Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001127 (respiratory acidosis)
 1,501 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Hypoxia or hypercapnia impairs diaphragmatic contractility and induces fatigue. However, little is known about the combined effect of hypoxic and hypercapnic acidosis (HHA) on diaphragmatic fatigue. In this study, a gas mixture (21% O2, 12% CO2 and 67% N2) was used to produce HHA-induced rat diaphragmatic fatigue. Force-frequency relationships and twitch characteristics including peak twitch tension (PTT), time to peak tension (TPT), half relaxation time (1/2RT), maintaining tension (MT) and direct-muscle-stimulation tension (MST) were measured in diaphragm preparations from male SD rats. The HHA gas mixture attenuated force at all frequencies (5-120 Hz) and decreased PTT, MT and MST significantly. Aminophylline, a positive control drug, blocked the negative inotropic effect of HHA in a dose-dependent manner. Moreover, salmeterol, a long-acting beta2-adrenoceptor agonist, inhibited the harmful effect of HHA at high frequencies (40-120 Hz), but without effect on MT and MST. These results suggest that an in vitro HHA-induced rat diaphragmatic fatigue model could be established by aerating with the gas mixture, which may be an optimal model to screen effective drugs for diaphragmatic fatigue. Furthermore, salmeterol may play a protective role in HHA-induced impairment.
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PMID:An in vitro rat diaphragmatic fatigue model induced by combined hypoxic and hypercapnic acidosis and the effect of salmeterol. 1631 Mar 75