Level and duration of developmental hyperoxia influence impairment of hypoxic phrenic responses in rats

Developmental hyperoxia (1-4 wk of 60% O-2) causes long-lasting impairment of hypoxic phrenic responses in rats. We hypothesized that shorter or less severe hyperoxic exposures would produce similar changes. Hypoxic phrenic responses were measured in 3- to 5-mo-old, urethane-anesthetized rats exposed to 60% O-2 for postnatal day 1 or week 1 or to 30% O-2 for postnatal week 1. Whereas 1 day of 60% O-2 had no lasting effects (P > 0.05 vs. control), both 1 wk of 60% O-2 and 1 wk of 30% O-2 decreased adult hypoxic phrenic responses (P < 0.05 vs. control), although the effects of 30% O-2 were smaller. Hypoxic ventilatory responses (expressed as the ratio of minute ventilation to metabolic CO2 production) were also reduced in unanesthetized rats (5-10 mo old) exposed to 1 wk of 60% O-2 during development (P < 0.05). An age-dependent increase toward normal hypoxic phrenic responses was observed in rats exposed to 1 wk of 60% O-2 (P < 0.05), suggesting a degree of spontaneous recovery not observed after 1 mo of 60% O-2. These data indicate that long-lasting effects of developmental hyperoxia depend on the level and duration of hyperoxic exposure.