Hypoxic stress exacerbates hyperoxia-induced lung injury in a neonatal mouse model of bronchopulmonary dysplasia.

BACKGROUND

Premature infants with lung injury often experience intermittent episodes of hypoxemia.

OBJECTIVE

This study investigates whether intermittent hypoxemia exacerbates oxidative stress and lung injury in neonatal mice in a hyperoxia-induced model of bronchopulmonary dysplasia (BPD).

METHODS

For the BPD model, 3-day-old C57Bl/6J mice were exposed to hyperoxia (65% O(2)) for 4 weeks (O(2) group) or to hyperoxia and intermittent (10 min daily) hypoxia (O(2) + H group). Upon completion of O(2) or O(2) + H exposure, the degree of pulmonary alveolarization and granulocytic infiltration were examined. The severity of oxidative injury in lungs was defined by tissue glutathione and protein carbonyl content. Data were compared to those in naïve mice and mice subjected only to intermittent hypoxia.

RESULTS

Hyperoxia-exposed mice exhibited a dramatic (p < 0.0001) decrease of alveolarization, significantly increased granulocytic infiltration (p < 0.0001) and increased protein carbonyl content (p = 0.04) compared to naïve mice. However, O(2) + H mice demonstrated significantly (p = 0.03) fewer alveoli compared to their O(2) counterparts. This was associated with a significantly (p = 0.02) decreased pulmonary total/oxidized glutathione ratio and a significant (p = 0.03) elevation of protein carbonyl content.

CONCLUSIONS

Thus, intermittent hypoxic stress during hyperoxic induction of BPD in mice potentiates oxidative stress in lung tissue and exacerbates alveolar developmental arrest.