Central origin of biphasic breathing pattern during hypoxia in newborns.

Abstract

The ventilatory response to moderate hypoxia of both animal and human newborns differs significantly from that of adults. The newborn response is characterized by transient hyperpnea followed by return of ventilation toward or below the control level and even apnea. To determine whether central respiratory control mechanisms are affected by hypoxia in newborns, we used an anesthetized, paralyzed, mechanically ventilated piglet model in which the vagus nerves were cut. Respiratory activity was determined by measuring electrical activity of a cut phrenic nerve. During a 6-min continuous exposure to 15% O2 as the inspired gas, 11 piglets increased their respiratory output to 181 +/- 38% of the control value within 2.5 min. However, by the 6th min the average respiratory output had declined to 104 +/- 25% of the control. During the exposure to hypoxia, the servo-controlled ventilator frequency (an index of CO2 flux to the lungs) was persistently greater than control (28.0 +/- 1.0 vs. 30.5 +/- 1.4 cycles/min; P less than 0.01). These data indicate that the newborn's characteristic breathing response to hypoxia is due to failure of central neural respiratory control mechanisms. Paralysis, constant end-tidal PCO2, and increased ventilator rate during hypoxia exclude changes in pulmonary mechanics or decreased metabolic rate as explanations of the paradoxical decline in respiratory output.