Critical developmental period for hyperoxia-induced blunting of hypoxic phrenic responses in rats

Hypoxic ventilatory and phrenic responses are reduced in adult rats reared in hyperoxia (60% O(2)) for the first month of life but not after hyperoxia as adults. In this study, we identified the developmental window for susceptibility to hyperoxia. Phrenic nerve responses to hypoxia were recorded in anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats (aged 3-4 mo) exposed to 60% O(2) for the first, second, third, or fourth postnatal week. Responses were compared with control rats and with rats exposed to 60% O(2) for the first month of life. Phrenic minute activity (burst amplitude x frequency) increased less during isocapnic hypoxia (arterial PO(2) = 60, 50, and 40 Torr) in rats exposed to hyperoxia for the first or second week, or the first month, of life (P < 0.01 vs. control). Functional impairment caused by 1 wk of hyperoxia diminished with increasing age of exposure (P = 0.005). Adult hypoxic phrenic responses are impaired by 1 wk of hyperoxia during the first and second postnatal weeks in rats, indicating a developmental window coincident with carotid chemoreceptor maturation.