Aminophylline partially blocks ventilatory depression with hypoxia in the awake cat

In humans and cats, the ventilatory response to 30 min of moderate hypoxia is biphasic, an initial increase being followed by a decrease in ventilation to levels that are often less than halfway between the initial response and the air-breathing control level. The decrease, or hypoxic depression, is thought to be of central origin. In humans, intravenous aminophylline, an adenosine blocker, blunts hypoxic depression and may completely block it in anesthetized cats. We studied 11 adult cats while awake, measuring ventilation and end-tidal Po2 (Peto2) and Pco2 (Petco2) during 30 min of isocapnic hypoxia (Petco2 32 Torr (1 Torr = 133.3 Pa), Peto2 60 Torr) after intravenous aminophylline on 1 day and saline on another. On the saline day hypoxia initially produced a 75% increase in ventilation, which declined at 30 min to 110% of control, largely owing to a decrease in tidal volume. With aminophylline, room-air ventilation was slightly increased, and hypoxia initially produced a 50% increase in ventilation, which then declined to 130% of control at 30 min. Late in hypoxia, ventilation was significantly greater with aminophylline than with saline. The degree of hypoxic depression was not related to blood theophylline levels and was similar after aminophylline doses of 10 and 13 mg/kg. We conclude that hypoxic depression is at least partially due to adenosine accumulation, the effect of aminophylline being likely due to central adenosine blockade.