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

Newborn rats chronically exposed to moderate hyperoxia (60% O-2) exhibit abnormal respiratory control, including decreased eupneic ventilation. To further characterize this plasticity and explore its proximate mechanisms, rats were exposed to either 21% O-2 (Control) or 60% O-2 (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 O-2 saturations; eupneic ventilation spontaneously recovered by P13-14 despite continuous hyperoxia, or within 24 h when Hyperoxia rats were returned to room air. Normoxic metabolism was also reduced in Hyperoxia rats but could be increased by raising inspired O-2 levels (to 60% O-2) or by uncoupling oxidative phosphorylation within the mito chondrion (2,4-dinitrophenol). In contrast, moderate increases in inspired O-2 had no effect on sustained ventilation which indicates that hypoventilation can be dissociated from hypometabolism. The ventilatory response to abrupt O-2 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. (C) 2014 Elsevier B.V. All rights reserved.