Chronic aminophylline administration: Effect on diaphragm contractility and fatigue resistance in vitro

The effects of acute and chronic administrations of aminophylline (AM) on diaphragm contractility and fatigue resistance were examined in 42 rats. In acute experiments (n = 22), the animals received an intravenous bolus of either AM (14 mg/kg; n = 11) or saline (n = 11). Serum AM level was determined 30 min after the bolus (17.8 ± 0.8 mg/L, SD). In chronic experiments (n = 20), either AM (n = 10) or saline (n = 10) was infused subcutaneously via an osmotic minipump at a constant pumping rate of 2.5 μl/h. Serum AM level was measured after 2 wk of pump infusion (12.3 ± 2.0 mg/L, SD). For each animal in both acute and chronic experiments, a muscle strip from the right midcostal diaphragm was placed in an in vitro chamber containing Krebs solution and 12 μM/L curare. For the AM-treated group, AM was added to the tissue bath in a concentration similar to that in the serum. No AM was added to the bath for the control group. Forces were measured isometrically during direct muscle stimulation at different frequencies and standardized to muscle weight. Muscle fatigue was induced by repetitive stimulation at 40 pps, delivered in 330-ms trains, with one train presented each second. With either acute or chronic AM administration, a significant increase in diaphragm contractility was observed (p < 0.01). In contrast, AM did not affect the rate of force decline during fatigue run. However, the time required to produce 50% reduction from the initial tension was longer in both AM-treated groups. We conclude that AM improves diaphragm contractility, but not fatigue resistance, and the improvement in diaphragm contractility persists after 2 wk of AM treatment.