AMINOPHYLLINE REDUCES HYPOXIC VENTILATORY DEPRESSION - POSSIBLE ROLE OF ADENOSINE

Newborn infants and animals typically exhibit a paradoxical ventilatory response to hypoxia. The depressive phase of the response was not adequately explained. Hypoxia may cause the release of inhibitory neuromodulators which depress ventilation. The nucleoside, adenosine, may be involved because it is rapidly released during hypoxia, it depresses ventilation, and theophylline, a competitive inhibitor, was successfully used to treat apnea of prematurity. The effects of aminophylline on ventilation during hypoxia in the spontaneously breathing newborn piglet administered both rapidly after ventilatory depression occurred (bolus) and before the onset of hypoxia (pretreatment) are described. Ten percent O2 breathing produced a typical biphasic ventilatory response. The decrease in minute ventilation was caused by a decrease in both tidal volume and respiratory frequency. The bolus administration of aminophylline reversed the depression in minute ventilation (P < 0.001) by increasing tidal volume (P < 0.002). Pretreatment with aminophylline decreased the amount of ventilatory depression (P < 0.05) by preventing a decrease in respiratory frequency. Aminophylline, an adenosine antagonist, reduces the decrease in ventilation which occurs during hypoxia in the newborn. Adenosine may play a role in hypoxic ventilatory depression and respiratory control in the newborn.