Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A broadly held opinion is that fatigue is not due to an insufficient supply of ATP to the energy consuming mechanisms because tissue [ATP] always remains at least one order of magnitude higher than Km for ATP of any ATPase. In general these findings also suggest that ATP consumption is well balanced with ATP regeneration even in the fatigued muscles. This balance is achieved by down-regulation of ATP consumption. Potentially this down-regulation could be accomplished by any product of the ATPase reaction and the role of Pi and H+ accumulation in this regulation has been discussed in the literature. The purpose of this paper is to describe known compartmentalization of ATP regeneration systems in muscle cell, their importance in the regulation of [adenine nucleotide] in the vicinity of ATPases and how such local ATP regeneration maybe important in the etiology of muscle fatigue. Available experimental evidence suggests that the binding of creatine kinase and glycolytic enzymes in the vicinity of sites where ATP is hydrolyzed and functional coupling between these ATP regenerating mechanisms and ATPase can generate ATPase microenvironments that have an important role in the regulation of ATPase function. Main function of this ATP regeneration is to keep the local ADP/ATP ratios favorable for ATPase function, which seems to be especially important when ATPase turnover is high. Unfortunately, the maximum rate of local ATP regeneration relative to that of ATP hydrolysis in vivo is not known, mainly because in vitro determinations underestimate this value due to a decrease in the fractional of loosely abound enzyme to the preparation during isolation procedure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The importance of ATPase microenvironment in muscle fatigue: a hypothesis. 764 8

Biopsies from the vastus lateralis muscle were obtained from three astronauts before and after two 5-day flights and from five astronauts before and after one 11-day flight (space shuttle flights: STS-32, -33, and -34). Muscle fibers from two separate samples from each biopsy were classified as type I and II or as type I, IIA, and IIB by using qualitative myofibrillar adenosinetriphosphatase (ATPase) staining. Cross-sectional area (CSA), number of capillaries per fiber, and the activities of succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (GPD), and myofibrillar ATPase were determined from one sample of fibers of each myofibrillar ATPase type. Postflight biopsies had 6-8% fewer type I fibers than preflight. Mean fiber CSAs were 16-36% smaller after the 11-day flight with the relative effect being type IIB > IIA > I. Mean fiber CSAs were 11 and 24% smaller in type I and II fibers after 5 days of flight. Myofibrillar ATPase activities increased in type II but not in type I fibers after flight, whereas SDH activity was unaffected in either fast or slow fibers. GPD activity in type I fibers was approximately 80% higher (P > 0.05) postflight compared with preflight. Myofibrillar ATPase/SDH ratios in type II fibers were higher after than before flight, suggesting that some fast fibers were more susceptible to fatigue after flight. The GPD/SDH ratios were elevated in some type I fibers after spaceflight. The number of capillaries per fiber was 24% lower after than before flight, whereas the number of capillaries per unit CSA of muscle tissue was unchanged. These data suggest that adaptations in the size, metabolic properties, and vascularity of muscle fibers can occur rapidly in the space environment. These adaptations were qualitatively similar to those observed in animals after actual or simulated spaceflight conditions for short periods.
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PMID:Human fiber size and enzymatic properties after 5 and 11 days of spaceflight. 764 6

The extent to which treatment with low doses of the nonfluorinated steroid methylprednisolone affects diaphragm contractility and morphology is unknown. In the present study, we compared the effects of equipotent doses of methylprednisolone and deflazacort, an oxazoline derivate of prednisolone with less systemic side-effects on bone structure and carbohydrate metabolism. Twenty six male adult rats were randomized to receive daily saline (control), methylprednisolone 0.4 mg.kg-1 or deflazacort 0.5 mg.kg-1 i.m. Contractile properties and histopathology were measured after a 6 week treatment period. During treatment, body weight increased in control and methylprednisolone-treated animals, but decreased by 4.2 +/- 1.1% (mean +/- SD) in the deflazacort group. Similarly, diaphragm mass in the deflazacort group was decreased compared to control and methylprednisolone groups. Twitch tension and twitch characteristics of isolated diaphragm bundles were similar in the three groups. Maximal tetanic tension was decreased in the deflazacort group. The force-frequency curve of the deflazacort bundles shifted downwards compared to control. Fatigue occurring during this protocol was greatest in the methylprednisolone- and deflazacort-treated animals. Microscopic examination revealed no gross abnormalities in the three groups. Histochemical analysis after staining for myosin adenosine triphosphatase (ATP-ase) showed that in the deflazacort group cross-sectional area of type I, IIa and IIb fibres were decreased. We conclude that low doses of methylprednisolone caused subtle and negligible changes in rat diaphragm contractile properties without affecting fibre dimensions, while deflazacort at an equipotent dose induced generalized fibre atrophy and changes in diaphragm contractility.
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PMID:Rat diaphragm contractility and histopathology are affected differently by low dose treatment with methylprednisolone and deflazacort. 765 57

1. The goal of this study was to characterize the fatigability, contractile relaxation properties, electrophysiological responses, and histochemical properties of the human paralyzed soleus muscle to determine its relative plasticity. 2. Acute (< 6 wk, n = 3) and chronic (> 1 yr, n = 10) paralyzed individuals had the tibial nerve activated with a 20-Hz square wave delivered for 330 ms every second for 4 min. The soleus muscle peak torque, one-half relaxation time (1/2RT), normalized maximum rate of relaxation (nMRR), and mass muscle action-potential amplitude (M wave) were computed every 30 s. A soleus muscle biopsy was evaluated for myosin adenosine triphosphatase enzyme (ATPase; pH 9.4, 4.6, and 4.2) and nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR). 3. In the chronically paralyzed group the torque was significantly reduced within 30 s of the fatigue protocol. The 1/2RT and nMRR were also significantly changed within 30 s, supporting that muscle relaxation was prolonged. No significant changes were present at comparable times during the same 4-min fatigue protocol applied to the acutely paralyzed soleus muscle. M-wave amplitude was significantly reduced in the chronic group, but only at 3 min of the fatigue protocol. Conversely, no significant changes occurred to the M waves of the acute group. 4. The correlation was high between torque and nMRR (r = 0.88-0.97) and torque and 1/2RT (r = 0.88-0.96) for each chronic subject. A close association was also found between 1/2RT and nMRR (r = 0.88-0.92) for each chronic subject. Because these variables changed minimally in the acutely paralyzed group, a lower correlation was present (r = 0.45-0.52). 5. Torque was weakly correlated to M-wave amplitude (r = 0.55) for the chronically paralyzed group. The greatest change in torque occurred at a time (0-65 s) when the least amount of change occurred in the M-wave amplitude, suggesting that the source of fatigue was within the contractile mechanism and not attributable to neuromuscular transmission compromise. 6. Despite a close association between torque and relaxation properties during fatigue of the chronically paralyzed soleus muscle, there was a significant dissociation after 5 min of recovery. Torque recovered to 60%, whereas the relaxation properties were consistently fully recovered. This suggests that the mechanism causing torque reduction covaried with the mechanism leading to prolonged relaxation during fatigue, but during recovery the two mechanisms no longer covaried. M-wave amplitude was also completely recovered at 5 min despite continued torque depression.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fatigability, relaxation properties, and electromyographic responses of the human paralyzed soleus muscle. 766 32

The diaphragm is a vital respiratory muscle in the sleeping infant. Any changes in diaphragm fiber type number or size could represent either a primary developmental delay or a secondary reaction to increased workload, and could give a clue as to the pathogenesis of sudden infant death syndrome (SIDS). We therefore quantitated by point counting on ATPase histochemistry the numbers and areas of type 1 and 2 fibers in the diaphragm, external intercostal and psoas muscles of 37 SIDS and 20 control infants. The amount of slow, fast and fetal myosin in the diaphragm and psoas muscles was measured by electrophoresis to check the ATPase quantitation. There were fewer type 1 fibers in SIDS (median 30.0%) compared with control (median 40.0%) infants (p < 0.02), whereas the diameter of type 1 fibers in SIDS (median 33.9 microns) was larger than in control (median 30.3 microns) infants (p < 0.007). The total cross-sectional area occupied by type 1 and 2 fibers was similar in both groups. No changes were found in the external intercostal or psoas. The amount of slow and fast myosins correlated well with type 1 and type 2 fibers, respectively. The finding of fewer type 1 (fatigue-resistant) fibers of large diameter in SIDS diaphragms suggests that differences in muscle fiber types may predispose these infants to diaphragm fatigue and respiratory failure.
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PMID:Differences in diaphragm fiber types in SIDS infants. 781 77

To directly assess the possible role of ADP in muscle fatigue, we have studied the effect of physiological MgADP levels on maximum Ca(2+)-activated isometric force and unloaded shortening velocity (Vus) of single skinned fiber segments from rabbit fast-twitch (psoas) and slow-twitch (soleus) muscles. MgADP concentration was changed in a controlled and well-buffered manner by varying creatine (Cr) in solutions, which also contained MgATP, phosphocreatine (PCr), and creatine kinase (CK). To quantify ADP as a function of Cr added, we determined the apparent equilibrium constant (K') of CK for the conditions of our experiments (pH 7.1, 3 mM Mg2+, 12 degrees C): K' = (sigma [Cr]. sigma [ATP])/(sigma [PCr]. sigma [ADP]) = 260 +/- 3 (SE). In this manner, ADP was altered essentially as occurs during stimulation in vivo but without the concomitant changes in pH and P(i), which affect force and Vus. As ADP (and Cr) was increased, force and Vus decreased in both fiber types; at the highest ADP level used, 200 microM, normalized force was 96.6 +/- 1.7% for psoas (n = 6) and 93.7 +/- 2.8% for soleus (n = 6), and Vus was 80.4 +/- 2.4% for psoas and 91.3 +/- 7.7% for soleus. Diffusion-reaction calculations indicated that radial gradients of metabolite concentrations within fibers could not explain the small effects of ADP on fiber mechanics, and experiments verified that metabolite levels were well buffered within fibers by the CK reaction. Exogenous CK was added to bathing solutions at 290 U/ml, threefold above that necessary to maintain Vus independent of CK concentration; in the absence of PCr and exogenous CK, at least a fourfold increased MgATP was necessary to maintain Vus at the control level. Adenylate kinase activity was not detectable; thus myofibrillar adenosine-triphosphatase and exogenous CK activities were the major determinants of nucleotide levels within activated cells. Cr alone (in absence of PCr and exogenous CK) also decreased force and Vus, presumably by a nonspecific mechanism. Over the physiological range, altered ADP had little or no effect on force or Vus in well-buffered conditions. It is therefore likely that other factors decrease force and Vus during muscular fatigue.
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PMID:Effect of physiological ADP concentrations on contraction of single skinned fibers from rabbit fast and slow muscles. 786 87

By means of histological method and ultrasound cardiographic (UCG) examination, the left-right ratio of transectional area of muscle fiber of latissimus dorsi muscle (LDM) after non-dynamic cardiomyoplasty was 77.4 +/- 11.7% in Group I (3 weeks after operation), and 78.4 +/- 11.6% atrophy and hyperplasia of LDM, but the basical structure was retained. The ejection fraction (EF) decreased significantly after operation (P < 0.05), but the difference between two groups was non- significant. Also, dynamic cardiomyoplasty was performed on a sheep. UCG showed the increased cardiac systolic function after operation. ATPase, succinodehydrogenase (SDH) and PAS examination implied the strengthening of fatigue-resistant ability in skeletal muscles after long-term electrical stimulation. So cardiomyoplasty is suggested to be a supplementary measure in treating end-stage heart failure.
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PMID:Cardiac function and histological changes after non-dynamic cardiomyoplasty and preliminary study of dynamic cardiomyoplasty. 786 91

To examine the effect of exercise on sarcoplasmic reticulum function in muscle tissue of different fibre composition, adult male Wistar rats weighing 388 +/- 23 g (x +/- SE) ran intermittently on a treadmill until fatigue. Fatigue was induced by 15-20 min of running performed at 52 m/min on an 8 degrees incline in periods of 2.5 min of exercise separated by 2 min of recovery. Analysis of sarcoplasmic reticulum Ca2+ ATPase activity determined in homogenates indicated no difference (p > 0.05) between age-matched control and exercised tissue for the soleus (SOL; 0.121 +/- 0.012 vs. 0.156 +/- 0.018 mumol.mg-1 protein.min-1), red gastrocnemius (RG; 0.381 +/- 0.022 vs. 0.354 +/- 0.022), or white gastrocnemius (WG; 0.526 +/- 0.05 vs. 0.471 +/- 0.031). Similarly, both total ATPase and Mg2+ ATPase activities were unaffected by the exercise in any of the tissues examined. Exercise also failed to alter sarcoplasmic reticulum Ca2+ uptake in homogenates of the SOL (1.43 +/- 0.15 vs. 1.38 +/- 0.19 nmol.mg-1 protein.min-1), RG (3.74 +/- 0.29 vs. 3.59 +/- 0.24), and WG (5.98 +/- 0.48 vs. 5.41 +/- 0.50). At fatigue, glycogen depletion was similar in all tissue types and amounted to 65.1% in the SOL (172 +/- 9 vs. 60 +/- 16 mmol.glucosyl units-1.kg-1 dry weight), 74.4% in RG (164 +/- 8 vs. 42 +/- 6), and 79% in the WG (167 +/- 9 vs. 35 +/- 9). It is concluded that exercise by itself does not alter sarcoplasmic reticulum Ca2(+)-sequestering function in tissues of primarily different fibre composition when determined in homogenates in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preservation of sarcoplasmic reticulum Ca2(+)-sequestering function in homogenates of different type composition following sprint activity. 788 89

We analyzed the masticatory muscles (masseter, temporal, medial pterygoid and lateral pterygoid muscles) of Bovidae and Cervidae (Artiodactyla) for the histochemical characteristics of their fiber types. Analysis of muscle fiber types in the present study was based on the staining reaction for SDH, Sudan black B, alpha-GPDH, and myosin-ATPase after alkaline preincubations. Histochemical properties were found to contribute to masticatory function, including a slow-twitch fatigue resistant activity derived from the high percentage of red fibers, in spite of the differences in the distributions of fiber types in three portions (superficial, medial and profound portions) of each masticatory muscle. These results indicate a correlation between the histochemical profiles of individual masticatory muscles in these species and their functions during jaw movements.
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PMID:Differentiation of histochemical properties of masticatory muscles in Bovidae and Cervidae (Artiodactyla). 804 63

This study examined changes in contractile, biochemical, and histochemical properties of slow antigravity skeletal muscle after a 6-day spaceflight mission. Twelve male Sprague-Dawley rats were randomly divided into two groups: flight and ground-based control. Approximately 3 h after the landing, in situ contractile measurements were made on the soleus muscles of the flight animals. The control animals were studied 24 h later. The contractile measurements included force-velocity relationship, force-frequency relationship, and fatigability. Biochemical measurements focused on the myosin heavy chain (MHC) and myosin light chain profiles. Adenosine-triphosphatase histochemistry was performed to identify cross-sectional area of slow and fast muscle fibers and to determine the percent fiber type distribution. The force-velocity relationships of the flight muscles were altered such that maximal isometric tension (Po) was decreased by 24% and maximal shortening velocity was increased by 14% (P < 0.05). The force-frequency relationship of the flight muscles was shifted to the right of the control muscles. At the end of the 2-min fatigue test, the flight muscles generated only 34% of Po, whereas the control muscles generated 64% of Po. The flight muscles exhibited de novo expression of the type IIx MHC isoform as well as a slight decrease in the slow type I and fast type IIa MHC isoforms. Histochemical analyses of flight muscles demonstrated a small increase in the percentage of fast type II fibers and a greater atrophy of the slow type I fibers. The results demonstrate that contractile properties of slow antigravity skeletal muscle are sensitive to the microgravity environment and that changes begin to occur within the 1st wk. These changes were at least, in part, associated with changes in the amount and type of contractile protein expressed.
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PMID:Effect of spaceflight on skeletal muscle: mechanical properties and myosin isoform content of a slow muscle. 804 58


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