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

Contractile properties of the adductor pollicis muscle were examined in 9 normal volunteers and 7 patients with histochemically proven myophosphorylase deficiency (McArdle's disease). Fatiguing contractions were produced by supramaximal stimulation of the ulnar nerve, delivered over a range of frequencies, to allow further examination of the mechanisms responsible for the premature fatigue in patients. The excessive reductions in force, demonstrated in patients at all frequencies, were not associated at high frequencies (50 and 100 Hz) with excessive declines in excitation (measured as compound muscle action potential). These results demonstrate that, in patients, myofibrillar activation failure occurs over and above that due to excitation failure. Abnormal slowing of relaxation mechanisms was also confirmed. These findings appear consistent with the hypothesis of inhibition of various ATPases by metabolic products. The observed, clear differences between normal subjects and myophosphorylase-deficient patients constitute the basis of an objective screening procedure for this and other glycolytic disorders.
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PMID:Myofibrillar activation failure in McArdle's disease. 280 26

The roles of cAMP and inorganic phosphate (Pi) in the regulation of muscle glycogenolysis during exercise have been investigated in humans using the needle biopsy technique. The fraction of phosphorylase a in resting muscle was as a mean 23%, but the rate of glycogenolysis was extremely low. Epinephrine infusion increased cAMP in muscle by 3-fold and transformed 80% of phosphorylase to the a form. Despite this, the rate of glycogenolysis was only 5-10% of the maximum rate of phosphorylase a (Vmax a) determined in vitro. Isometric exercise for 25 s at 66% MVC or electrical stimulation for 50 s at 20 Hz transformed about 53% and 80% of phosphorylase in the a form. The rate of glycogenolysis ranged between 50-90 mmol.kg-1.dm.min-1 and was close to Vmax of phosphorylase a determined in vitro. No significant difference in the rate of glycogenolysis in muscle was observed after isometric exercise to fatigue without and with epinephrine infusion, respectively. Apparently the rate of glycogenolysis in muscle is not solely related to the fraction of phosphorylase in the a form. Several factors could be responsible for allosteric and/or substrate regulation. The results in the present studies can be explained on the basis of substrate regulation of phosphorylase activity, provided that Pi is present in a limiting amount at the active site of phosphorylase in muscle at rest. It is concluded that transformation of phosphorylase b to a is important but alone is not adequate for a high activity and thus for a high rate of glycogenolysis in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of cyclic AMP and inorganic phosphate in the regulation of muscle glycogenolysis during exercise. 285 69

Clinical and biochemical findings in skeletal muscle in 11 patients with chronic fatigue myalgia syndromes of unknown aetiology are reported. All patients had severe asthenia for from one to 10 years with greatly limited exercise capacity and protracted exhaustion after minor exercise. Diffuse myalgia was prominent and was exacerbated for hours to days after exercise. Assay of skeletal muscle carnitine, phosphorylase, all glycolytic enzymes and the mitochondrial marker enzymes monoamine oxidase, isocitrate dehydrogenase and cytochrome oxidase were normal. These findings lend no support to the presence of a major defect in muscle intermediary energy pathways in this syndrome.
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PMID:Chronic fatigue and myalgia syndrome: mitochondrial and glycolytic studies in skeletal muscle. 303 60

Calcium-mediated phosphorylase kinase activation has been studied in the rat flexor digitorum brevis, a fast-twitch oxidative-glycolytic skeletal muscle that exhibits a robust inward Ca2+ current [Can J. Physiol. Pharmacol. 63:958-965, 1985]. This system provided an opportunity to compare the regulation of contraction and activation of phosphorylase by extracellular and intracellular sources of Ca2+. In muscles repetitively stimulated at 21 degrees, there appeared to be a close correlation between the control of contraction and phosphorylase activation. Blocking extracellular Ca2+ entry promoted an inactivation of phosphorylase and diminished the elevation of resting tension, which in untreated muscles ensues with the onset of fatigue. The response of muscles stimulated at 37 degrees was in distinct contrast. Phosphorylase, following initial rapid activation, was then briskly inactivated despite the continuation of a near-maximal contractile response. An elevation in resting tension during stimulation was observed at 37 degrees but was a transitory response in comparison to what was seen at 21 degrees. Blocking the entry of external Ca2+ inhibited this response. Sarcolemmal Ca2+ channel blockers had no effect on the observed phosphorylase response at 37 degrees, but phosphorylase was already nearly fully inactivated before their effects were manifested on contraction. Thus, at this temperature there is a clear dissociation between Ca2+-mediated regulation of contraction and the production of metabolic energy by enhanced glycogenolysis. This appears to occur because, although Ca2+ induces phosphorylase activation, a subsequent, but rapid non-Ca2+-mediated event promotes inactivation, even while Ca2+-mediated contraction is being sustained.
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PMID:Calcium-dependent regulation of phosphorylase activation in a fast-twitch oxidative-glycolytic skeletal muscle. 334 81

Muscle phosphorylase deficiency (McArdle's disease) has conventionally been considered a disorder of glycogenolysis, and the associated impairment in oxidative metabolism has been largely overlooked. Muscle glycogen normally is the primary oxidative fuel at exercise work loads requiring more than 75-80% of maximal O2 uptake (VO2max). Evidence is presented to support the hypothesis that a limited flux through the Embden-Myerhof pathway in McArdle's disease reduces the capacity to generate NADH required to support a normal VO2max. The extent of the oxidative defect is substrate dependent; i.e., it can be partially corrected by increasing the availability of alternative oxidative substrates (e.g., glucose, free fatty acids) to working muscle. Experiments employing modification of substrate availability closely link the hyperkinetic circulatory response to exercise (i.e., an abnormally large increase in O2 transport to skeletal muscle) and the premature muscle fatigue and cramping of McArdle patients with their oxidative impairment and suggest that a metabolic common denominator in these abnormal responses may be a pronounced decline in the muscle phosphorylation potential ([ATP]/[ADP][Pi]). The hyperkinetic circulation likely is mediated by the local effects on metabolically sensitive skeletal muscle afferents and vascular smooth muscle of K+, Pi, or adenosine or a combination of these substances released excessively from working skeletal muscle. The premature muscle fatigue and cramping of McArdle patients does not appear to be due to depletion of ATP but is associated with an increased accumulation of Pi and probably ADP in skeletal muscle. Accumulations of Pi and ADP are known to inhibit the myofibrillar, Ca2+, and Na+-K+-ATPase reactions.
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PMID:The pathophysiology of McArdle's disease: clues to regulation in exercise and fatigue. 352 13

The fast-twitch posterior latissimus dorsi muscle of normal and genetically dystrophic chickens was subjected to continuous indirect electrical stimulation at 10 Hz for periods of 4-8 weeks. To sustain this in vivo nerve stimulation an internally implantable miniature stimulator device was designed. This regime of stimulation caused complete fatigue of the normal muscle within 5 min of its initiation. The dystrophic muscles maintained a very small degree of contractile activity during this initial phase. Tangible twitching of the muscle returned in 5 week birds between 3 and 5 days and in 10 week birds between 11 and 16 days after implantation. After 4 weeks of stimulation, no significant change was measured in the time-to-peak of the isometric twitch response, nor in the half-relaxation time. The resistance to fatigue was significantly increased in the stimulated muscles when tested with a series of tetani at 40 Hz. The mean fibre area was decreased, in all muscles stimulated for longer than 3 weeks, in comparison to their contralateral controls, except where fibre splitting in dystrophic birds abnormally reduced the control value. The majority fibre type of the muscle was changed from type IIB to IIA. The histochemical reactions for both NADH-linked oxidation and phosphorylase were distinctly increased in the stimulated muscles. In normal muscle, stimulation increased somewhat the number of nuclei per unit area and changed their intracellular distribution, so that a greater proportion was found adjacent to the sarcolemma. The normal posterior latissimus dorsi muscle responded to chronic stimulation with increases of 3-6-fold in its acetylcholinesterase (AChE) activity. The maximum change in AChE occurred after 2 weeks stimulation; a steady level, 3 times that of the control unstimulated muscle, persisted at later times. Chronic stimulation suppressed the over-production of AChE that is characteristic of dystrophic chicken fast-twitch muscle, to attain a level comparable to the AChE activity in a stimulated normal muscle. Stimulation exerted a strong normalizing influence on dystrophic muscle, as assessed morphologically. The characteristic fibre rounding, fibre hypertrophy and myonuclear proliferation were reduced. This influence was most marked where the stimulation was initiated before the major pathological changes had occurred, but was also significant when commenced in strongly affected birds of 10-11 weeks.
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PMID:Low frequency chronic electrical stimulation of normal and dystrophic chicken muscle. 379 78

Alterations in enzyme activities involved in muscle energy metabolism and the muscle fiber type distribution were investigated in six subjects, ranging in age from 19-23 years, following short-term, high intensity exercise. Changes in the vastus lateralis muscle were studied prior to exercise and approximately 24 h after each of 2 consecutive days of supramaximal cycling exercise (120% VO2 max) performed intermittently as 1-min work to 4-min rest until fatigue or until 24 repetitions had been completed. The results indicated that there were no changes (P greater than 0.05) in maximal in vitro activities for representative enzymes of beta-oxidation (3-hydroxyacyl CoA dehydrogenase, HAD), the citric acid cycle (succinic dehydrogenase, SDH), glucose phosphorylation (hexokinase, HK), glycogenolysis (total phosphorylase, PHOSPH), or glycolysis (phosphofructokinase, PFK; pyruvate kinase, PK; lactate dehydrogenase, LDH) in spite of the large increase in carbohydrate utilization and glycolytic flux rate. In addition, although no change in fiber type distribution was found in the pre-exercise biopsy between days, an acute reduction (P less than 0.05) in type I fiber distribution occurred with exercise. It is concluded that supramaximal exercise performed on a short-term basis does not alter the enzymatic profile or the fiber type distribution when measured 24 h following the activity.
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PMID:Fiber type distribution and maximal activities of enzymes involved in energy metabolism following short-term supramaximal exercise. 609 Mar 24

The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle has been investigated using the needle biopsy technique. Preliminary studies showed that the activity of phosphorylase in vitro was dependent upon the concentration of inorganic phosphate (Pi) used in the assay system. The Km of phosphorylase a for Pi was found to be 26.2 mmol/l, and that of (a+b) (assayed in the presence of saturating AMP) was 6.8 mmol/l. Because of the difference in Km the apparent percentage of a to (a+b) activity varies with the Pi concentration used in the assay system. Phosphorylase a and (a+b) activities were therefore adjusted to saturating Pi concentrations. The ratio of the activities in this case is independent of the Pi concentration and constitutes a minimal estimate of the fraction of phosphorylase molecules in the a form. The fraction of phosphorylase in the a form in resting muscle was as a mean 22%. Despite nearly a quarter of the phosphorylase being in the a form glycogenolytic activity is extremely low. It is proposed that the concentration of Pi at the active site of the enzyme is low compared to the Km for this of either form of the enzyme, and is limiting to activity. A Pi concentration in resting muscle of 1-3 mmol/l was calculated. During epinephrine infusion at rest 90% of the phosphorylase was transformed to the a form but only a moderate increase in the glycogenolytic rate occurred. This rate approximated to 5-10% of the maximum rate of the enzyme (Vmaxa). During prolonged epinephrine infusion the glycogenolytic rate decreased despite the continuance of 90% or more of the phosphorylase in the a form. In contrast to epinephrine infusion prolonged ischemia resulted in a decrease in the mole fraction of phosphorylase a and simultaneously in an increase of the glycogenolytic rate. During isometric and dynamic exercise there was a rapid transformation of phosphorylase b to a paralleled by pronounced increase in the rate of glycogen breakdown. The increased rate of glycogenolysis during isometric exercise was close to the Vmax of phosphorylase a in vivo. When either form of exercise was continued to fatigue/exhaustion, a re-transformation of phosphorylase a to b was observed. During dynamic exercise cAMP in the muscle increased two fold. This increase was blocked by the prior administration of propranolol.+
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PMID:The regulation of glycogen phosphorylase and glycogen breakdown in human skeletal muscle. 613 34

It has been postulated that the power spectral shift in the surface EMG during fatigue is due to accumulation of muscle lactate. This hypothesis has been directly tested by measuring such shift in 3 patients with myophosphorylase deficiency who performed sustained isometric contractions of the quadriceps muscle. It was found that the spectral shift in these patients was greater than that in normal subjects, rendering lactate as a cause of this phenomenon very unlikely. The mechanism of excessive fatiguability in myophosphorylase deficiency is thought to be due to failure of excitation of the muscle membrane; further support for this postulate is provided and it is contended that accumulation of extracellular potassium ions may explain the phenomena of spectral shift in normals and myophosphorylase deficient patients and the excessive fatiguability in the latter.
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PMID:Muscle fatigue in myophosphorylase deficiency: power spectral analysis of the electromyogram. 620 Feb 96

Leg muscles of adult rats were stimulated chronically at a low-frequency, and the histochemical reactions of various enzymes (succinic dehydrogenase, mitochondrial alpha-glycerophosphate dehydrogenase, phosphorylase, alkali-ATPase and acid-ATPase), capillary density, resistance to fatigue, and contractile properties were studied. Following stimulation, the histochemical properties of muscle fibres in the fast extensor digitorum longus (EDL) and tibialis anterior (TA) muscles became similar to those of the majority of fibres in the slow soleus muscle. In the soleus muscle, the histochemical properties of the few fast type fibres became similar to the majority of 'slow' fibres so that its fibre composition was homogeneously 'slow'. The stimulated fast muscles also had higher capillary density and were more resistant to fatigue than normal. Despite the prolonged stimulation, the twitch duration of the fast muscles was little changed. This result differs from the findings obtained previously for the rabbit and cat, which show that slowing of contraction can be achieved by low-frequency activity of similar duration. Thus it may be that there is a species difference regarding the readiness with which the transformation of fast to slow muscles can be brought about.
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PMID:Effects of low-frequency electrical stimulation on fast and slow muscles of the rat. 621 64


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