Effects of adenosine and xanthine derivatives on breathing during acute hypoxia in the anesthetized newborn piglet.

Neonates of animals and humans exhibit a paradoxical ventilatory response to hypoxia characterized by an initial increase in minute ventilation followed by a late, sustained decrease. Exogenous adenosine analogues cause respiratory depression, and the xanthine derivative aminophylline, a competitive inhibitor of adenosine receptors, decreases the amount of hypoxic ventilatory depression in the newborn piglet. Other xanthine derivative such as enprofylline are weak adenosine antagonists. The purpose of this report is to test the hypothesis that enprofylline would not reverse ventilatory depression caused by hypoxia, supporting the suggestion that adenosine contributes to hypoxic ventilatory depression. To confirm the weak adenosine antagonism of enprofylline, L-N6-(phenylisopropyl)adenosine (PIA) was administered to six newborn piglets until respiratory depression was achieved. Either aminophylline or enprofylline was then administered. Aminophylline, but not enprofylline, reversed the respiratory depression caused by PIA. In seven additional piglets, respiratory depression was first produced by 10% oxygen breathing and the ability of saline, aminophylline, and enprofylline to reverse the decrease in ventilation was evaluated. The administration of either saline or enprofylline produced little change in minute ventilation (9.8% +/- 3.7% and -11.7% +/- 7.7%, respectively), whereas aminophylline consistently produced an increase (43.5% +/- 7.3% [P less than 0.001]). Both aminophylline and enprofylline increased heart rate (P less than 0.01), whereas saline produced no significant change. Blood pressure was increased by enprofylline but not by aminophylline or saline. These findings suggest that, in the anesthetized newborn piglet, adenosine contributes to ventilatory depression caused by hypoxia.