Effect of theophylline on ventilatory roll-off during hypoxia in goats

The increase in pulmonary ventilation (VE) during the first minutes of hypoxia is not sustained as after several minutes VE decreases or "rolls-off" toward control levels. We hypothesized that intravenous infusion of theophylline, by blocking the central inhibitory effects on breathing of adenosine, would attenuate the hypoxic VE roll-off. Twelve unanesthetized adult goats were exposed for 20 min to a 12% O2-88% N2 gas mixture. In some studies,theophylline was infused intravenously (IV) for 20 min before and during the hypoxia. The highest infusion rate of 6.0--8.0 mg/min was sufficient to totally prevent the arterial hypertension and bradycardia that occurred with IV infusion of 4 mg min (-1) of adenosine. Nine of the 12 goats demonstrated VE roll-off without the theophylline infusion. In goats that demonstrated VE roll-off without theophylline, a significant (P < 0.05) VE roll-off was observed even at the highest theophylline infusion rate. We therefore conclude that the VE roll-off during hypoxia is not primarily or critically mediated by adenosine in awake, adult goats.