Respiratory control during hypoxia in newborn rabbits: implied action of endorphins

The mechanism of ventilatory depression during hypoxia in the neonate is unknown. Since endorphins depress ventilation and their actions are antagonized by naloxone, we tested the effect of naloxone on respiration during acute hypoxia in newborn rabbits. In 27 tracheotomized unanesthetized pups, ranging in age from 1 to 15 days, ventilation (VE) was measured in a body plethysmograph. At all ages, inhalation of 5% O2 initially increased VE; thereafter VE became depressed in association with a decrease in CO2 elimination (VCO2). The time constant of VE depression increased with age. During ventilatory and VCO2 depression, saline infusion had no effect. Infusion of naloxone (4 micrograms/g body wt), however, abruptly stimulated both VE and VCO2. Since naloxone acts by competitive blockade of opiate (endorphin) receptors, these data provide evidence that 1) depression in respiration and metabolism during hypoxia is related to the action of endorphins, 2) the degree of endorphin influence decreases with age, and 3) naloxone is effective in reversing hypoxic respiratory depression provided apnea is not established.