Prenatal dexamethasone administration to premature rats exposed to prolonged hyperoxia: A new rat model of pulmonary fibrosis (bronchopulmonary dysplasia)

Objective: To evaluate the postnatal effects of prenatal dexamethasone treatment of preterm rats and to test the hypothesis that prenatal dexamethasone treatment protects against pulmonary oxygen toxicity in the preterm rats and stimulates lung antioxidant enzyme levels in response to hyperoxia. Study design: We administered dexamethasone (0.4 mg/kg, intraperitoneally), or equivolume saline solution to pregnant rats at 48 and 24 hours before premature delivery at gestation day 21. Both groups of prematurely delivered rat pups were randomly assigned to either >95% O-2 or room air immediately after birth and brief resuscitation. Results: The hyperoxic survival rates from day 1 through day 14 were similar in both dexamethasone-treated and control preterm O-2 groups. At 7 days of hyperoxia, the preterm pups demonstrated similar lung antioxidant enzyme activity and surfactant content responses to high O-2 in the dexamethasone-treated and control groups, Lung quantitative morphometry changes were similar (equal degree of inhibition of normal alveolar development) in both groups. Unexpectedly, the lungs of the preterm O-2 control rats showed evidence of septal fibrosis and the pups that received dexamethasone-O-2 showed even greater severity of septal fibrosis and a greater increase (+50%) of lung hydroxyproline compared with the O-2 group control rats. Conclusions: In preterm animals, prenatal dexamethasone administration does not show any of the hypothesized protective effects against hyperoxia or protective biochemical lung changes during prolonged O-2 exposure, However, prenatal dexamethasone administration with prolonged exposure of the preterm rat to hyperoxia results in a pulmonary pathologic picture quite similar to bronchopulmonary dysplasia.