced. Lactate accumulation was evident (2-4 times more in the porcine and 4-8 times more in the canine masseter). The NADH concentration increased and the NAD content decreased. Blood-flow impairment (80% reduction in the dog, 60% in the pig) was observed. After the contraction phase, there was a hyperaemia (58% elevation of blood flow in the pig masseter, 45% in the canine). The oxygen tension followed in magnitude and time the blood-flow changes. These circulatory variables returned to normal after recovery. The high degree of substrate depletion, blood-flow impairment and a simultaneous decrease in oxygen transport to the contracted muscle, in combination with a prominent lactate accumulation, may induce a decrease in bite-force production.
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PMID:Bite-force development, metabolic and circulatory response to electrical stimulation in the canine and porcine masseter muscles. 147 60

Inhibition of endogenous long chain fatty acids oxidation by tetradecylglycidate (TDGA) impeded gluconeogenesis from lactate or from low concentrations of pyruvate (less than 0.5 mM). The inhibitory effect of TDGA was overcome by medium and short chain fatty acid or by concentrations of pyruvate about 0.5 mM, but not by 10-fold higher concentrations of lactate. Despite decreased energy demand when gluconeogenesis was inhibited by TDGA, the pyruvate-induced increase in hepatic oxygen consumption was similar to the control, indicating that pyruvate transport across the mitochondrial membrane and/or its decarboxylation was not altered, and therefore can not be responsible for the inhibition of gluconeogenesis. Neither does a deficiency of acetyl-CoA explain the decrease in the gluconeogenic flux since high pyruvate loads (greater than 0.5 mM), beta-hydroxybutyrate or even ethanol was capable of overcoming the inhibitory effect of TDGA in the absence of significant changes in the hepatic content of acetyl-CoA. At low (less than 0.3 mM), presumably physiological, pyruvate concentrations, its rate of mitochondrial utilization is limited by the activity of the monocarboxylate transporter. Agents that reduced the mitochondrial NAD system, and therefore reduced flux through pyruvate dehydrogenase, like beta-hydroxybutyrate or ethanol, stimulated gluconeogenesis when fatty acid oxidation was inhibited. The latter observations indicate that the primary role of endogenous fatty acid, when substrate availability is limiting, is to spare mitochondrial pyruvate by decreasing its oxidation, and therefore shifting the partitioning between the carboxylation and decarboxylation reactions toward the former.
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PMID:Role of endogenous fatty acids in the control of hepatic gluconeogenesis. 172 53

A study was made of the role of prolactin (PRL) in the regulation of thyroid function in intact animals and in those exposed to stress (swimming was used as physical exercise). A single daily dose of 125 micrograms of PRL per 100 g of body mass was injected subcutaneously in 0.5 ml of saline solution during a week to male rats (control: intact rats; injection of 0.5 ml of saline solution subcutaneously). Redox enzymes; succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, NAD.H2 and NADP.H2, ATPase and monoamine oxidase, total protein, RNA and glycogen in glandular cells were investigated histochemically 24 h after the last injection of PRL or saline, 30 min., 1, 2, 3, 5 and 7 hours after swimming or right after complete fatigue (in the presence of experimental hyperprolactinemia). A conclusion has been made that one of the most important mechanisms of the adaptive effect of PRL is its ability to suppress thyroid function, thus decreasing the metabolism level, which results in reduction of oxygen consumption and improves body tolerance to stress.
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PMID:[Metabolism of thyroid gland cells as affected by prolactin and emotional-physical stress]. 178 Feb 95

The aim of this thesis was to characterize structural factors in masticatory systems relevant to functional evaluations and to elucidate the effect on energy metabolism of electrically induced jaw muscle fatigue. An omnivorous masticatory system (the domestic pig) was compared morphologically with a carnivorous (the dog). Porcine masseter muscles were evaluated by ATP-ase histochemistry as well as with NADH-dehydrogenase and PAS-staining. Contractional characteristics were obtained from the porcine and canine masseters by electrical stimulation. The 133Xenon clearance technique and a flexible oxygen electrode were employed. A bite-force transducer was used. The porcine craniomandibular joint (CMJ) lacked a pronounced mandibular fossa and had anteriorly orientated cylindrical condyles. The dog CMJ comprised a cylindrical condyle orientated at right angles to the satittal plane and medially inclined. The pronounced mandibular fossa and marked tubercle, together with a well-developed retro-articular process, surrounded the condyle. The masticatory muscles were the same in the two species, except for the pig's zygomatico-mandibular muscle. The ATP-ase technique failed to reveal type II:B-fibres in the porcine masseter after acid and alkaline preincubation and it was not possible to separate fibre types by glycogen-staining and NADH-dehydrogenase histochemistry. These findings diverged from the pig soleus histochemical profile (type II:B-fibres 60%). The quantitative evaluation revealed 75% type II:A-fibres in the porcine masseter. No statistically significant difference was found between the various fibre-type diameters in the porcine masseter. The mean fibre Type diameter was larger in the porcine masseter than in the soleus muscle. Type II-fibres were more frequently found on the edge of the fascicles. The bite force recordings showed that the porcine masseter was capable of long endurance performance, in contrast to the easily fatigued canine masseter. Significant reductions of intramuscular substrates and a considerable lactate accumulation were observed. The NADH/NAD-shuttle was oppositely directed in the two species. The blood-flow recordings revealed a marked blood-flow impairment during contraction, followed by a prominent post-exercise hyperaemia. The pO2 recordings were closely related in time as well as in mangnitude to the blood flow. It is thus concluded, based on morphological observations, that the porcine masticatory system bears resemblance to the human situation. In the canine masseter muscle, a relationship was found between metabolism and mechanical bite-force output. This correlation was not so evident in the porcine masseter. Induced jaw muscle hyperactivity may lead to a reduced energy and redox state and, as a late consequence, to fatigue.
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PMID:Masseter muscle performance. Significance of structure and metabolism. A morphological and experimental study. 232 43

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

In the process of defining the recruitment of fuel and pathway selection in rainbow trout fast-twitch white skeletal muscle, it was clear that the near-maximal myosin adenosinetriphosphatase activity during a 10-s sprint was supported solely by phosphocreatine hydrolysis. A conservative estimate of the ATP turnover was 188 mumol X g wet wt-1 X min-1. It was not until the rate and force of contraction decreased that the relative contribution of anaerobic glycogenolysis became increasingly important. Over a 10-min period of burst swimming at approximately 120% of maximum aerobic steady-state swimming velocity of trout determined in a Brett-type swim tunnel, fatigue was associated with the near-depletion of glycogen in white muscle. The ATP turnover supported by anaerobic glycogenolysis was 78 mumol X g wet wt-1 X min-1. The glycolytic pathway appeared functional at this time with control sites being identified at hexokinase and phosphofructokinase (PFK-1). PFK-1 did not appear to be inhibited by low muscle pH (pH 6.66). In another exercise protocol lasting 30 min, complete exhaustion was related to glycogen depletion. The sum of all glycolytic intermediates from glucose 6-phosphate to pyruvate at exhaustion decreased by a dramatic 80% compared with the 25% decrease for the 10-min fatigue swimming protocol. This large depletion of glycolytic intermediates was accompanied by an 80% fall in ATP, a 70-80% reduction in the ATP/ADP and phosphorylation potential, and a 2.5-fold increase in the NAD/NADH. Associated with these changes was a marked displacement of the phosphoglycerate kinase (PGK), and the combined glyceraldehyde-3-phosphate dehydrogenase-PGK reactions from thermodynamic equilibrium. As a general conclusion, fatigue and exhaustion should be viewed as a multicomponent biochemical process in response to low glycogen and not leveled at one particular step of the glycolytic pathway.
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PMID:Regulation of anaerobic ATP-generating pathways in trout fast-twitch skeletal muscle. 360 83

Subjects maintained an isometric contraction of the quadriceps femoris muscle at two-thirds maximal voluntary contraction (m.v.c.) force for 5 s (5.0 +/- 0.3 s; mean +/- S.E. of mean; n = 6) or until fatigue (52 +/- 4 s; n = 13). Muscle biopsies were obtained at rest, immediately after the contractions and also at 1 and 4 min of recovery after contraction to fatigue. In all subjects 5 s isometric contraction resulted in an increase of muscle NADH (0.084 +/- 0.012 at rest to 0.203 +/- 0.041 mmol/kg dry wt.) and a decrease of phosphocreatine (PC; change in concentration = -17.3 +/- 3.8 mmol/kg dry wt.). Glucose-6-phosphate concentration was more than doubled whereas lactate increased in only four of the six subjects. The two subjects who did not show any increase in lactate also had the lowest increase in NADH. At fatigue NADH increased to 0.226 +/- 0.032 mmol/kg dry wt. which was not significantly different from the value after 5 s contraction. Muscle PC was nearly depleted and lactate increased 12-fold above resting levels. The major part (65%) of the NADH increase at fatigue had reverted after 1 min recovery but only a slight further decrease occurred between 1 and 4 min of recovery. In relative terms the time course of the changes in muscle NADH during the first minute of recovery was similar to that of PC resynthesis, suggesting a common regulator such as O2 availability. In contrast to the delayed return of NADH concentration, PC resynthesis continued during the later part of the recovery period and PC concentration was almost fully restored after 4 min of recovery. It is concluded that muscle NADH is already maximally increased in the first seconds of muscle contraction at two-thirds m.v.c. Indirect evidence indicates that this increase reflects a reduction of the mitochondrial NAD-NADH redox couple. The rapid establishment of a reduced mitochondrial redox state at the start of muscle contraction will probably lead to a reduction of the redox state in the cytoplasm also and therefore be important for enhancing lactate formation.
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PMID:Redox state changes in human skeletal muscle after isometric contraction. 361 70

Mitochondrial myopathies are a clinical condition characterized by muscle weakness and fatigue in which the primary defect is localized at the level of the mitochondria. Microscopic examination shows accumulations of mitochondria at the fibre periphery (ragged red fibres) and in some cases mitochondrial paracrystalline inclusions. The spectrum of different mitochondrial defects so far described is reviewed and data from cases investigated in this laboratory are described. The first case was a 17-year-old boy with a multisystem disorder whose muscle mitochondria showed low respiratory activity with all substrates, which doubled in the presence of uncoupler. Further investigation showed that the mitochondrial ATPase activity was only 6% of normal. The next cases were a mother and daughter who showed a typical lipid storage myopathy. The latter was treated successfully with oral carnitine but the myopathy persisted. Mitochondrial investigations indicated a low respiratory activity with NAD-linked substrates but normal activity with succinate and ascorbate + TMPD. A defect in the NADH-CoQ reductase section of the respiratory chain was pinpointed possibly at an iron-sulphur centre. The fourth and fifth cases were two sisters who exhibited no lipid storage myopathy but whose mitochondrial activity was low with NAD-linked substrates but normal with succinate. Again a defect in the NADH-CoQ reductase (complex I) of the respiratory chain was determined. They were also investigated using 31P-NMR. It was found after exercise that their muscle creatine phosphate levels took seven times longer to return to pre-exercise concentrations than control subjects. These results are discussed with respect to the synthesis of mitochondrial proteins and the influence that both the mitochondrial and nuclear DNA have on this process.
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PMID:Mitochondrial myopathies: disorders of the respiratory chain and oxidative phosphorylation. 643 47


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