Maturation of Ventilatory Responses to Hypoxia, Hypercapnia, and Combined Hypoxia and Hypercapnia in Rats. † 1446

Although the neonatal ventilatory responses to hypoxia and hypercapnia are well characterized, their combined effect is less well described and has not been compared during maturation from neonatal to adult life. We therefore sought to characterize the ventilatory responses to hypoxia, hypercapnia, and combined hypoxia and hypercapnia in 9 littermate Sprague-Dawley rats at postnatal ages of 5, 16-17, 22-23, and 41-42 days. All animals were exposed sequentially to 12% O₂ in N₂, 10% CO₂ in room air, and combination of 10% CO₂ and 12% O₂. Ventilation was measured by whole body plethysmography in unanesthetized, unrestrained animals, and tidal volume, frequency and minute ventilation (Ve) were measured during 5 minutes of each exposure. The ventilatory response to hypoxia was biphasic (an initial, transient increase in Ve) at 5 and 16 days, and sustained at 22 and 41 days. However, the magnitude of percentage increase in Ve to hypoxia at five minutes did not differ between ages. Percent change in Ve to 10% CO₂ increased significantly with advancing age (65%±34% at 5 days vs 207%±62% at 41-42 days, p<.0001). The percent increase in Ve to combined hypoxia and hypercapnia was significantly greater than the response to hypercapnia alone at 5 and 22-23 days. We conclude that (1) despite transition from a biphasic to a sustained hypoxic response, magnitude of the percent increase in Ve to hypoxia alone did not change with age; (2) hypercapnic responsiveness markedly increased with maturation; and (3) hypoxia significantly enhanced hypercapnic responsiveness at both 5 and 22 days. From these results we speculate that differential maturation in the ventilatory responses to hypoxia and hypercapnia may be a factor in the greater instability of ventilation in the neonatal period.Figure

Supported by HL56470.