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 µg/ml. As compared with the baseline (predose) values, the 3 incremental aminophylline doses significantly (p<0.05 to 0.01) increased occlusion pressure (P_0.1) and maximum inspiratory pressure static (MIPS) at functional residual capacity (FRC). This was not observed for ventilatory flow \((\dot V)\) , tidal volume (V_T), inspiratory time to total breathing cycle time ratio (T_i/T_tot), V_T/T_i, and effective impedance [P_0.1/(V_T/T_i)]. When maximum electrical activity of diaphragm (Edi_max) and transdiaphragmatic pressure (Pdi_max) were examined in 3 of the 7 subjects, Pdi/Edi tended to increase with increasing theophylline concentrations, while Edi_max did not. Our results suggest that the increase in P_0.1 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.