Effect of theophylline on respiratory neuromuscular drive

To investigate the possible mechanisms by which theophylline affects the control of ventilation, neuromuscular drive and ventilatory function were examined in 7 healthy men receiving an incremental intravenous aminophylline dosing schedule to achieve plasma theophylline concentrations of 5, 10, and 15 micrograms/ml. As compared with the baseline (predose) values, the 3 incremental aminophylline doses significantly (p less than 0.05 to 0.01) increased occlusion pressure (P0.1) and maximum inspiratory pressure static (MIPS) at functional residual capacity (FRC). This was not observed for ventilatory flow (V), tidal volume (VT), inspiratory time to total breathing cycle time ratio (Ti/Ttot) VT/Ti, and effective impedance [P0.1/VT/Ti)]. When maximum electrical activity of diaphragm (Edimax) and transdiaphragmatic pressure (Pdimax) were examined in 3 of the 7 subjects, Pdi/Edi tended to increase with increasing theophylline concentrations, while Edimax did not. Our results suggest that the increase in P0.1 during the increase in aminophylline dose is caused by an improvement in respiratory muscle contractility, rather than by a central effect or by an increase in neural drive.