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

In a single-blind trial 25 patients with progressive scleroderma and Raynaud's phenomenon intravenous infusions of iloprost, a prostacyclin derivative (carbaprostacyclin), were given daily for five hours during a six-day hospital stay, after a comparable initial single placebo infusion. Duration, frequency and intensity of Raynaud symptoms improved in more than 75% of the patients. This improvement was objectified by telethermometry which demonstrated acral hyperthermia and significantly briefer rewarming after standardized cooling of the hands. In addition, there was more rapid healing of ulcerations and necroses of the digital pulp. A significant inhibition of ADP- and collagen-dependent platelet aggregation was demonstrated during the iloprost infusion. Side effects, such as headache, nausea and tiredness occurred only transitorily during the infusion, were individually highly variable, and then only at higher concentrations. A dosage of 2 ng/kg X min was tolerated by all patients.
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PMID:[Treatment of Raynaud's phenomenon in scleroderma with a new stable prostacyclin derivative]. 638 60

Isolated extensor digitorum longus muscles from rat were exposed to atmospheres of 30% CO2 (high-CO2 muscles) or 6.5% CO2 (control muscles) in O2 for 95 min. Muscle contraction characteristics were studied before and after the incubation. Tetanic tension decreased in high-CO2 muscles to 55% of initial value but remained unchanged in control muscles. Relaxation time was prolonged in high-CO2 muscles but not in control muscles. Intracellular pH was 6.67 +/- 0.04 (SD) in high-CO2 muscles and 7.01 +/- 0.04 in control muscles. CO2-induced acidosis had a marked influence on the intermediary energy metabolism as shown by a fourfold increase of glucose 6-phosphate, a 14% increase of ADP, and a decrease of phosphocreatine to 44% of the control value. Lactate and pyruvate contents were unchanged. The observed metabolic changes can be explained by an effect of H+ on the activity of phosphofructokinase and on the creatine kinase equilibrium. It can be concluded that H+ concentration causes muscular fatigue. It is, however, uncertain whether this is an effect of increased H+ per se or by high-energy phosphate depletion induced by acidosis.
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PMID:Fatigue and phosphocreatine depletion during carbon dioxide-induced acidosis in rat muscle. 640 27

Uremia is associated with decreased brain oxygen consumption in humans and with decreased brain energy consumption in rodent models of acute renal failure. We measured the levels of high-energy phosphates and glycolytic intermediates in the brain of dogs with acute or chronic renal failure. We used methods of rapid brain tissue fixation that trap these labile metabolites at their in vivo levels. Creatine phosphate, ATP, and glucose were normal in the brain of animals with renal failure, indicating a normal brain energy reserve. The brain energy charge, which is the fraction of the total adenine nucleotide pool that contains high-energy phosphates, (ATP + 1/2ADP)/(ATP + ADP + AMP), was also normal despite an 8% decrease in the total adenine nucleotide pool. Mild hypoxia failed to alter the level of any of these metabolites. The brain redox state, (NAD+)/(NADH), was normal to high in acute renal failure, suggesting that oxygen supply was not limiting oxygen consumption. In the face of normal brain energy reserves, energy charge, and redox state, the decreased energy consumption of uremic brain probably results from decreased demand rather than limited supply.
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PMID:Uremic encephalopathy: role of brain energy metabolism. 647 28

Hypertensive disease is known to increase the risks in connection with acute changes in blood pressure due to the presence of pronounced structural as well as functional changes in the cardiovascular system. In the present study the metabolic consequences of fixed haemorrhagic hypotension [mean arterial pressure (MAP) 70 and 45 mmHg] were studied in spontaneously hypertensive (SHR) and in normotensive rats (WKY). Blood gases and acid-base balance, blood glucose, liver (ATP, glucose, lactate) and brain (ATP, ADP, AMP, CP, glucose, lactate) metabolites were determined in unbled animals and after 35 min hypotension in bled animals. In the liver haemorrhage to MAP 70 mmHg resulted in a 70% reduction of the ATP content in SHR while that in WKY remained unchanged. At MAP 45 mmHg reduced liver ATP levels (35% reduction) were observed in WKY as well. In the brain metabolic changes indicative of tissue ischaemia (reduced CP, increased AMP and lactate, decreased energy charge potential) were present only in SHR at MAP 45 mmHg. The more pronounced metabolic disturbances in SHR than in WKY indicate that blood loss is more deleterious for the hypertensive individual.
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PMID:Effects of haemorrhagic hypotension on brain and liver metabolism in normotensive (WKY) and spontaneously hypertensive rats (SHR). 668 Oct 40

To assess the role of the purine nucleotide cycle in human skeletal muscle function, we evaluated 10 patients with AMP deaminase deficiency (myoadenylate deaminase deficiency; MDD). 4 MDD and 19 non-MDD controls participated in an exercise protocol. The latter group was composed of a patient cohort (n = 8) exhibiting a constellation of symptoms similar to those of the MDD patients, i.e., postexertional aches, cramps, and pains; as well as a cohort of normal, unconditioned volunteers (n = 11). The individuals with MDD fatigued after performing only 28% as much work as their non-MDD counterparts. Muscle biopsies were obtained from the four MDD patients and the eight non-MDD patients at rest and following exercise to the point of fatigue. Creatine phosphate content fell to a comparable extent in the MDD (69%) and non-MDD (52%) patients at the onset of fatigue. Following exercise the 34% decrease in ATP content of muscle from the non-MDD subjects was significantly greater than the 6% decrease in ATP noted in muscle from the MDD patients (P = 0.048). Only one of four MDD patients had a measurable drop in ATP compared with seven of eight non-MDD patients. At end-exercise the muscle content of inosine 5'-monophosphate (IMP), a product of AMP deaminase, was 13-fold greater in the non-MDD patients than that observed in the MDD group (P = 0.008). Adenosine content of muscle from the MDD patients increased 16-fold following exercise, while there was only a twofold increase in adenosine content of muscle from the non-MDD patients (P = 0.028). Those non-MDD patients in whom the decrease in ATP content following exercise was measurable exhibited a stoichiometric increase in IMP, and total purine content of the muscle did not change significantly. The one MDD patient in whom the decrease in ATP was measurable, did not exhibit a stoichiometric increase in IMP. Although the adenosine content increased 13-fold in this patient, only 48% of the ATP catabolized could be accounted for by the combined increases of adenosine, inosine, hypoxanthine, and IMP. Studies performed in vitro with muscle samples from seven MDD and seven non-MDD subjects demonstrated that ATP catabolism was associated with a fivefold greater increase in IMP in non-MDD muscle. There were significant increases in AMP and ADP content of the muscle from MDD patients following ATP catabolism in vitro, while there was no detectable increase in AMP or ADP in non-MDD muscle. Adenosine content of MDD muscle increased following ATP catabolism, but there was no detectable increase in adenosine content of non-MDD muscle following ATP catabolism in vitro. These studies demonstrate that AMP deaminase deficiency leads to reduced entry of adenine nucleotides into the purine nucleotide cycle during exercise. We postulate that the resultant disruption of the purine nucleotide cycle accounts for the muscle dysfunction observed in these patients.
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PMID:Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle. 670 1

Previous observations have shown that in human subjects with malnutrition and after prolonged fasting, there are characteristic changes in the force-frequency response, relaxation rate and power of muscle during a 30 s stimulus (fatigue). In order to characterize these findings under carefully controlled conditions, in different types of muscle and to correlate them with changes in muscle structure, composition and biochemical status, we developed an animal model in rats. In this model, nutrient restriction, both after an acute fast and after chronic hypocaloric feeding, resulted in: (a) loss of force during high frequency stimulation but preservation of contraction-relaxation characteristics during low frequency stimulation; (b) slower muscle relaxation rate at high frequency stimulation; (c) increased muscle fatiguability at high frequency stimulation. Measurements of muscle enzymes showed that acute fasting resulted in a reduced content of glycolytic enzymes, but preservation of oxidative enzymes, while chronic hypocaloric dieting resulted in a reduction in both classes of enzyme. There was no significant change in ATP, AMP or energy charge, or in intracellular sodium, potassium and magnesium levels. Creatine phosphate was normal in acutely fasted animals but low in those fed hypocalorically. By contrast, increased intracellular calcium and ADP levels were seen in both fasted and hypocalorically fed animals. These findings suggest that subtle disturbances of intracellular energy states with altered calcium flux may be of importance in the genesis of muscle dysfunction caused by malnutrition.
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PMID:The effect of fasting and hypocaloric diets on the functional and metabolic characteristics of rat gastrocnemius muscle. 674 88

The technique of nuclear magnetic resonance (n.m.r.) is briefly described to illustrate its use for estimating metabolite levels in vivo. Our studies of fatigue in anaerobic frog muscle at 4 degree C are described in relation to (a) force development, (b) speed of relaxation and (c) the switching on and off of glycolysis. Both (a) and (b) are closely related, though in different ways, to the concentrations of key metabolites. In contrast, (c) is not related to metabolite levels as such but to the events of contraction and relaxation. A special n.m.r. technique (saturation transfer) has been used to study the creatine kinase system in vivo. The results show that this system is highly active and is in equilibrium in resting muscle. The free [ADP] is consequently only a small fraction of that found by analysis of muscle extracts. Studies of human power production as a function of duration of exercise also indicate that it is shortage of chemical fuel that brings short- and medium-term exercise (0.1-10 min) to a halt. It is proposed to extend n.m.r. methods to human subjects in the near future. A working hypothesis to account for fatigue is suggested in which both the contractile system and the activating system play a part.
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PMID:Shortage of chemical fuel as a cause of fatigue: studies by nuclear magnetic resonance and bicycle ergometry. 691 67

During vigorous, strong contractions there is a rapid decline in the mechanical output or tension development in skeletal muscle. Several studies have indicated that this rapid decline in force development (often referred to as fatigue), is caused by metabolic changes in the muscles. During brief intense exercise there is a rapid breakdown of phosphocreatine and glycogen and a concomitant increase in the lactate and hydrogen ion concentration. The muscle lactate concentration is increased from about 1-2 mmol kg-1 wet weight at rest before exercise to approximately 25-30 mmol kg-1 wet weight immediately after intensive brief exercise to exhaustion. The muscle pH (i.e. the pH of muscle homogenates) falls from about 7.0 at rest to approximately 6.4 at exhaustion. The changes in the concentrations of ATP, ADP, and AMP are small. It is suggested that the changes in intracellular pH might affect the force generation of skeletal muscle by two different mechanisms: (1) The fall in intracellular pH reduces the activity of key enzymes in glycolysis, thus reducing the rate of ATP resynthesis, and (2) the increased hydrogen ion concentration has a direct effect on the contractile processes, thus reducing the rate of ATP utilization. It is suggested that the increased hydrogen ion concentration might be the common regulator for the maximal rate at which ATP is being utilized and the maximal rate at which it is being resynthesized.
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PMID:Effect of metabolic changes on force generation in skeletal muscle during maximal exercise. 691 79

1. We have used phosphorus nuclear magnetic resonance (31P NMR) to study muscular fatigue in anaerobic amphibian muscle. In this paper the biochemical and energetic changes that result from a series of tetani are related to the decrease in rate constant (1/tau) for the final, exponential, phase of relaxation. 2. Using 31P NMR we have measured the concentrations of phosphocreatine (PCr), inorganic phosphate (Pi) and ATP as well as the internal pH. From our measurements we have calculated [creatine], [free ADP], the free-energy change (more precisely, the affinity A = -dG/d xi) for ATP hydrolysis and the rates of lactic acid production and of ATP hydrolysis. 3. We have found that 1/tau, the rate constant of relaxation, is correlated with each of the following, independently of the pattern of stimulation: isometric force production, all of the measured or calculated metabolite levels, pH and dG/d xi. 4. There is a clear dependence upon the pattern of stimulation of the relation between 1/tau and each of the following: total duration of the experiment, number of contractions, rate of lactic acid production and rate of ATP hydrolysis. 5. The rate of relaxation is linearly related to [PCr], [creatine], [Pi] and dG/d xi. It is nonlinearly related to isometric force, [ATP], [H+] and rate of ATP hydrolysis. 6. We conclude that the change in 1/tau, like that of isometric force, depends upon metabolic factors, and not upon any independent changes in the activation or deactivation of contraction. We suggest that 1/tau may depend upon the free-energy change for ATP hydrolysis which in turn may be related to the rate of Ca2+ uptake into the sarcoplasmic reticulum.
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PMID:Mechanical relaxation rate and metabolism studied in fatiguing muscle by phosphorus nuclear magnetic resonance. 696 88

1 (+)-Octanoylcarnitine, a potent inhibitor of fatty acid oxidation, was infused intraportally into rabbits after 70% hepatectomy, and its effects on the rate of deoxyribonucleic acid (DNA) synthesis were examined. 2. The rate of DNA synthesis was markedly enhanced 48 h after hepatectomy. At this time, synthesis was decreased significantly by (+)-octanoylcarnitine. 3. It is suggested that fatty acid oxidation contributes to enhanced hepatic regeneration by elevating the decreased energy charge level [(ATP + 0.5ADP)/(ATP + ADP + AMP)] of the remnant liver.
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PMID:Effects of (+)-octanoylcarnitine on deoxyribonucleic acid synthesis in regenerating rabbit liver. 706 Mar 36


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