Isoproterenol and aminophylline improve contractility of fatigued canine diaphragm

We investigated the effects of aminophylline and isoproterenol on diaphragmatic fatigue produced by phrenic stimulation in dogs. With a cast around the abdomen, the diaphragm contracted quasi-isometrically while the thorax was open and the animal was ventilated. We assessed contractility by measuring transdiaphragmatic pressure during supramaximal stimulation of the phrenic nerves at different frequencies and also during spontaneous inspiratory efforts. At doses of 20, 40, and 80 mg/kg, aminophylline significantly improved contractility (p less than 0.01) in a dose-dependent manner during low, but not during high frequency stimulation. The maximal improvement (24%) was observed with 80 mg/kg. With intravenously administered doses of 5 and 10 micrograms/min of isoproterenol, contractility was also significantly enhanced (p less than 0.05) during low frequency stimulation. Maximal improvement (12%) occurred with 5 micrograms/min. Similar results were obtained when spontaneous inspiratory efforts were recorded and transdiaphragmatic pressure was compared at a given diaphragmatic electrical activity before and after administration of each drug. Maximal improvement was 23% with aminophylline and 11% with isoproterenol. Analysis of twitch characteristics revealed that peak tension was increased significantly (p less than 0.025) by both drugs. In addition, isoproterenol caused a marked decrease in the time course of relaxation. We conclude that aminophylline and isoproterenol improve contractility of the fatigued diaphragm by increasing the amplitude of the underlying small twitch. Furthermore, the smaller effect of isoproterenol may be the result of reduced relaxation time of the twitch.