THE EFFECT OF THEOPHYLLINE ON THE HYPOXIC VENTILATORY RESPONSE IN THE NEWBORN PIGLET: ROLE OF THE VAGUS

We have previously demonstrated that theophylline, an adenosine antagonist, reduces hypoxic ventilatory depression in the newborn piglet. In order to investigate the possibility that the stimulatory effects of theophylline we observed were due to effects on vagal pulmonary receptors, we compared the effect of theophylline on the hypoxic ventilatory response in intact and vagotomized newborn piglets. Five newborn piglets less than 3 days of age were exposed to 10 % oxygen under three experimental conditions: 1) intact; 2) after vagotomy; and 3) vagotomy + theophylline. Each animal was anesthetized with ketamine and xylazine, intubated, and the femoral artery catheterized. The vagi were identified but left intact prior to the onset of the experiments. Recordings of expiratory flow and integrated volume, EKG, and arterial blood pressure were obtained during six minutes of hypoxia first before and then beginning 30 minutes after vagotomy. Theophylline (15 mg/kg) was then administered over 10 minutes and after 30 minutes the experiment was repeated. The effect of hypoxia on minute ventilation in each of the three conditions is shown in the graph. Vagotomy alone had no effect on the hypoxic ventilatory response. The addition of theophylline, however, resulted in a greater increase above baseline after 6 minutes of hypoxia (38.7 +/−17.3 %) compared to vagotomy alone (19.8 +/− 15.0 %)(p<0.02). The difference in ventilation was due to changes in frequency rather than tidal volume. We conclude that vagal afferents do not influence the newborn hypoxic ventilatory response and that the effects of methyl xanthines on hypoxic ventilatory depression are not mediated by the vagus.