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)

Pharyngeal dilator muscles are critical for maintaining upper airway patency in the neonatal period. The present study examined in vitro the contractile properties of a pharyngeal dilator muscle, the sternohyoid, in 1-7-day-old piglets (n = 24). Isometric contraction and half-relaxation times were 36.7 +/- 1.1 and 30.9 +/- 1.2 msec, respectively. Twitch potentiation ('staircase phenomenon') and post-tetanic potentiation were noted following repetitive stimulation. During prolonged repetitive stimulation with a standard (40 Hz) fatigue test, muscle force declined gradually over time, with loss of half of the initial force occurring over 138 +/- 11 sec, and a 2-min fatigue index (ratio of force at 2 min to initial force) of 0.52 +/- 0.03. An additional 10 piglets were studied at ages of 14-20 days. Muscle from older piglets had comparable isometric twitch kinetics as that of younger animals. However, sternohyoid muscle from the older piglets had worse endurance than muscle from the younger animals, as indicated by a shorter time required for force to decrease by half (86 +/- 10 sec, P < 0.01) and a lower 2-min fatigue index (0.36 +/- 0.03, P < 0.01). These data indicate that for the sternohyoid muscle of the newborn piglet (a) physiological properties are consistent with moderate to fast contraction with good endurance, (b) force potentiates during repetitive twitch stimulation and following a brief period of tetanic stimulation, and (c) there is worsening of endurance but no change in isometric twitch kinetics with increasing age during the first weeks of life.
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PMID:Pharyngeal dilator muscle contractile and endurance properties in neonatal piglets. 851 9

Treatment with the fluorinated steroid triamcinolone (TR) induced type IIb fiber atrophy and the contractile profile of a slow muscle in rat diaphragm. In contrast, the nonfluorinated steroid prednisolone (PR) caused myogenic changes without fiber atrophy, and increased fatigability. The aim of the present study was to investigate the extent to which these changes were reversed 2 mo after discontinuation of treatment. Adult rats were randomly assigned to receive saline, PR 1.25 or 5 mg/kg, or TR 0.25, 0.5, or 1 mg/kg, intramuscularly daily during 4 wk. Administration of TR resulted in severe loss of body weight and dose-dependent mortality. During recovery, body weight in the TR groups increased gradually, still remaining reduced compared with the other groups. Two months after discontinuation of treatment, diaphragm weight was increased in proportion to body weight. Twitch characteristics, maximal tetanic force, force-frequency curve, and fatigue resistance of isolated diaphragm bundles were similar in all groups. Histologic examination of the diaphragm revealed no gross abnormalities in the PR and TR groups. Mild but significant type IIb fiber atrophy was still present in the diaphragm and gastrocnemius muscle of all TR-treated animals. In conclusion, recovery of alterations in morphology of respiratory and peripheral skeletal muscles induced by administration of TR is prolonged.
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PMID:Recovery of corticosteroid-induced changes in contractile properties and morphology of rat diaphragm. 856 31

The purpose of this study was to determine whether diaphragmatic fatigue occurs after voluntary hyperpnea to task failure. Ten male subjects were asked to breathe at minute ventilation (V1) equal or slightly greater than 60% of their 12-s maximum voluntary ventilation (MVV) until task failure. Transdiaphragmatic pressure (Pdi) was measured during bilateral supramaximal stimulation of the phrenic nerves before and 10, 30, 60, and 120 min after hyperpnea. For the group, V1 averaged 107.1 +/- 7.1 L/min (SE) (range, 71-154 L/min), which represented 60 +/- 2% of the MVV. After voluntary hyperpnea, seven of the 10 subjects displayed at least a 10% reduction in twitch Pdi during transcutaneous stimulation, while all 10 subjects had a greater than 10% reduction in twitch Pdi during cervical magnetic stimulation. For the group, transcutaneous twitch Pdi was significantly decreased from 27.0 +/- 1.9 at baseline to 21.4 +/- 1.7 cm H2O (p < 0.0001) at 10 min posthyperpnea. Magnetic twitch Pdi was also significantly decreased from 36.0 +/- 2.1 at baseline to 28.7 +/- 1.9 cm H2O (p < 0.0001) at 10 min posthyperpnea. Twitch Pdi remained significantly decreased from baseline for at least 1 h after hyperpnea. After hyperpnea, the mean percentage decrease from baseline in twitch Pdi was virtually identical with the two stimulation techniques. The percentage fall in twitch Pdi after hyperpnea with the two techniques was not significantly correlated (r = 0.4). In conclusion, long-lasting contractile fatigue of the diaphragm reliably occurs after voluntary hyperpnea at levels sufficient to induce task failure. Cervical magnetic stimulation can detect diaphragmatic fatigue after a fatiguing task, but the results obtained with this technique may differ from those obtained with transcutaneous stimulation in individual subjects.
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PMID:Diaphragmatic fatigue following voluntary hyperpnea. 868 Jul 1

The aim of the study was to examine if the twitch interpolation technique could be used to objectively measure fatigue in the quadriceps muscle in subjects performing submaximally. The 'true' maximum isometric quadriceps torque was determined in 21 healthy subject using the twitch interpolation technique. Then an endurance test was performed in which the subjects made repeated isometric contractions at 50% of the 'true' maximum torque for 4 s, separated by 6 s rest periods. During the test, the force response to single electrical stimulation (twitch amplitude) was measured at 50% and 25% of the estimated maximum torque. In 10 subjects, the test was repeated 2-4 weeks later. Twitch amplitudes at 50% of maximum torque declined exponentially with time in 20 of 21 subjects. The distribution of the exponential rate constant was skewed with a mean of 4.6 h-1 and range of 0.3-21.5 h-1. After logarithmical transformation, the distribution of the exponential rate constant fitted closely to a normal distribution, and the inter-individual variation was SD = 1.15 compared to an intra-individual variation of 0.29. The coefficient of correlation for repeated determination was 0.91 (P < 0.001, n = 10). In conclusion, the twitch technique can be used for objectively measuring fatigue of the quadriceps muscle.
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PMID:The twitch interpolation technique for study of fatigue of human quadriceps muscle. 875 91

Abdominal muscles are the principal muscles of active expiration. To investigate the possibility of abdominal muscle low-frequency fatigue after maximal ventilation in humans, we stimulated the nerve roots supplying the abdominal muscles. We used a magnetic stimulator (Magstim 200) powering a 90-mm circular coil and studied six normal subjects. To assess the optimum level of stimulation and posture, we stimulated at each intervertebral level between T7 and L1 in the prone, supine, and seated positions. At T10, we used increasing power outputs to assess the pressure-power relationship. Care was taken to avoid muscle potentiation. Twitch gastric pressure (Pga) was recorded with a balloon-tipped catheter. Mean (+/-SD) baseline twitch Pga measured with the subjects in the prone position at T10 was 23.5 +/- 5.4 cmH2O. Within-occasion mean twitch Pga coefficient of variation was 4.6 +/- 1.1%. Twitch Pga was measured with the subjects in the prone position with stimulation over T10 before and after 2 min of maximal isocapnic ventilation (MIV). Twenty minutes after MIV, mean twitch Pga fell by 17 +/- 9.1% (P = 0.03) and remained low 90 min after MIV. We conclude that after maximal ventilation in humans there is a reduction of twitch Pga and, therefore, of low-frequency fatigue in abdominal muscles.
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PMID:Abdominal muscle fatigue after maximal ventilation in humans. 890 56

Effects of increased hydrostatic pressure (range 0.1-10 MPa) on isometric twitch and tetanic contractions of single, intact, frog muscle fibres were examined at 4, 11 and 21 degrees C and at different stages of fatigue. Twitch tension was potentiated by pressure at all temperatures, but the extent of potentiation was more pronounced at higher temperatures (34% MPa-1 at 21 degrees C, compared to 8% MPa-1 at 4 degrees C). Tetanic tension was depressed by pressure at 4 degrees C (approximately 0.7% MPa-1) but was potentiated by pressure at 21 degrees C (approximately 0.4% MPa-1). The effect of hydrostatic pressure on the tetanic tension was dependent on the fatigue status of the muscle fibre: during the early stages of fatigue (when tetanic tension was depressed by < 20%), high pressure produced a tension depression (as in an unfatigued muscle fibre), whilst during the later stages of fatigue high pressure induced a significant potentiation of tetanic. Our results support the suggestion that excitation-contraction coupling and contractile activation are impaired during late fatigue. Pressure-effects were basically similar to caffeine-effects under a variety of conditions, suggesting that an enhancement of Ca2+ release may be contributory to potentiation of twitch tension and, in severely, fatigued muscle, potentiation of tetanic tension. In the rested state and during early fatigue the main effect of pressure is an inhibition of the crossbridge cycle.
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PMID:Effects of hydrostatic pressure on fatiguing frog muscle fibres. 899 82

We previously demonstrated that broxaterol enhanced recovery of fatigued canine diaphragm. The aim of this study was to compare the inotropic effects of salbutamol and broxaterol on fatigued canine diaphragm. Low-frequency fatigue was induced in 14 mongrel dogs by electrophrenic stimulation, which was continued until transdiaphragmatic pressure (Pdi) at 20 Hz was reduced by 50% or for 1 h. After stabilization of fatigue, the animals received a bolus (18.5 microg/kg) of either broxaterol or salbutamol, followed by a continuous infusion (0.43 microg/kg/min). A second bolus of 74.0 microg/kg, followed by a continuous infusion of 1.72 microg/kg/min, was given after 90 min. Both drugs significantly increased twitch Pdi. Twitch Pdi measured 90 min after the first and second doses of broxaterol increased by 28 +/- 23% and 42 +/- 34%, respectively, whereas the salbutamol-induced increase was clearly smaller (9 +/- 10% and 17 +/- 15%, respectively). Broxaterol increased Pdi at 20 Hz by 25 +/- 28% with the first dose and by 29 +/- 21% with the second dose. In contrast, salbutamol did not alter Pdi at 20 Hz. Neither drug affected Pdi at 100 Hz. We conclude that broxaterol promoted recovery of low-frequency fatigue of the canine diaphragm in vivo in a dose-dependent manner, whereas salbutamol only minimally improved force production by the fatigued diaphragm.
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PMID:Broxaterol increases force output of fatigued canine diaphragm more than salbutamol. 900 9

Phosphorylation of myosin regulatory light chain (R-LC) increases the sensitivity of skinned skeletal muscle fibers to low Ca2+ activation. The purpose of this study was to determine whether phosphorylation of R-LC-mediated increases in Ca2+ sensitivity provides a molecular basis for potentiated twitch forces observed during fatigue of intact mammalian skeletal muscle. Tetanic stimulation for 120 s reduced peak tetanic force (Po) of mouse extensor digitorum longus (EDL) muscle by 74 +/- 2%. Despite high frequency fatigue (HFF), Pt was potentiated by 18 +/- 3% when R-LC phosphorylation (in moles phosphate per mole R-LC) was increased from 0.11 +/- 0.05 (rest) to 0.52 +/- 0.04 by 15 s of stimulation. Thereafter Pt declined below resting values despite high levels for R-LC phosphorylation (0.80 +/- 0.04 after 120 s of stimulation). In separate experiments, 10 min of stimulation, which reduced Po and Pt by 80 +/- 2 and 67 +/- 3%, respectively, was used to induce low frequency fatigue (LFF) in mouse EDL muscle. During LFF, long-lasting reductions in Pt were evident despite near-normal levels for Po (79 +/- 2 and 98 +/- 2% of controls, respectively). Application of conditioning stimuli (CS) increased R-LC phosphate content of fatigued muscles from 0.15 +/- 0.03 (rest) to 0.56 +/- 0.03 (stimulated) and potentiated Pt by 26 +/- 2% compared with LFF. Twitch potentiation during LFF was transient, lasting only as long as R-LC was phosphorylated above resting values for fatigued muscles. Overall, our data showing potentiated twitch forces concomitant with elevations in R-LC phosphate content during either HFF or LFF of mouse EDL muscle suggest that this molecular event counters reduced twitch forces during these forms of fatigue. Our results may be explained by R-LC phosphorylation induced increases in Ca2+ sensitivity for twitch force production in fatigued muscle.
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PMID:Phosphorylation of myosin and twitch potentiation in fatigued skeletal muscle. 904 41

Primary hyperparathyroidism, characterized by hypersecretion of parathyroid hormone (PTH) leading to hypercalcemia and relative hypophosphatemia, is quite common in the elderly. Most patients with primary hyperparathyroidism have only mild hypercalcemia and are symptomless. But others experience various other organ diseases. Primary hyperparathyroidism is also associated with cardiovascular abnormalities, including QT interval shortening, heart block, cardiac arrhythmias, hypertension, myocardial hypertrophy, myocardial calcification and, though rarely, with valvular heart disease. We described a case of primary hyperparathyroidism associated with cardiac abnormalities. An 82-year-old male presented with the complaints of chest discomfort, fatigue, general weakness, nausea and vomiting over a period of months and was admitted in July 1996. Physical examination with heart auscultation showed a pansystolic murmur over the right sternal border and apex region, and a blowing diastolic murmur over the left sternal border. Biochemistry profiles revealed elevations of serum calcium (14.3 mg/dl) and chloride/phosphate ratio (> 33). Endocrinological studies showed elevations of serum PTH-C (4.8 ng/ml) and PTH-intact (705 pg/ml) concentrations. Kidney ultrasonography revealed a left renal stone. A spine X-ray revealed spondylosis and a compression fracture of the lumbar-spine with osteoporotic change. Thyroid ultrasonography and Thallium (Tl201)-technetium (Tc99m) subtraction scan showed parathyroid adenoma in the low pole of the right thyroid bed. Parathyroid aspiration cytology revealed few and discrete cells. Echocardiogram revealed moderate to severe aortic valvular calcification as well as stenosis with moderate aortic regurgitation, mitral regurgitation and myocardial calcification. The patient received parathyroidectomy one month later. During his postoperative days, he suffered from muscle twitching with positive Trousseau's sign and Chvostek's sign. The patient received calcium carbonate and vitamin D for hypocalcemia, diltiazem and capoten for his heart problems. A repeated echocardiogram two months after surgery showed no improvement of valvular calcification.
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PMID:Primary hyperparathyroidism with cardiac abnormalities: a case report. 950 84

Agents that block many types of K+ channels (e.g., the aminopyridines) have substantial inotropic effects in skeletal muscle. Specific blockers of ATP-sensitive and Ca2+-activated K+ channels, on the other hand, do not, or minimally, alter the force of nonfatigued muscle, consistent with a predominant role for voltage-gated K+ channels in regulating muscle force. To test this more directly, we examined the effects of peptide toxins, which in other tissues specifically block voltage-gated K+ channels, on rat diaphragm in vitro. Twitch force was increased in response to alpha-, beta-, and gamma-dendrotoxin and tityustoxin Kalpha (17 +/- 6, 22 +/- 5, 42 +/- 14, and 13 +/- 5%; P < 0.05, < 0.01, < 0.05, < 0.05, respectively) but not in response to delta-dendrotoxin or BSA (in which toxins were dissolved). Force during 20-Hz stimulation was also increased significantly by alpha-, beta-, and gamma-dendrotoxin and tityustoxin Kalpha. Among agents, increases in twitch force correlated with the degree to which contraction time was prolonged (r = 0.88, P < 0.02). To determine whether inotropic effects could be maintained during repeated contractions, muscle strips underwent intermittent 20-Hz train stimulation for a duration of 2 min in presence or absence of gamma-dendrotoxin. Force was significantly greater with than without gamma-dendrotoxin during repetitive stimulation for the first 60 s of repetitive contractions. Despite the approximately 55% higher value for initial force in the presence vs. absence of gamma-dendrotoxin, the rate at which fatigue occurred was not accelerated by the toxin, as assessed by the amount of time over which force declined by 25 and 50%. These data suggest that blocking voltage-activated K+ channels may be a useful therapeutic strategy for augmenting diaphragm force, provided less toxic blockers of these channels can be found.
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PMID:Peptide toxin blockers of voltage-sensitive K+ channels: inotropic effects on diaphragm. 1006 17


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