Postnatal development of eupneic ventilation and metabolism in rats chronically exposed to moderate hyperoxia

Abstract

Newborn rats chronically exposed to moderate hyperoxia (60% O2) exhibit abnormal respiratory control, including decreased eupneic ventilation. To further characterize this plasticity and explore its proximate mechanisms, rats were exposed to either 21% O2 (Control) or 60% O2 (Hyperoxia) from birth until studied at 3–14 days of age (P3–P14). Normoxic ventilation was reduced in Hyperoxia rats when studied at P3, P4, and P6–7 and this was reflected in diminished arterial O2 saturations; eupneic ventilation spontaneously recovered by P13–14 despite continuous hyperoxia, or within 24h when Hyperoxia rats were returned to room air. Normoxic metabolism was also reduced in Hyperoxia rats but could be increased by raising inspired O2 levels (to 60% O2) or by uncoupling oxidative phosphorylation within the mitochondrion (2,4-dinitrophenol). In contrast, moderate increases in inspired O2 had no effect on sustained ventilation which indicates that hypoventilation can be dissociated from hypometabolism. The ventilatory response to abrupt O2 inhalation was diminished in Hyperoxia rats at P4 and P6–7, consistent with smaller contributions of peripheral chemoreceptors to eupneic ventilation at these ages. Finally, the spontaneous respiratory rhythm generated in isolated brainstem-spinal cord preparations was significantly slower and more variable in P3–4 Hyperoxia rats than in age-matched Controls. We conclude that developmental hyperoxia impairs both peripheral and central components of eupneic ventilatory drive. Although developmental hyperoxia diminishes metabolism as well, this appears to be a regulated hypometabolism and contributes little to the observed changes in ventilation.