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

Since broxaterol, a new beta 2-agonist, has been shown to improve contractility of fatigued canine diaphragm in vitro, a controlled, randomized study was designed to assess its effects on fatigued canine diaphragm in vivo, and compare these to the expected inotropic effects of aminophylline. Diaphragm fatigue was induced in 21 dogs using electrophrenic stimulation at 20 Hz until transdiaphragmatic pressure (Pdi) at 20 Hz was reduced to about 50% of its original value. After stabilization of fatigue, animals were randomized in three groups. Aminophylline-treated animals received an intravenous bolus of 20 mg/kg, broxaterol-treated animals were given an initial bolus of 100 micrograms/kg, and control animals obtained an equal load of saline. After 3 h, aminophylline-treated animals and broxaterol-treated animals received a second dose of 20 mg/kg and 200 micrograms/kg, respectively, whereas control animals received a second dose of saline. Pdi was measured every 30 min for 6 h. At therapeutic serum levels, theophylline did not affect Pdi at any stimulation frequency compared with control conditions. In contrast, broxaterol administration resulted in a significant (p less than 0.05) and long-lasting increase in Pdi at low stimulation frequencies. Pdi at 20 Hz thus increased by 20 +/- 16% 90 min after the first bolus, and by 36 +/- 18% 90 min after the second dose. We conclude that (1) broxaterol promotes recovery of low-frequency fatigue in a dose-dependent way, and (2) theophylline does not improve the force output of fatigued canine diaphragm in vivo.
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PMID:Effects of broxaterol and theophylline on fatigued canine diaphragm in vivo. A randomized, controlled study. 135 66

Studies in adult animal and human subjects have suggested that the methylxanthine drugs can delay the onset or attenuate the severity of diaphragmatic fatigue. We have investigated the effect of aminophylline and caffeine on the pressure-generating capacity of the fatigued diaphragm in 1-mo-old piglets. Measurements of ventilation, transdiaphragmatic pressure, blood gases and pH, diaphragmatic electromyogram, diaphragmatic pressure-frequency curve (PdiFC), diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 90 min of inspiratory resistive loaded breathing (IRL), and again 30 min after methylxanthine infusion while still on IRL. IRL resulted in a significant decrease in minute ventilation secondary to a fall in tidal volume. Spontaneously generated transdiaphragmatic pressure increased 7-fold from baseline. EMG activity increased to both segments of the diaphragm. Abdominal expiratory muscle activity was noted after the onset of IRL and was accompanied by a fall in end-expiratory lung volume. The PdiFC was significantly decreased from baseline after 90 min of IRL, demonstrating diaphragmatic fatigue. Aminophylline did not alter the PdiFC of the diaphragm. Diaphragmatic electromyogram and tidal volume increased. No change in diaphragmatic blood flow was demonstrated after infusion of aminophylline. Serum theophylline levels averaged 117 +/- 11 mumol/L (21 +/- 2 micrograms/mL). Caffeine administration did not alter the PdiFC or the diaphragmatic electromyogram during IRL. Blood flow to both segments of the diaphragm decreased after caffeine infusion. Serum caffeine levels averaged 86 +/- 30 mumol/L (16.6 +/- 5.9 micrograms/mL).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of methylxanthines on diaphragmatic fatigue in the piglet. 148 Apr 60

Hypoxic, hypercapnic acidosis (HHA) decreases tension and enhances fatigue in hamster diaphragm in vitro. We hypothesized that theophylline would decrease the harmful effect of HHA. Hamster diaphragm strips were studied in Krebs solution aerated with 21% O2 and 12% CO2. The force-frequency responses and the tension and relaxation of brief, submaximal contractions were studied. Mild fatigue was produced by a series of 45 submaximal contractions, after which recovery of force was followed for 15 min. Theophylline (0.55 mM) was added at the time of exposure to HHA (early theophylline) in half the strips and at the end of the fatigue run (late theophylline) in the others. In contrast to our hypothesis, early theophylline had a limited effect on force production in unfatigued HHA diaphragm strips and resulted in lower force production in the recovery period. Late theophylline improved force in the recovery period for low-frequency contractions. Thus the effect of theophylline in the setting of HHA depended on the time it was added and was beneficial only if added after the muscle stopped contracting.
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PMID:The effect of theophylline on hypoxic, hypercapnic hamster diaphragm muscle in vitro. 202 50

The traditional role of theophylline as a bronchodilator has been expanded by recent findings that suggest this drug has more than smooth muscle relaxant properties. Several investigators indicate that theophylline has an inotropic effect on respiratory muscle, causing enhanced muscular contraction and prevention of muscle fatigue. In animal studies, the drug enhanced respiratory muscle contraction by 15-20%, with levels in the upper end of the therapeutic range (15-20 mg/L). Results of studies in healthy volunteers and patients with lung disease, however, are conflicting. Five clinical trials demonstrated increased diaphragmatic contractility, whereas seven trials showed no effect, with five referring to the diaphragm and the remaining two to the sternomastoid muscle. Disparity in outcomes may be attributed to differences in patient populations, study designs, and techniques used to determine diaphragmatic contractility. Few long-term trials exist that document significant clinical benefit. Theophylline may prove to be of value in selected populations, such as adults with hypercapnic obstructive lung disease.
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PMID:The effect of theophylline on respiratory muscle contractility and fatigue. 220 60

We studied the effect of aminophylline on twitch tension (TT) and intracellular pH (pHi) in isolated rat diaphragm strips that were fatigued, hypercapnic, or hypoxic. Superfused muscles were directly stimulated at 0.5 Hz. The pHi was measured from distribution volumes of dimethyl-oxazolidinedione. Fatigue was induced by intermittent tetanic stimulation. Hypercapnia and hypoxia were produced by altering superfusate carbon dioxide tension (PCO2) or oxygen tension (PO2). Aminophylline (1.0 mmol.l-1) reversed the twitch decay seen during fatigue or hypercapnic acidosis, and caused partial recovery of twitch depression during hypoxia. Muscle fatigue was not due to an intracellular acidosis. Both hypercapnia and hypoxia lowered pHi. Aminophylline did not alter pHi in unstimulated muscles, but caused a significant fall in pHi in stimulated muscles that were fatigued or hypoxic. High dose aminophylline improved twitch tension in diaphragm strips that were fatigued, acidotic, or hypoxic. Twitch potentiation was not due to an intracellular alkalosis. Aminophylline lowered pHi in stimulated muscle, and thus, theoretically, could sometimes be harmful in the treatment of muscle fatigue.
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PMID:The effect of aminophylline on function and intracellular pH of the rat diaphragm. 228 69

Theophylline improves diaphragmatic contractility of the respiratory muscles both in isolated muscle preparations, as well as in animals and normal human beings. Furthermore, theophylline restores diaphragmatic fatigue and prevents fatigue of the diaphragm when given prophylactically. Finally, it was recently shown that theophylline improves diaphragmatic function in COPD patients, all of whom were CO2 retainers (PaCO2 53 +/- 3 mm Hg) and hypoxemic (PaO2 57 +/- 8 mm Hg). Patients improved transdiaphragmatic pressure and were less susceptible to fatigue. Presently the mechanisms of action of theophylline regarding its effects on diaphragmatic function are not fully elucidated. Experimental evidence, however, suggests that theophylline may have an effect on transmembrane calcium movements by blocking adenosine receptors.
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PMID:Effect of theophylline on respiratory muscle function. 241 Feb 4

Aminophylline has been demonstrated to increase in vitro contractility in skeletal muscle, including diaphragm. In vivo studies report significant increases in diaphragm contractility in patients with chronic obstructive pulmonary disease but only small increases in control subjects. The present study determined the effects of aminophylline on strength and fatigability in the diaphragm, the biceps brachii, and the quadriceps of normal individuals. Seven healthy subjects were tested with placebo and drug conditions on separate days in a randomized, double-blind fashion. Mean theophylline levels of 15 +/- 2 mg/L SD were maintained by constant intravenous infusion. Strength of the diaphragm was measured as maximum inspiratory pressure. Strength of the biceps and quadriceps were measured isometrically during arm flexion (90 degrees) and leg extension (115 degrees) against an electronic load cell. Fatigue was measured as the decrease in tension during a 30-second contraction and during a 6-minute period of alternating 5-second maximal contraction and 5-second rest. Therapeutic levels of theophylline had no effect on strength or fatigability during a maximal contraction in any muscle group studied.
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PMID:In vivo effects of theophylline on diaphragm, bicep, and quadricep strength and fatigability. 320 50

Recent investigations have shown that theophylline improves diaphragmatic contractility of the respiratory muscles in isolated muscle preparations in animals and in normal human subjects. It has also been demonstrated that theophylline can reverse diaphragmatic fatigue and prevent fatigue of the diaphragm when given prophylactically. These effects have also been demonstrated in patients with severe chronic obstructive pulmonary disease, all of whom retained CO2 (PaCO2 53 +/- 3 mm Hg) and had hypoxia (PaO2 57 +/- 8 mm Hg). Theophylline, which increases respiratory muscle strength and delays the onset of diaphragmatic fatigue therefore could be a very useful agent in the treatment of patients with chronic airway obstruction.
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PMID:Effect of theophylline on diaphragmatic muscle function. 329 24

The effect of intravenous aminophylline on the contractility of the sternomastoid muscle was measured in the fresh state and after the induction of significant fatigue in five normal subjects. Fatigue was produced by repetitive isometric neck flexion, for two seconds every four seconds at 70% of the maximum voluntary contractile force, continued until exhaustion. Each subject performed three experiments, one to two weeks apart, in random order. In experiment 1 fatiguing exercise and recovery were completed without aminophylline; in experiment 2 intravenous aminophylline was started 30 minutes before exercise and continued throughout the 60 minute recovery period; and in experiment 3 intravenous aminophylline was started immediately after the end of exercise. Aminophylline did not influence the frequency-force relationships, relaxation rate, or maximum voluntary contractile force in the fresh muscle. After fatiguing exercise there was a relatively selective reduction in force response to stimulation frequencies of less than 30 Hz, with little alteration in forces at higher frequencies--that is, low frequency fatigue--and this effect was present for the entire one hour study period. Aminophylline given before or immediately after fatigue did not influence the recovery of either low frequency fatigue or maximum voluntary contractile force. Aminophylline at therapeutic concentrations had no significant effect on the contractility or fatiguability of the normal human sternomastoid muscle.
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PMID:Effect of aminophylline on fatigue of the sternomastoid muscle in man. 370 78

The influence of theophylline and the related drug caffeine on the mechanical performance of fatigued muscle fibre isolated from semitendinosus muscle of Rana temporaria (2.5-6.7 degrees C) was investigated. The fibre was stimulated supramaximally to produce I s fused tetani and 2 s and 10 s partially fused tetani at intervals of 10 min. Fatigue was produced by shortening the contraction interval to 15 and 30 s. This caused a 15-20% decline in the maximum tension during fused tetanus and a 40-50% decline during partially fused tetanus. Theophylline and caffeine (0.1-0.5 mM) did not change the maximum tension developed by the fatigued fibre during fused tetanization. Both drugs, however, markedly increased the tension output of the fatigued muscle fibre during partially fused tetanus. It was observed that the increase in partially fused tetanic tension by theophylline and caffeine was associated with an increase in the degree of fusion. This later effect was even more pronounced in the presence of diethyl-stilboestrol. It is concluded that these drugs may not reverse the metabolic changes caused by fatigue, since they are unnable to increase fused tetanic force of a fatigued muscle fibre. The increase in partially fused tetanic tension of a fatigued muscle fibre by these drugs is probably due to enhancement of the activator calcium release from the sarcoplasmic reticulum in response to stimulation.
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PMID:Fatigue in frog skeletal muscle fibres and effects of methylxanthine derivatives. 387 23


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