Prenatal hypoxia preconditioning improves hypoxic ventilatory response and reduces mortality in neonatal rats

Objective: Severe hypoxia/ischemia is a major cause of neonatal cardiorespiratory dysfunction and mortality. We tested whether prenatal hypoxia preconditioning would augment hypoxic and hypercapnic ventilatory responses, and thereby reduce neonatal mortality. Methods: Pregnant rats at 19 days' gestation were exposed to six episodes of intermittent hypoxia (10-min of 15% O-2 followed by 10-min of normoxia/episode, PPC), or room air (CON) per day until delivery. The ventilatory responses to 1 min of 10% O-2 and 10% CO2, and 5 min of 5% O-2 were performed in anesthetized pups. The conscious pups were exposed to 5% 02 for 105 min, and their mortality and dry/wet weight of the lung and brain were evaluated. Results: We found that augmented ventilatory responses to 1 min of 10% 02 and 10% CO2 were similar in the two groups (P>0.05). In contrast, 5 min of 5% 02 initially caused a ventilatory peak response followed by a decline that was markedly diminished (35%, P=0.013) by PPC. PPG also significantly decreased neonatal mortality by 22% (P=0.044) as compared with CON. Conclusion: We conclude that prenatal hypoxia preconditioning reduces neonatal mortality apparently by improving the severe hypoxic ventilatory response.