1733 THEOPHYLLINE REDUCES HYPOXIC VENTILATORY DEPRESSION WITHOUT NCREASING CATECHOLAMINES

Abstract

Theophylline (T) reduces hypoxic ventilatory depression in newborn pig lets and can enhance the release of catecholamines (CATs) which in turn may stimulate ventilation. To determine if the effect of T on ventilation was due to the release of CATs, we measured plasma CATs and ventilation in two groups of spontaneously breathing newborn piglets <4 days old treated with either T (n=7) or normal saline (NS) (n=6) both during normoxia and hypoxia. The piglets were anesthetized with ketamine and xylazine, intubated and the femoral artery catheterized o Epinephrine (EPI) and norepinephrine (NE) were measured before and 30 minutes after treatment with T (15 mg/kg) or NS. The animals were exposed to 10% oxygen and the CATs remeasured after 5 minutes of hypoxia. Respiratory rate (RR), expiratory flow integrated to minute ventilation (Ve), heart rate and blood pressure were continuously recorded. CATs were assayed by high pressure liquid chromatography with electrochemical detection.

Treatment with T during normoxla was associated with an increase in tidal volume. During hypoxia treatment with T prevented the falI in Ve and RR seen in the NS group. EPI and NE increased during hypoxia but there was no difference between the groups at 5 minutes. In our model the increase in CATs observed during hypoxia was not enhanced by T. This is consistent with the hypothesis that some mechanism other than catecholamine release is responsible for the effect of T in reducing neonatal hypoxic respiratory depression.

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