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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

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

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

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 diseases which are commonly complicated by hypercapnic respiratory failure also compromise the respiratory muscles in several ways. Increased work of breathing, mechanical disadvantage, neuromuscular disease, impaired nutritional status, shock, hypoxemia, acidosis, and deficiency of potassium, magnesium, and inorganic phosphorus are the major non-neurologic factors which contribute to respiratory muscle fatigue and failure. Respiratory muscle fatigue has two components. High frequency fatigue occurs rapidly with intense contractile efforts but is usually not severe. It also recovers rapidly with rest. Low frequency fatigue develops more slowly but is severe and requires hours for recovery. Since the spontaneous rate of neural stimulation is predominantly in the low frequency range, this component of fatigue is of particular clinical importance. Fatigue of the inspiratory muscles leads to acute respiratory acidosis, but before carbon dioxide retention occurs, it can be recognized from characteristic symptoms and signs. These include dyspnea which responds to mechanical ventilation, rapid shallow breathing, and asynchronous movements of the chest and abdomen. Inspiratory muscle fatigue must be treated by putting these muscles to rest, by mechanically supporting ventilation. In addition, underlying metabolic nutritional and circulatory abnormalities must be corrected and infection treated. Aminophylline and isoproterenol can restore inspiratory muscle contractility, but controlled clinical trials remain to be done regarding their application in acute and chronic respiratory failure. Inspiratory muscle training improves strength and endurance in patients with obstructive lung disease, cystic fibrosis, and spinal cord injury, but does not always improve physical exercise performance. Again, more work is needed to develop the indications for inspiratory muscle training and to determine the optimum type and duration of the training regimen.
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PMID:Respiratory muscle failure. 634 27

The effects of aminophylline on diaphragmatic fatigue and recovery in the face of hypoxemia and hypercapnic acidosis were studied in anesthetized, spontaneously breathing, dogs. The phrenic nerves were stimulated supramaximally at 10, 20, 50, and 100 Hz during 2 s with electrodes placed around the fifth roots, and the resulting transdiaphragmatic pressure (Pdi) was measured with balloon catheters. The dogs were occluded before the stimulations at functional residual capacity. The latter was monitored by measuring the end-expiratory transpulmonary pressure, which remained constant throughout the experiment. Diaphragmatic fatigue was produced by resistive loaded breathing. At the end of the runs, which lasted 15 +/- 2 min, all the dogs were severely hypoxemic (30 +/- 5 mmHg), hypercapnic (65 +/- 4 mmHg), and acidotic (7.1 +/- 0.05). During the fatigue runs, phrenic stimulation resulted in a marked decrease in Pdi, which amounted at 20 Hz to 70 +/- 8% and 45 +/- 12% of the control values 5 min after the onset of the fatigue runs and at the end, respectively. After recovery (3 h), Pdi and arterial blood gas determinations returned to control values. Identical fatigue runs were repeated with aminophylline infusion (loading dose, 6 mg/kg in 10 min and maintenance dose, 1 mg/kg/h), leading to a plasmatic concentration of 16.4 +/- 2 mg/l. Aminophylline protected the diaphragm against fatigue, and despite the presence of hypoxemia and hypercapnic acidosis, the Pdi generated for a 20 Hz stimulation of the phrenic nerves at identical times of the preceding run amounting to 100 +/- 15% and 85 +/- 10% of control values, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of aminophylline on diaphragmatic fatigue during acute respiratory failure. 642 14

1. The effect of intravenous aminophylline on the contractility of adductor pollicis has been studied in three subjects both in the fresh state and following the induction of muscle fatigue. 2. Aminophylline had no influence on the frequency-force relationship and relaxation rate of adductor pollicis in the fresh state. 3. Fatigue resulted in a selective depression of the force response to low and moderate frequencies of stimulation and a slight effect on maximum force production 10 and 35 min afterwards. 4. Aminophylline given prior to, during and/or after fatigue did not influence this selective low-frequency fatigue at 10 or 35 min. 5. Aminophylline at the concentrations obtained has no significant effect on muscle contractility or fatiguability in man.
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PMID:Aminophylline and fatigue of adductor pollicis in man. 683 38

In an attempt to explain the clinical efficacy of aminophylline, we studied its effect on diaphragmatic function in eight normal subjects. The relation between the electrical activity of the diaphragm and the pressure generated by the diaphragm was assessed during voluntary contractions before and after aminophylline infusion. Aminophylline shifted the electrical activity/pressure curve to the left; the pressure at a given electrical activity increased an average of 15 per cent (P less than 0.001). In four subjects, pressure was also measured during stimulation of the phrenic nerve at various frequencies before and after diaphragmatic fatigue was produced by resistive breathing, with and without aminophylline infusion. Pressure increased after fatigue at all stimulation frequencies with aminophylline, as compared with the pressure after identical fatigue runs at the same stimulation frequencies without aminophylline. The mean plasma aminophylline concentration associated with these responses was 13 +/- 0.9 mg per liter. We conclude that aminophylline improves the diaphragm's contractility and renders it less susceptible to fatigue.
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PMID:Aminophylline improves diaphragmatic contractility. 724 14

The clinical relevance of methylxanthines as therapeutic agents for improving diaphragmatic contractility is controversial. In a double-blind, placebo-controlled trial, we investigated the effect of aminophylline on the contractility of fresh and fatigued human diaphragm at different lung volumes, and therefore as a function of fiber length. The diaphragmatic contractility of normal subjects was assessed by measurements of transdiaphragmatic pressure changes (Pdi,T) in response to single, bilateral, supramaximal phrenic-nerve shocks during relaxation from total lung capacity (TLC) to functional residual capacity (FRC). Fatigue was induced by resistive breathing. Therapeutic levels of theophylline were reached in all subjects. Under fresh (i.e., nonfatigue) conditions, aminophylline significantly increased Pdi,T at lung volumes above 75% of the inspiratory capacity (IC). Fatigue in the absence of aminophylline caused a disproportionately greater reduction of Pdi,T at high than at low lung volume (J. Appl. Physiol. 1992; 72:1064), which was rapidly reversible with rest. With aminophylline, the disproportionate decrease in diaphragmatic contractility at short fiber lengths was not observed. Aminophylline potentiates diaphragmatic contractility to a proportionately greater extent at short than at long fiber lengths, under both fresh and fatigued conditions. We explain these findings by known effects of muscle shortening, fatigue, and methylxanthines on excitation-contraction coupling mechanisms.
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PMID:Effects of fatigue, fiber length, and aminophylline on human diaphragm contractility. 759 25


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