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

In rats with left ventricular (LV) hypertrophy, we investigated whether abnormalities of skeletal muscle could result in reduced exercise tolerance in the absence of reduced cardiac function. LV pressure overload was induced by partial constriction of the abdominal aorta (AC) with controls subjected to sham operation. Cardiac and skeletal muscle function and blood flow were assessed in vivo 3 and 6 weeks later. AC induced LV hypertrophy of 41% and 37% at 3 and 6 weeks post-operation. In AC rats, cardiac index was 31 +/- 8 and 35 +/- 4 ml/min/100 g at 3 and 6 weeks compared to 38 +/- 4 and 34 +/- 2 ml/min/100 g in controls (N.S.). Fatigue index of the soleus (type-I rich) muscle in AC rats was reduced by 14% (P < 0.05) at both time points, while that of the tibialis anterior (mixed fiber) muscle was unchanged at 3 weeks but reduced by 18% (P < 0.05) at 6 weeks. Function of the extensor digitorum longus (type-IIB rich) muscle was unaltered at both time points. Blood flow at rest was paradoxically increased in muscles which exhibited increased fatigue susceptibility. At 3 weeks, blood flow during fatigue stimulation was reduced by 33% in the soleus muscle; the only muscle to exhibit impaired fatigue resistance at this time point. Blood flow during stimulation remained unaltered in the EDL and TA muscles. Thus, impaired fatigue resistance was observed in skeletal muscle with high oxidative and oxidative glycolytic fiber content during the compensatory phase of LV hypertrophy, prior to overt cardiac dysfunction. A selective impairment of blood flow to these muscles during exercise may play a causal role in exercise intolerance.
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PMID:Impaired skeletal muscle fatigue resistance in rats with pressure overload-induced left ventricular hypertrophy. 874 26

We have presented an assay for measuring the rate of sarcoplasmic reticulum (SR) Ca2+ uptake and Ca2+ release in skeletal muscle homogenates using the fluorescent Ca2+ probe Fura-2. Using this assay, we investigated the effects of an elevated temperature (40 degrees C) and lowered pH (6.8), two factors proposed to be involved in skeletal muscle fatigue, on SR Ca2+ uptake. The EDL muscle was found to have a higher rate of Ca2+ uptake than the soleus (34%). Exposure of the muscles to a raised temperature, but not a reduced pH, resulted in a reduction in the rate of Ca2+ uptake in both the EDL and soleus homogenates. This uptake process was blocked by cyclopiazonic acid (CPA) a specific inhibitor of the major transport protein of the sarcoplasmic reticulum, the Ca(2+)-ATPase. Calcium release was induced using AgNO3 after loading of the vesicles during the uptake process. It was found that AgNO3 was only effective in producing Ca2+ release in the EDL muscles. The soleus muscles did not release Ca2+ under varying [Mg2+] or with Hg2+ substitution for Ag+, suggesting that fast- and slow-twitch muscle fibres require different conditions for maximum Ca2+ release, or that different isoforms of the Ca2+ release channels are present in the different fibres.
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PMID:A method for measuring sarcoplasmic reticulum calcium uptake in the skeletal muscle using Fura-2. 886 73

Complete occlusion of blood flow to rat hind limb by tourniquet was used to study the effects of total ischemia for 1, 2, and 3 h on contractile function and metabolic behaviour of two muscles composed predominantly of either fast-twitch (extensor digitorum longus, EDL) or slow-twitch (soleus, SOL) fibres. Percent loss in twitch force (Pt) was greater (p < 0.05) in SOL than EDL during the first 45 min of ischemia. Following 1 h of ischemia, ATP concentration was lower (p < 0.05) than in the contralateral control (20.8 +/- 2.0 vs. 26.4 +/- 1.5 mmol/kg dry weight). Thereafter, the decline in ATP was greater, with approximately 95% depleted by 3 h of ischemia (1.46 +/- 0.46 mmol/kg dry weight). The effect of ischemia on ATP levels in the SOL was similar to ATP levels in the EDL, 1 h of ischemia also resulted in a large decrement in PCr, from 50.1 +/- 2.9 to 11.7 +/- 2.4 mmol/kg dry weight, and a large increase in lactate, from 25.0 +/- 3.0 to 114 +/- 10 mmol/kg dry weight. As ischemia was prolonged, only lactate was increased (p < 0.05) both at 2 h (171 +/- 12 mmol/kg dry weight) and 3 h (208 +/- 5.4 mmol/kg dry weight). Similar trends were found for SOL. By 3 h of ischemia, glycogen was depleted (p < 0.05) by 88% in EDL and 92% in SOL, respectively. These results support the hypothesis that both high energy phosphate transfer and anerobic glycolysis are of major importance in defending ATP hemostasis, particularly during the 1st h of ischemia, and that the resulting metabolic disturbances are responsible for the large fatigability observed. The mechanisms underlying the greater resistance to fatigue observed for the SOL compared with the EDL during the earlier period of ischemia remain uncertain.
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PMID:Metabolic and contractile responses of fast- and slow-twitch rat skeletal muscles to ischemia. 904 44

Creatine kinase (CK) is a key enzyme for maintaining a constant ATP/ADP ratio during rapid energy turnover. To investigate the role of CK in skeletal muscle fatigue, we used isolated whole muscles and intact single fibers from CK-deficient mice (CK(-/-)). With high-intensity electrical stimulation, single fibers from CK(-/-) mice displayed a transient decrease in both tetanic free myoplasmic [Ca(2+)] ([Ca(2+)](i), measured with the fluorescent dye indo-1) and force that was not observed in wild-type fibers. With less intense, repeated tetanic stimulation single fibers and EDL muscles, both of which are fast-twitch, fatigued more slowly in CK(-/-) than in wild-type mice; on the other hand, the slow-twitch soleus muscle fatigued more rapidly in CK(-/-) mice. In single wild-type fibers, tetanic force decreased and [Ca(2+)](i) increased during the first 10 fatiguing tetani, but this was not observed in CK(-/-) fibers. Fatigue was not accompanied by phosphocreatine breakdown and accumulation of inorganic phosphate in CK(-/-) muscles. In conclusion, CK is important for avoiding fatigue at the onset of high-intensity stimulation. However, during more prolonged stimulation, CK may contribute to the fatigue process by increasing the myoplasmic concentration of inorganic phosphate.
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PMID:Is creatine kinase responsible for fatigue? Studies of isolated skeletal muscle deficient in creatine kinase. 1078 53

1. In skeletal muscle, dihydropyridine (DHP) receptors control both Ca(2+) entry (L-type current) and internal Ca(2+) release in a voltage-dependent manner. Here we investigated the question of whether elimination of the skeletal muscle-specific DHP receptor subunit gamma1 affects excitation-contraction (E-C) coupling. We studied intracellular Ca(2+) release and force production in muscle preparations of a mouse deficient in the gamma1 subunit (gamma-/-). 2. The rate of internal Ca(2+) release at large depolarization (+20 mV) was determined in voltage-clamped primary-cultured myotubes derived from satellite cells of adult mice by analysing fura-2 fluorescence signals and estimating the concentration of free and bound Ca(2+). On average, gamma-/- cells showed an increase in release of about one-third of the control value and no alterations in the time course. 3. Voltage of half-maximal activation (V(1/2)) and voltage sensitivity (k) were not significantly different in gamma-/- myotubes, either for internal Ca(2+) release activation or for the simultaneously measured L-type Ca(2+) conductance. The same was true for maximal Ca(2+) inward current and conductance. 4. Contractions evoked by electrical stimuli were recorded in isolated extensor digitorum longus (EDL; fast, glycolytic) and soleus (slow, oxidative) muscles under normal conditions and during fatigue induced by repetitive tetanic stimulation. Neither time course nor amplitudes of twitches and tetani nor force-frequency relations showed significant alterations in the gamma1-deficient muscles. 5. In conclusion, the overall results show that the gamma1 subunit is not essential for voltage-controlled Ca(2+) release and force production.
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PMID:Excitation-contraction coupling in skeletal muscle of a mouse lacking the dihydropyridine receptor subunit gamma1. 1138 98

In the present work, we investigate age-dependent changes in isometric endurance in response to repetitive stimulation in single intact fast- and slow-twitch muscle fibers from young and old mice. To examine this issue we performed in vitro experiments in manually dissected EDL and soleus muscle fibers. We examined the force generation capacity of fibers in response to two stimulation protocols characterized by different inter-tetanic intervals, named short (1-s) and long interval (3.65-s). Fatigability was measured according to the fatigue index (FI, ratio between the maximum tension recorded in the last over the first tetanus in a train of pulses), the time course of the FI and sag (gradual decrease in force during a partially fused tetanic contraction). Fibers were classified according to the FI using two different criteria previously used in the literature (first criterion: FI > or = 1, 075-099, 0.5-074 and < 0.5; second criterion: FI > or = 1, 0.75-0.99, 0.25-0.74 and < 0.25). The fatigue index distribution recorded in the population of fibers corresponding to EDL and soleus muscles from young and old mice studied with the short and long interval protocols was not statistically different. In summary, these results support the concept that the decline in mechanical performance with aging is not related with changes in fatigability of individual fast- or slow twitch muscles fibers.
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PMID:Age-dependent fatigue in single intact fast- and slow fibers from mouse EDL and soleus skeletal muscles. 1138 21

Soleus and EDL muscles of rats were examined following hindlimb unloading. Some of the rats were given beta-GPA, a creatine analog which depletes high-energy phosphates in muscle tissue, in their food. The contractile properties and fatigue resistance of these muscles were studied, with and without incubation in calcium solution. The increased fatigue resistance after beta-GPA feeding was less in calcium-free solution.
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PMID:Contractile properties of rat skeletal muscles after hindlimb unloading and beta-GPA administration. 1154 Feb 63

To examine changes in contractile properties and mechanisms of fatigue during submaximal nontetanic skeletal muscle activity, in situ perfused soleus (60-min protocol) and extensor digitorum longus (EDL; 10-min protocol) muscles of the rat were electrically stimulated intermittently at low frequency. The partly fused trains of contractions showed a two-phase change in appearance. During the first phase, relaxation slowed, one-half relaxation time increased, and maximal relaxation first derivative of force (dF/dt) decreased. Developed force during the trains was reduced and was closely related to the rate of relaxation in this first phase. During the second phase, relaxation became faster again, one-half relaxation time decreased, and force returned to resting levels between contractions in a train. In contrast, developed force remained reduced, so that peak force of the contractions was 51% (soleus) and 30% (EDL) of control. In the soleus muscle, the changes in contractile properties were not related to ATP, creatine phosphate, or lactate content. The changes in contractile properties fit best with a mechanism of fatigue involving changes in Ca(2+) handling by the sarcoplasmic reticulum.
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PMID:Muscle contractile properties during intermittent nontetanic stimulation in rat skeletal muscle. 1170 82

It was already documented that acute hypoxemia reduces the oxidative stress following static as well as dynamic handgrip bouts in humans. Then, we examined if chronic hypoxemia could produce the same effect in patients suffering from chronic respiratory insufficiency. In rats, we studied the respective consequence of a one-month exposure to normobaric hypoxia on two muscles (soleus, SOL, and extensor digitorum longus, EDL) which have high and low aerobic metabolism, respectively. Compared to healthy humans, the resting level of erythrocyte reduced glutathione (GSH) was significantly lower in chronic hypoxemic patients, and after a handgrip contraction sustained at 50% of maximal until exhaustion the GSH level and plasma thiobarbituric acid reactive substances (TBARS) did not vary. A 20-min period of oxygen supplementation partly restored the post-handgrip oxidative stress. Compared to control rats, SOL muscle of hypoxemic animals had lower intra-muscular resting level of GSH; after a 3-min muscle stimulation (MS) leading to fatigue, TBARS did not vary in SOL and EDL and the GSH decrease was absent in SOL whereas it persisted in EDL. We concluded that chronic hypoxemia depressed the fatigue-induced oxidative stress, the effects prevailing in muscles having a high oxygen demand.
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PMID:Depressed fatigue-induced oxidative stress in chronic hypoxemic humans and rats. 1523 68

Although it is well established that patients suffering from malaria experience skeletal muscle problems (contracture, aches, fatigue, weakness), detailed studies have not been performed to investigate changes in the contractile function and biochemical properties of intact and skinned skeletal muscles of mammals infected with malaria. To this end, we investigated such features in the extensor digitorium longus (EDL, fast-twitch, glyocolytic) and in the soleus (SOL, slow-twitch, oxidative) muscles from mice infected with Plasmodium berghei. We first studied maximal tetanic force (T(max)) produced by intact control and malaria-infected muscles before, during and after fatigue. Triton-skinned muscle fibres were isolated from these muscles and used to determine isometric contractile features as well as a basic biochemical profile as analysed by silver-enhanced SDS-PAGE. We found that the T(max) of intact muscles and the maximal Ca2+-activated force (F(max)) of Triton-skinned muscle fibres were reduced by approximately 50% in malarial muscles. In addition, the contractile proteins of Triton-skinned muscle fibres from malarial muscles were significantly less sensitive to Ca2+. Biochemical analysis revealed that there was a significant loss of essential contractile proteins (e.g. troponins and myosin) in Triton-skinned muscle fibres from malarial muscles as compared to controls. The biochemical alterations (i.e., reduction of essential contractile proteins) seem to explain well the functional modifications resolved in both intact muscles and Triton-skinned muscle fibres and may provide a suitable paradigm for the aetiology of muscle symptoms associated with malaria.
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PMID:Functional and biochemical modifications in skeletal muscles from malarial mice. 1572 39


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