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

31P NMR spectroscopy was used to study the energy metabolism of dystrophin-deficient skeletal muscle of mdx mice, an animal model of Duchenne muscular dystrophy, in which expression of a truncated form of utrophin has been obtained through transgenesis technology. Measurements of ATP, phosphocreatine (PCr), inorganic phosphates (Pi) and intracellular pH (pHi) were made at rest, during a fatigue protocol and during the subsequent recovery. Mechanical fatigue of transgenic muscles was similar to normal muscle, while mdx muscle showed larger force loss. At rest, muscles of all groups had similar values for [ATP], [PCr], [Pi] and pHi. During fatigue, [PCr] decreases mirrored [Pi] increases and were similar in all groups. The major difference between mdx muscles and the group of normal and trc-utrophin muscles concerned the values and evolution of pHi. The mdx muscles showed a more severe intracellular acidosis during exercise and a slower and incomplete post-exercise recovery of normal pHi. In contrast, in trc-utrophin muscles, the kinetics and amplitude of pHi changes were remarkably close to normal behaviour. We conclude that the impaired proton washout which is present in mdx muscles, is corrected to a great extent by the expression of trc-utrophin.
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PMID:Expression of truncated utrophin improves pH recovery in exercising muscles of dystrophic mdx mice: a 31P NMR study. 971 53

Increases in skeletal muscle (1)H-NMR transverse relaxation time (T2) observed by magnetic resonance imaging have been used to map whole muscle activity during exercise. Some studies further suggest that intramuscular variations in T2 after exercise can be used to map activity on a pixel-by-pixel basis by defining an active T2 threshold and counting pixels that exceed the threshold as "active muscle." This implies that motor units are nonrandomly distributed across the muscle and, therefore, that the distribution of pixel T2 values ought to be substantially broader after moderate exercise than at rest or after more intense exercise, since moderate-intensity exercise should recruit some motor units, and hence some pixels, but not others. This study examined the distribution of pixel T2 values in three muscles (quadriceps, anterior tibialis, and biceps/brachialis) of healthy subjects (5 men and 2 women, 18-46 yr old) at rest, after exercise to fatigue (50% 1 repetition maximum at 20/min to failure = Max), and at 1/2Max (25% 1 repetition maximum, same number of repetitions as Max). Although for each muscle there was a linear relationship between exercise intensity and mean pixel T2, there was no significant difference in the variance of pixel T2 between 1/2Max and Max exercise. There was a modest (10-43%) increase in variance of pixel T2 after both exercises compared with rest, but this was consistent with a Monte Carlo simulation of muscle activity that assumed a random distribution of motor unit territories across the muscle and a random distribution of muscle cells within each motor unit's territory. In addition, 40% of the pixel-to-pixel muscle T2 variations were shown to be due to imaging noise. The results indicate that magnetic resonance imaging T2 cannot reliably map active muscle on a pixel-by-pixel basis in normal subjects.
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PMID:Pixel T2 distribution in functional magnetic resonance images of muscle. 1060 Nov 56

Six healthy subjects rapidly lifted and lowered a small (250 g) weight with the first dorsal interosseous muscle (FDI) of one hand while the work performed was recorded continuously until fatigue (defined as losing the ability to continue lifting). Work was recorded in units of chart recorder trace displacement from baseline (centimeters) as an isotonic transducer followed the movement of the weight. In all experiments, the temperature of the hand was first adjusted by immersion in a controlled-temperature water bath. In the warmest condition, the skin surface temperature over the FDI was 30.5(0.30) degrees C [mean (SE)]. After moderate cooling, this surface temperature was 21.5(0.16) degrees C. Cooling significantly reduced the time taken to reach fatigue and more than halved the work capacity. An intermediate degree of cooling was also used in four subjects, showing that most of the effects seen were changing incrementally. Before work, and at fatigue, intracellular metabolic conditions in the FDI were studied by phosphorus nuclear magnetic resonance (31P-NMR) spectroscopy, with occlusion of the blood flow maintained during measurements. The mean intracellular pH of the FDI was also calculated. The changes observed were all consistent with the fact that intense work requires energy which must be derived largely from intracellular stores of phosphocreatine and glycogen. Less work made less demand upon reserves, and created lower concentrations of waste products and by-products. The observations did not, however, allow us to explain why fatigue occurred at a particular point or why work capacity was reduced by cooling.
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PMID:Influence of muscle temperature during fatiguing work with the first dorsal interosseous muscle in man: a 31P-NMR spectroscopy study. 1063 78

To assess effects of smooth muscle energy state and intracellular pH (pH(i)) on pulmonary arterial tone during hypoxia, we measured ATP, phosphocreatine, P(i), and pH(i) by (31)P-NMR spectroscopy and isometric tension in phenylephrine-contracted rings of porcine proximal intrapulmonary arteries. Hypoxia caused early transient contraction followed by relaxation and late sustained contraction. Energy state and pH(i) decreased during relaxation and recovered toward control values during late contraction. Femoral arterial rings had higher energy state and lower pH(i) under baseline conditions and did not exhibit late contraction or recovery of energy state and pH(i) during hypoxia. In pulmonary arteries, glucose-free conditions abolished late hypoxic contraction and recovery of energy state and pH(i), but endothelial denudation abolished only late hypoxic contraction. NaCN had little effect at 0. 1 and 1.0 mM but caused marked vasorelaxation and decreases in energy state and pH(i) at 10 mM. These results suggest that 1) regulation of tone, energy state, and pH(i) differed markedly in pulmonary and femoral arterial smooth muscle, 2) hypoxic relaxation was mediated by decreased energy state or pH(i) due to hypoxic inhibition of oxidative phosphorylation, 3) recovery of energy state and pH(i) in hypoxic pulmonary arteries was due to accelerated glycolysis mediated by mechanisms intrinsic to smooth muscle, and 4) late hypoxic contraction in pulmonary arteries was mediated by endothelial factors that required hypoxic recovery of energy state and pH(i) for transduction in smooth muscle or extracellular glucose for production and release by endothelium.
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PMID:Energy state, pH, and vasomotor tone during hypoxia in precontracted pulmonary and femoral arteries. 1066 13

In exercising muscle, interstitial metabolites accumulate and stimulate muscle afferents. This evokes the muscle metaboreflex and raises arterial blood pressure (BP). In this report, we examined the effects of tension generation on muscle metabolites and BP during ischemic forearm exercise in humans. Heart rate (HR), BP, P(i), H(2)PO(4)(-), and pH ((31)P-NMR spectroscopy) data were collected in 10 normal healthy men (age 23 +/- 1 yr) during rhythmic handgrip exercise. After baseline measurements, the subjects performed rhythmic handgrip for 2 min. At 2 min, a 250-mmHg occlusion cuff was inflated, and ischemic handgrip exercise was continued until near fatigue (Borg 19). Measurements were continued for an additional 30 s of ischemia. This protocol was performed at 15, 30, 45, and 60% of the subjects' maximum voluntary contraction (MVC) in random order. As tension increased, the time to fatigue decreased. In addition, mean arterial pressure and HR were higher at 60% MVC than at any of the other lower tensions. The NMR data showed significantly greater increases in H(2)PO(4)(-), P(i), and H(+) at 60% than at 15 and 30% MVC. Therefore, despite the subjects working to the same perceived effort level, a greater reflex response (represented by BP and HR data) was elicited at 60% MVC than at any of the other ischemic tensions. These data are consistent with the hypothesis that, as tension increases, factors aside from insufficient blood flow contribute to the work effect on muscle metabolites and the magnitude of the reflex response.
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PMID:Ischemic exercise and the muscle metaboreflex. 1100 79

Stimulated by recent (13)C and (31)P NMR studies of exercising muscle, we propose a model of the energetics of contraction. Previous studies of energetics have followed energy consumption. However, the rapidity of contraction, in 10-40 msec, requires that energy be delivered rapidly, so that the muscle has power requirements of rapid energy expenditure that are ultimately met by the slower averaged consumption of carbon and oxygen from blood. We propose that energy is supplied in milliseconds by glycogenolysis and that between contractions, glycogenesis refills the pools. The energy for glycogenesis is supplied by oxidative phosphorylation. This mechanism utilizes the rapid conversion of glycogen phosphorylase, the "fight-or-flight" enzyme, to its active form. Lactate is necessarily generated by this pathway to serve as a time buffer between fast and slow energy needs, which resolves the paradoxical generation of lactate in well oxygenated tissue. Consequences of the glycogen shunt are compatible with numerous biochemical and physiological experiments. The model provides a possible mechanism for muscle fatigue, suggesting that at low but nonzero glycogen concentrations, there is not enough glycogen to supply millisecond energy needs.
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PMID:The "glycogen shunt" in exercising muscle: A role for glycogen in muscle energetics and fatigue. 1120 49

Dimethylglycine dehydrogenase (DMGDH) (E.C. number 1.5.99.2) is a mitochondrial matrix enzyme involved in the metabolism of choline, converting dimethylglycine to sarcosine. Sarcosine is then transformed to glycine by sarcosine dehydrogenase (E.C. number 1.5.99.1). Both enzymes use flavin adenine dinucleotide and folate in their reaction mechanisms. We have identified a 38-year-old man who has a lifelong condition of fishlike body odor and chronic muscle fatigue, accompanied by elevated levels of the muscle form of creatine kinase in serum. Biochemical analysis of the patient's serum and urine, using (1)H-nuclear magnetic resonance NMR spectroscopy, revealed that his levels of dimethylglycine were much higher than control values. The cDNA and the genomic DNA for human DMGDH (hDMGDH) were then cloned, and a homozygous A-->G substitution (326 A-->G) was identified in both the cDNA and genomic DNA of the patient. This mutation changes a His to an Arg (H109R). Expression analysis of the mutant cDNA indicates that this mutation inactivates the enzyme. We therefore confirm that the patient described here represents the first reported case of a new inborn error of metabolism, DMGDH deficiency.
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PMID:Cloning of dimethylglycine dehydrogenase and a new human inborn error of metabolism, dimethylglycine dehydrogenase deficiency. 1123 3

The aim of this study was to examine the effect of the products of ATP hydrolysis on the fatigue process in rat gastrocnemius in vivo. Adult male Sprague-Dawley rats (300-400 g) were anesthetized and ventilated in a custom-built cradle fitted with a force transducer that could be placed into a 7-T NMR magnet. The muscle was stimulated continuously at 2 Hz for 20 min (n = 7). Isometric twitch force increased in the first 4 min of stimulation accompanied by changes in twitch duration (20% increase in relaxation time). Prolonged relaxation was associated with changes in cytosolic pH (6.91 to 6.58), lactate (1.8 to 12.6 micromol/g wet wt), and H(2)PO (7.57 to 13.99 mM). After 4 min, relaxation time, pH, lactate, and H(2)PO returned toward control values as twitch force progressively decreased. No correlation was found between force decline (or twitch broadening) and total phosphate (3 to 23 mM), free [ADP] (18 to 95 microM), free [Mg(2+)] (0.58 to 0.96 mM), or free energy of ATP hydrolysis (-65 to -55 kJ/mol). We conclude that force decline is not due to increased pH and/or H(2)PO but to fatigue of the fast-twitch fibers, possibly linked to glycogen depletion and/or failure of nerve impulse transmission in these fibers.
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PMID:Force reduction uncoupled from pH and H(2)PO(-)(4) in rat gastrocnemius in vivo with continuous 2-Hz stimulation. 1144 55

Although the ultimate cause for the myocardial dysfunction of hypertensive heart disease is still unclear, a crucial role of the myocardial energy metabolism has been suggested. Therefore, the aim of the present study was to investigate whether age-related myocardial dysfunction in hearts of spontaneously hypertensive rats (SHR) is associated with an impaired myocardial energy metabolism. Isolated hearts of SHR and Wistar Kyoto rats (WKY) aged about 40, 60, and 80 weeks, respectively (each n = 4-5), were perfused according to the working heart technique. Cardiac work and coronary flow were monitored online. Myocardial energy metabolism was evaluated by calculating the ratio of phosphocreatine (PCr) and adenosine triphosphate (ATP) which were measured by nuclear magnetic resonance (31P-NMR) spectroscopy. All hearts were subjected to work for 30min at baseline conditions (low afterload), followed by another 30min under a moderate pressure load (high afterload). Each SHR group showed a higher heart weight/body weight ratio than the age-matched WKY controls. The SHR showed a progressive age-dependent reduction of cardiac work (40 weeks = 5.1+/-0.3, 60 weeks = 4.0+/-0.3, 80 weeks = 3.8+/-0.2 (mW/g) at baseline conditions) and PCr/ATP-ratio (40 weeks = 1.82+/-0.06, 60 weeks = 1.69+/-0.05, 80 weeks = 1.59+/-0.09 (PCr/ATP) at baseline conditions). Similar results were found for hearts of SHR at high afterload. In WKY no significant decline in cardiac work or PCr/ATP-ratio was found under either low or under high afterload. The cardiac work capacity of hearts of SHR progressively decreases with increasing age and left ventricular hypertrophy. This myocardial dysfunction is closely associated with an impaired PCr/ATP-ratio, suggesting a decreased energy reserve.
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PMID:Age-related decline of PCr/ATP-ratio in progressively hypertrophied hearts of spontaneously hypertensive rats. 1147 60

Increasing stimulation frequency has been shown to increase fatigue but not when the changes in force associated with changes in frequency have been controlled. An effect of frequency, independent of force, may be associated with the metabolic cost resulting from the additional activations. Here, two separate experiments were performed on human medial gastrocnemius muscles. The first experiment (n = 8) was designed to test the effect of the number of pulses on fatigue. The declines in force during two repetitive, 150-train stimulation protocols that produced equal initial forces, one using 80-Hz trains and the other using 100-Hz trains, were compared. Despite a difference of 600 pulses (23.5%), the protocols produced similar rates and amounts of fatigue. In the second experiment, designed to test the effect of the number of pulses on the metabolic cost of contraction, 31P-NMR spectra were collected (n = 6) during two ischemic, eight-train stimulation protocols (80- and 100-Hz) that produced comparable forces despite a difference of 320 pulses (24.8%). No differences were found in the changes in P(i) concentration, phosphocreatine concentration, and intracellular pH or in the ATP turnover produced by the two trains. These results suggest that the effect of stimulation frequency on fatigue is related to the force produced, rather than to the number of activations. In addition, within the range of frequencies tested, increasing total activations did not increase metabolic cost.
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PMID:Effects of muscle activation on fatigue and metabolism in human skeletal muscle. 1196 Sep 48


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