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

The pathophysiology of the myopathy in dysthyroid states is poorly understood. We therefore tested the effects of thyroid hormones on muscle bioenergetics in humans and rats, using in vivo 31P NMR. Two hypothyroid patients had: low phosphocreatine to inorganic phosphate ratio (PCr/Pi) at rest, increased PCr depletion during exercise and delayed postexercise recovery of PCr/Pi. Eight thyroidectomized rats did not show abnormalities at rest, but muscle work induced by nerve stimulation resulted in a significantly (P less than 0.0001) lower PCr/Pi (35-45% of control) at each of the three stimulation frequencies tested (0.25, 0.5, and 1.0 Hz). Recovery rate was markedly slowed to one-third of normal values. Thyroxine therapy reversed these abnormalities in both human and rat muscle. Five patients and six rats with hyperthyroidism did not differ from normal controls during rest and exercise but had an unusually rapid recovery after exercise. The bioenergetic abnormalities in hypothyroid muscle suggest the existence of a hormone-dependent, reversible mitochondrial impairment in this disorder. The exercise intolerance and fatigue experienced in hypothyroid muscle may be due to such a bioenergetic impairment. The changes in energy metabolism in hyperthyroid muscle probably do not cause the muscular disease in this disorder.
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PMID:Effects of thyroid hormones on skeletal muscle bioenergetics. In vivo phosphorus-31 magnetic resonance spectroscopy study of humans and rats. 338 46

Magnetic resonance spectroscopy is a non-invasive and repeatable method of studying muscle metabolism. Magnetic resonance spectroscopy uses specific radiofrequency pulses in a strong magnetic field to determine the relative concentrations of chemical compounds in the sample. 31P Magnetic resonance spectroscopy provides indirect measures of phosphate compounds such as adenosine triphosphate (ATP), phosphocreatine and inorganic phosphate. Muscle intracellular pH can also be determined. Exercise tests can be performed in the magnet such that the metabolic response to steady-state exercise can be measured. The ratio of inorganic phosphate to phosphocreatine reflects the relative metabolic rate of mitochondrial respiration (V) and the extrapolated maximum capacity of oxidative metabolism (Vm). Normal humans vary considerably in their metabolic response to exercise. These differences are reflected in their Vms and the degree of acidosis during exercise. Active muscles in endurance trained athletes have higher Vms and faster recovery rates than normal controls. Preliminary studies have been done to assess muscle glycolytic capacity by measuring the degree of acidosis during ischaemic exercise. Exercise-induced muscle injury can be detected as an increased inorganic phosphate to phosphocreatine ratio in resting muscle. The increase in the inorganic phosphate to phosphocreatine ratio with injury reaches a peak 1 to 2 days after the injury and lasts for up to a week. Similar increases in the inorganic phosphate to phosphocreatine ratio occur in patients with destructive neuromuscular diseases. Thus changes in the resting inorganic phosphate to phosphocreatine ratio may be used to detect the degree of muscle injury following exercise. Levels of H2PO4- in muscle are thought to be important in causing muscle fatigue during exercise. As 31P magnetic resonance spectroscopy can measure H2PO4-, magnetic resonance spectroscopy has become a useful technique in the study of the metabolic causes of muscle fatigue. It may also be possible to identify the relative populations of fast twitch and slow twitch fibres in a skeletal muscle using pH changes measured with 31P magnetic resonance spectroscopy. Magnetic resonance spectroscopy using other nuclei, such as 1H, 13C and 23Na, have the potential to provide information on other metabolic changes which occur with exercise. Magnetic resonance spectroscopy has shown promise as a technique to monitor the effects of training, including overtraining, in specific muscle groups in athletes.
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PMID:Application of 31P magnetic resonance spectroscopy to the study of athletic performance. 338 35

The effects of the vasodilating dihydropyridine, felodipine, on tissue concentrations of high-energy phosphates and on oxygen consumption and lactate production in the smooth muscle of the rat portal vein were investigated. Felodipine (100 nM) caused a gradual decrease in the amplitude of the spontaneous phasic contractions in a calcium-containing medium. The mean active force was reduced by about 80% within 15 min. The inhibition of force was associated with reductions in both oxygen consumption and lactate production. No effects of felodipine could be observed in a calcium-free solution. The metabolic rates and force during felodipine inhibition approached those recorded in the calcium-free media. Felodipine (30 nM) did not alter the tissue levels of ATP, ADP, AMP and phosphocreatine. Relaxation by felodipine is thus associated with a decreased energy demand for contraction and, possibly, ionic translocation. The reduced ATP hydrolysis is compensated for by the regeneration of metabolic ATP, thus keeping the cellular levels of high-energy phosphates constant.
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PMID:Effects of felodipine on energy turnover in the rat portal vein. 340 35

The content of glucose 1,6-bisphosphate (G-1,6-P2), an in vitro activator of phosphofructokinase (a rate-limiting enzyme for glycolysis), and the glycolytic rate in skeletal muscle during isometric contraction have been determined. Subjects contracted the knee extensor muscles at two-thirds maximal voluntary force to fatigue. Biopsies from the quadriceps femoris muscle were obtained before and immediately after contraction. G-1,6-P2 increased in all subjects from a mean of 101 +/- 15 (SE) mumol/kg dry wt at rest to 128 +/- 24 at fatigue (P less than 0.05). Muscle glucose did not change significantly, whereas hexosemonophosphates were significantly increased after contraction. The glycogenolytic and glycolytic rate averaged 70.0 +/- 13.8 and 47.3 +/- 6.7 mmol.kg dry wt-1.min-1, respectively, and the glycolytic rate was positively correlated with the accumulation rates of fructose 6-phosphate (F-6-P) (r = 0.95, P less than 0.01) and G-6-P (r = 0.96, P less than 0.01). Phosphocreatine and ATP decreased by 87 and 17%, respectively, whereas ADP increased by 31% after contraction. These data demonstrate that intense, short-term isometric contraction results in an elevation of the muscle content of G-1,6-P2. The increase in G-1,6-P2 could not be accounted for by the side reactions of phosphoglucomutase or phosphofructokinase. It remains to be determined whether the observed increase in G-1,6-P2 is sufficient to account for the high glycolytic rate during intense exercise. The lack of increase in muscle glucose while G-6-P increased (which will inhibit hexokinase) suggests that the debranching enzyme complex was not active during contraction.
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PMID:G-1,6-P2 in human skeletal muscle after isometric contraction. 340 60

Six male subjects performed intensive cycle exercise to exhaustion after cooling their legs in water at 10-12 degrees C (muscle temperature (Tm) 28 +/- 2.6 degrees C, mean +/- SD). Exercise at exactly the same rate and duration (370 +/- 34 W, 1.5 +/- 0.2 min) was then repeated by each subject 2-5 weeks later at normal Tm (35 +/- 1.0 degrees C). Muscle biopsies were taken from the vastus lateralis muscle at rest and after exercise. The muscle tissue was freeze-dried and fragments of single fibres were dissected out. The fibres were classified and pooled into groups of type I and type II. Analyses of glycogen, glucose 6-phosphate, lactate and phosphagens were performed on pools of type-identified fibres. After exercise at reduced Tm, all subjects had higher concentrations of glucose 6-phosphate and lactate in both type I and type II fibres, and in most subjects the concentrations of ATP and phosphocreatine were lower as compared with the findings after exercise at normal Tm. During exercise the glycogen content of both fibre types decreased to a greater extent at reduced than at normal Tm in most subjects. The results suggest that during intensive dynamic exercise at reduced Tm there is a higher degree of glycolysis from glycogen in the muscle than in the normal situation. In some subjects the cause of fatigue may be related to a more rapid accumulation of lactate in the cold muscle, while in others fatigue may be related to alternative factors, e.g. low levels of ATP and phosphocreatine.
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PMID:Influence of reduced muscle temperature on metabolism in type I and type II human muscle fibres during intensive exercise. 344 42

Experiments are described which suggest that the loss of force generating capacity seen during fatigue from intermittent, submaximal voluntary contractions of the quadriceps muscle cannot be explained by any of the usual factors thought to be responsible for fatigue. During the first 30 min of intermittent contractions at 30% MVC the force generated periodically by a brief test train of 50 Hz stimulation and by brief maximal voluntary contractions both declined by 50%. Yet no significant changes were seen in the muscle lactate, ATP or phosphocreatine. Glycogen depletion was confined only to the type I and type IIA fibres, with less than 10% totally depleted. The depletion patterns indicated that the type IIAB and type IIB motor units were not recruited during the first 30 min. The central nervous system appeared to remain capable of generating full muscle activation since the force from maximal voluntary efforts declined in parallel with that from 50 Hz stimulation. We suggest that, in this type of fatigue, the loss of force may be largely due to impaired excitation/contraction coupling. This possibility is supported by the disproportionate depression of the twitches recorded between contractions compared with that from 50 Hz stimulation (low frequency fatigue). The single unit EMG recordings suggest that, in sustained and repeated submaximal contractions, muscle contractile failure is compensated by recruitment of additional motor units rather than by rate coding of those already active. During intermittent contractions large increases in the surface EMG were associated with only modest increases in firing rates. In sustained contractions when the EMG was held constant the discharge rates declined in parallel with the force. In constant force contractions involving about 35% muscle contractile failure no changes in discharge rates were seen despite substantial increases in EMG.
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PMID:Fatigue of submaximal static contractions. 347 Oct 51

Isolated soleus muscle of rat was stimulated electrically (2 Hz) for 7 min under anaerobic conditions. Isometric twitch tension decreased progressively and was 30% of the initial value at the end of stimulation. The decline in relative force was similar to that previously observed in fast twitch muscle and soleus can thus not be termed fatigue-resistant under anaerobic conditions. Phosphocreatine (PCr) decreased from (mean +/- SD) 61.1 +/- 4.4 at rest to 4.0 +/- 1.8 mmol kg-1 dry muscle (d.m.) after 7 min of stimulation, while lactate increased from 3.7 +/- 1.6 to 30 +/- 8 mmol kg-1 d.m. Energy was thus derived from complete utilization of PCr and a low rate of glycolysis resulting in an almost unchanged calculated intracellular pH. It is concluded that tension decline in soleus muscle is not due to decreased intracellular pH but is more related to the capacity to regenerate ATP at a sufficient rate. Contraction and relaxation time of the twitch remained practically constant during the stimulation period. In contrast prolonged activation of fast-twitch muscle results in a slowing of the relaxation of the twitch (Sahlin et al. 1981) and it has been suggested that this is caused by the decrease of intracellular pH. The constancy of both relaxation time and calculated pH in the fatigued soleus muscle is consistent with the hypothesis that there is a connection between these two parameters. In contrast to the twitch, relaxation of tension after a tetanus was prolonged in soleus. Hence, it appears that the rate limiting step for relaxation is different for a twitch than for a tetanus in soleus.
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PMID:Force, relaxation and energy metabolism of rat soleus muscle during anaerobic contraction. 356 37

This study examined the effect of high- (75 Hz, 1 min) and low- (5 Hz, 1.5 min) frequency stimulation on contractile and biochemical properties of the diaphragm. Tension was reduced to 21 +/- 1 and 54 +/- 2% (SE) of the initial value after high- and low-frequency stimulation, respectively. After 0, 0.25, 1, and 2 min of recovery from high-frequency stimulation, 5 Hz elicited more force (expressed as % of initial tension) than 75-Hz stimulation. Time 0 recovery values were 21 +/- 1 and 78 +/- 6% of the initial force for 75- and 5-Hz stimulation, respectively. By 1 min of recovery, force elicited by 5-Hz stimulation had returned to the prefatigue value. In contrast, force production with 75-Hz stimulation did not full recover until 10-15 min. After fatigue produced by low-frequency stimulation, force production with 5-Hz stimulation was reduced to 54 +/- 2% of the initial tension, a value significantly lower than the 71 +/- 2% of initial force elicited by 75-Hz stimulation. Force production with 5-Hz stimulation increased rapidly in the first 15 s of recovery (54 +/- 2% at 0 and 70 +/- 2% at 15 s) and by 5 min was significantly greater than the force elicited by 75-Hz stimulation (100 +/- 3 vs. 93 +/- 1%). As before, force production at 75-Hz stimulation did not fully recover until 10-15 min. Both fatigue protocols produced a significant prolongation in isometric twitch contraction and one-half relaxation times. Creatine phosphate (CP) concentration was reduced and muscle lactate increased by both fatigue protocols.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fatigue from high- and low-frequency muscle stimulation: contractile and biochemical alterations. 359 76

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


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