EFFECTS OF AMINOPHYLLINE ON DIAPHRAGMATIC FATIGUE DURING ACUTE RESPIRATORY-FAILURE

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Abstract
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 5th roots, and the resulting transidaphragmatic 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 mm Hg), hypercapnic (65 .+-. 4 mm Hg) 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 per 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. Aminophylline also had a curative action when administered at the end of the fatigue runs, with the Pdi generated after administration of aminophylline (15 mg/kg i.v.) restored to the prefatigue values 25 .+-. 6 min after the injection of the drug. Aminophylline has a potent protective effect on diaphragmatic fatigue in acute respiratory failure that may bear important therapeutic implications.