Increased hypoxic ventilatory drive due to administration of aminophylline in normal men

We evaluated the effects of intravenous administration and five days of oral administration of aminophylline on hypoxic and hypercapnic ventilatory drives in seven normal men. Serum levels of theophylline were 13.2 micrograms/ml +/- 1.0 micrograms/ml (mean +/- SD) after intravenous administration of aminophylline and 8.8 micrograms/ml +/- 1.7 micrograms/ml after oral administration of aminophylline. Aminophylline had no effect on the slope of the line for carbon dioxide response or on hypoxic ventilatory drive, measured at resting alveolar carbon dioxide tension (PACO2). Hypoxic ventilatory drive was significantly increased (P < 0.025) after intravenous administration of aminophylline when the PACO2 was raised to the control level before aminophylline. Intravenously administered aminophylline shifted the intercept of the line for carbon dioxide response from 40.7 +/- 2.3 to 32.9 +/- 4.6 mm Hg (P < 0.005) and lowered the resting PACO2 from 38.3 +/- 1.8 to 33.7 +/- 2.1 mm Hg (P < 0.005). Similar but smaller changes were seen after oral administration of aminophylline. There was a significant correlation between end-tidal carbon dioxide tension and the serum level of theophylline (P < 0.001), indicating that aminophylline stimulates ventilation in a dose-dependent fashion. This increase in ventilation is due in part to an increase in hypoxic ventilatory drive.