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% CO(2), and 5 min of 5% O(2) were performed in anesthetized pups. The conscious pups were exposed to 5% O(2) for approximately 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% O(2) and 10% CO(2) were similar in the two groups (P>0.05). In contrast, 5 min of 5% O(2) initially caused a ventilatory peak response followed by a decline that was markedly diminished (35%, P=0.013) by PPC. PPC 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.