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)

In the rat diaphragm muscle, the histochemical classification of type I, IIa, IIb, or IIx fibers was correlated with myosin heavy chain (MHC) immunoreactivity. Expression of MHC isoforms in single dissected fibers was also assessed electrophoretically. Most fibers (approximately 86%) expressed a single MHC isoform, and when present, coexpression of MHC-2X and MHC-2B isoforms was most prevalent. Type I and IIa fibers were the smallest, type IIb fibers were the largest, and type IIx fibers were intermediate. Succinate dehydrogenase (SDH) and calcium-activated myosin adenosinetriphosphatase (actomyosin ATPase) activities were measured with quantitative histochemical procedures. Type I and IIa fibers had the highest SDH activities, followed in rank order by type IIx and IIb fibers. Type I fibers had the lowest actomyosin ATPase activity, followed in rank order by type IIa, IIx, and IIb fibers. Across all fibers, there was an inverse relationship between fiber SDH activity and cross-sectional area and a positive correlation between fiber actomyosin ATPase activity and cross-sectional area. The SDH and actomyosin ATPase activities of muscle fibers were also inversely correlated. These phenotypic differences in SDH and ATPase activities may be important in determining the contractile and fatigue properties of different fiber types in the rat diaphragm muscle.
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PMID:SDH and actomyosin ATPase activities of different fiber types in rat diaphragm muscle. 859 23

Congestive heart failure is often associated with skeletal muscle abnormalities that contribute to early fatigue and acidosis. Up to the present time, however, the mechanisms responsible for these changes are unclear. Myocardial infarctions were produced by coronary ligation in adult Sprague-Dawley rats. At 20 weeks, 10 control rats, and 15 animals with heart failure [defined by elevated LVEDP (26.1 +/- 3.1 v 2.5 +/- 0.5 mmHg) and RV hypertrophy (300 +/- 21 g v 158 +/- 9 mg)] underwent in vivo measurements of total body, and soleus total protein and myosin heavy chain (MHC) synthesis by [3H]leucine constant infusion. Soleus muscle was also analysed for protein content, and MHC isoenzyme content by SDS-PAGE. Northern blotting also was used to determine levels of the mRNA's encoding type I, IIa, IIb, and IIx MHC, alpha-skeletal actin, COX III, SDH and GAPDH. Soleus muscles in heart failure rats were smaller than controls (112 +/- 6 v 126 +/- 5 mg) and the degree of atrophy was significant when corrected for body mass (0.38 +/- 0.02 v 0.46 +/- 0.02 mg/g. P = 0.007). Although there was no significant difference in plasma leucine flux (an index of whole-body protein synthesis), soleus muscle total and MHC synthesis was reduced in heart failure animals. Whereas the Type I MHC isoenzyme (beta MHC) was the only MHC detected in the soleus of control animals, type II MHC isoenzyme comprised 11.8 +/- 3.1% of the MHC in the heart failure group. Furthermore, steady-state mRNA levels encoding beta MHC were significantly depressed in the heart failure rats, where those encoding Types IIb and IIx MHC were increased. Steady-state mRNA levels of alpha-skeletal actin, cytochrome C oxidase (COX III) and succinate dehydrogenase (SDH) were also significantly depressed. This animal model of chronic heart failure is associated with quantitative and qualitative alterations in skeletal muscle gene expression that are similar to those reported in skeletal muscle of patients with chronic heart failure. The altered phenotype and impaired metabolic capacity may contribute to exercise intolerance in CHF.
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PMID:Alterations in skeletal muscle gene expression in the rat with chronic congestive heart failure. 887 78

Hypothyroidism (HYPO) often manifests as neuromuscular symptoms; however, little is known about its effects on the neuromuscular junction (NMJ). The present study examined changes in NMJ morphology and neuromuscular transmission failure (NTF) in the rat diaphragm muscle (Dimus) after 3 wk of HYPO. Three-color fluorescence immunocytochemistry and confocal microscopy were used to simultaneously visualize nerve terminals and axons, motor end plates, and myosin heavy chain isoform expression in Dimus fibers. NTF was assessed in vitro by comparing muscle fatigue induced by nerve with that induced by direct muscle stimulation. Diameters of axons innervating type I fibers were 30% smaller in the HYPO Dimus than in control (CTL). Planar areas of nerve terminals and end plates on type I and IIa fibers were 15-35% smaller in HYPO than in CTL. The extent of overlap between nerve terminals and end plates of type I fibers was 10% less in HYPO. Susceptibility to NTF during repetitive nerve stimulation was 20% greater in the CTL Dimus than in HYPO; however, changes in NMJ morphology could not fully account or the effect of HYPO on NTF.
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PMID:Alterations of diaphragm neuromuscular junctions with hypothyroidism. 888 59

The impact of hypothyroidism (Hyp) on myosin heavy chain (MHC) isoform expression, maximum specific force (P0), fatigability, and maximum unloaded shortening velocity (V0) was determined in the rat diaphragm muscle (Dia) at 0, 7, 14, 21, and 28 days of age. Hyp was induced by treating pregnant rats with 6-n-propyl-2-thiouracil (0.05% in drinking water) beginning at gestational day 10 and was confirmed by reduced plasma levels of 3,5,3'-triiodothyronine and thyroxine. MHC isoforms were separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and analyzed by densitometry. Isometric P0 and fatigue resistance of the Dia were measured in vitro at 26 degrees C, and V0 was determined at 15 degrees C with the slack test. Compared with control muscles, expression of MHC-slow was higher and expression of adult fast MHC isoforms was lower in Hyp Dia at all ages. The neonatal isoform of MHC continued to be expressed in the Hyp Dia until day 28. At each age, P0 and fatigability were reduced and V0 was slower in the Hyp Dia. We conclude that Hyp-induced alterations in MHC isoform expression do not fully predict the changes in Dia contractile properties.
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PMID:Hypothyroidism alters diaphragm muscle development. 894 17

Myocardial infarcts heal by scarring because myocardium cannot regenerate. To determine if skeletal myoblasts could establish new contractile tissue, hearts of adult inbred rats were injured by freeze-thaw, and 3-4.5 x 10(6) neonatal skeletal muscle cells were transplanted immediately thereafter. At 1 d the graft cells were proliferating and did not express myosin heavy chain (MHC). By 3 d, multinucleated myotubes were present which expressed both embryonic and fast fiber MHCs. At 2 wk, electron microscopy demonstrated possible satellite stem cells. By 7 wk the grafts began expressing beta-MHC, a hallmark of the slow fiber phenotype; coexpression of embryonic, fast, and beta-MHC continued through 3 mo. Transplanting myoblasts 1 wk after injury yielded comparable results, except that grafts expressed beta-MHC sooner (by 2 wk). Grafts never expressed cardiac-specific MHC-alpha. Wounds containing 2-wk-old myoblast grafts contracted when stimulated ex vivo, and high frequency stimulation induced tetanus. Furthermore, the grafts could perform a cardiac-like duty cycle, alternating tetanus and relaxation, for at least 6 min. Thus, skeletal myoblasts can establish new muscle tissue when grafted into injured hearts, and this muscle can contract when stimulated electrically. Because the grafts convert to fatigue-resistant, slow twitch fibers, this new muscle may be suited to a cardiac work load.
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PMID:Skeletal myoblast transplantation for repair of myocardial necrosis. 895 14

Spinal cord injured (SCI) individuals most often contract their injury at a young age and are deemed to a life of more or less physical inactivity. In addition to the primary implications of the SCI, severe SCI individuals are stigmatized by conditions related to their physically inactive lifestyle. It is unknown if these inactivity related conditions are potentially reversible and the aim of the present study was, therefore, to examine the effect of exercise on SCI individuals. Ten such individuals (six with tetraplegia and four with paraplegia; age 27-45 years; time since injury 3-23 years) were exercise trained for 1 year using an electrically induced computerized feedback controlled cycle ergometer. They trained for up to three times a week (mean 2.3 times), 30 min on each occasion. The gluteal, hamstring and quadriceps muscles were stimulated via electrodes placed on the skin over their motor points. During the first training bouts, a substantial variation in performance was seen between the subjects. A majority of them were capable of performing 30 min of exercise in the first bout; however, two individuals were only able to perform a few minutes of exercise. After training for 1 year all of the subjects were able to perform 30 min of continuous training and the work output had increased from 4 +/- 1 (mean +/- SE) to 17 +/- 2 Kilo Joules per training bout (P < 0.05). The maximal oxygen uptake during electrically induced exercise increased from 1.20 +/- 0.08 litres per minute measured after a few weeks habituation to the exercise to 1.43 +/- 0.09 litres per minute after training for 1 year (P < 0.05). Magnetic resonance cross sectional images of the thigh were performed to estimate muscle mass and an increase of 12% (mean, P < 0.05) was seen in response to 1 year of training. In biopsies taken before exercise various degrees of atrophy were observed in the individual muscle fibres, a phenomenon that was partially normalized in all subjects after training. The fibre type distribution in skeletal muscles is known to shift towards type IIB fibres (fast twitch, fast fatiguable, glycolytic fibres) within the first 2 years after the spinal cord injury. The muscle in the present investigation contained of 63% myosin heavy chain (MHC) isoform IIB, 33% MHC isoform IIA (fast twitch, fatigue resistant) and less than 5% MHC isoform I (slow twitch) before training. A shift towards more fatigue resistant contractile proteins was found after 1 year of training. The percentage of MHC isoform IIA increased to 61% of all contractile protein and a corresponding decrease to 32% was seen in the fast fatiguable MHC isoform IIB, whereas MHC isoform I only comprised 7% of the total amount of MHC. This shift was accompanied by a doubling of the enzymatic activity of citrate synthase, as an indicator of mitochondrial oxidative capacity. It is concluded that inactivity-associated changes in exercise performance capacity and skeletal muscle occurring in SCI individuals after injury are reversible, even up to over 20 years after the injury. It follows that electrically induced exercise training of the paralysed limbs is an effective rehabilitation tool that should be offered to SCI individuals in the future.
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PMID:Long-term adaptation to electrically induced cycle training in severe spinal cord injured individuals. 902 13

The effects of long-term dexamethasone treatment on diaphragm muscle were studied in female and male rats. Compared with pair-fed control animals, dexamethasone treatment did not significantly affect estrous cycling or peak serum estradiol levels; however, testosterone levels were significantly increased in females and decreased in males. Dexamethasone significantly reduced body and costal diaphragm weights, but to a lesser extent in females than in males. Reductions in diaphragm weight were proportional to reductions in body weight. In females and males, dexamethasone treatment significantly decreased diaphragm fiber (types I and II) cross-sectional area and the relative expression of myosin heavy chain isoform 2B. With the exception of type I fiber atrophy, these changes occurred to a lesser extent in females. Dexamethasone did not significantly affect specific forces. Dexamethasone significantly increased twitch one-half relaxation time and fatigue resistance indexes in males but not in females. In conclusion, the effects of long-term dexamethasone treatment were gender specific, with significantly fewer effects in females, and changes in serum testosterone levels were associated with these findings.
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PMID:Gender-specific effects of dexamethasone treatment on rat diaphragm structure and function. 902 7

Latissimus dorsi (LD) muscles of six canines were studied to assess changes induced by electrical conditioning and to quantify the capacity of these muscles to perform hemodynamic work. Muscles were conditioned using burst stimuli delivered over an 8-wk period. Contralateral LD were used as control. Muscles were tested in situ to simulate anticipated linear-pull cardiac assist conditions. This training process reduced muscle mass and cross-sectional area by 16 and 17%, respectively. Muscle phenotype shifted to a predominantly "slow" form by coordinate reduction of myosin heavy chain (MHC) 2A expression and increased expression of the MHC beta/slow form. Force generation was reduced by 54%, and contractile duration increased 13%. Fatigue resistance was markedly enhanced, and chronic stroke work increased from 0.19 to 0.72 mJ/g. The highest steady-state power output (2.06 mW/g) was obtained from one muscle fully converted to a slow phenotype. These data suggest that single LD trained via conventional techniques can provide energy sufficient for partial cardiac assistance but cannot sustain work levels needed to achieve total circulatory support.
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PMID:Functional properties of conditioned skeletal muscle: implications for muscle-powered cardiac assist. 927 56

The majority of patients with chronic heart failure (CHF) have a decreased exercise tolerance. It has not been well established if muscle fatigue is related to a peripheral myopathy with specific metabolic, histologic and biochemical abnormalities. CHF patients demonstrate depressed oxidative capacity and activation of anaerobic glycolysis, leading to a reduction in the energy substrates. In addition, the skeletal muscles of the lower limbs demonstrate a shift toward type IIb fibers. Many factors, such as prolonged immobilization, reduced blood flow and neuroendocrine activation, can be cited in order to explain the origin of this myopathy. Recent studies show that immobilization is not the only reason for modifications in skeletal muscle composition, since patients with disuse atrophy show an increased percentage in myosin heavy chain I, while IIb is decreased. The opposite pattern is observed in CHF. It would appear that several factors such as deconditioning, prolonged immobilization and reduced blood flow, may produce muscular atrophy. The reasons behind specific changes in fibre composition may be found in metabolic factors such as insulin resistance, TNF levels and dysfunction of the ergo-metabolo muscle receptors.
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PMID:[Skeletal musculature modifications and mechanisms of fatigue in chronic heart failure]. 928 Jul 30

In respiratory muscles, force generation and shortening depend on the cyclical interaction of actin and myosin (cross-bridge cycling). During cross-bridge cycling, adenosine triphosphate (ATP) is hydrolysed. The globular head region of the myosin heavy chain (MyHC) possesses both the binding site to actin and the site for ATP hydrolysis. Therefore, the MyHC is both a structural and enzymatic protein. Different isoforms of MyHC are expressed in skeletal muscle fibres, and these MyHC isoforms provide mechanical and metabolic diversity. In the present study, the relationships between MyHC isoform expression in single rat diaphragm muscle fibres and their mechanical and energetic properties were evaluated. The expression of MyHC isoforms in single diaphragm muscle fibres was identified using electrophoretic and immunohistochemical techniques. Cross-bridge cycling kinetics in diaphragm muscle fibres clearly depend on MyHC isoform expression, and these differences are interpreted in the context of Huxley's two-state cross-bridge model. It is concluded that the unique mechanical and energetic properties of myosin heavy chain isoforms are designed to accomplish different motor behaviours of the diaphragm muscle, and that, as a result of these unique properties, a selective recruitment of diaphragm muscle fibres is essential to avoid fatigue.
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PMID:Cross-bridge kinetics in respiratory muscles. 931 83


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