PRENATAL DEXAMETHASONE (DEX) ADMINISTRATION TO PREMATURE RATS EXPOSED TO PROLONGED HYPEROXIA: A NEW RAT MODEL OF PULMONARY FIBROSIS[BRONCHOPULMONARY DYSPLASIA (BPD)]. † 1953

Abstract

Although prenatal DEX treatment is known to improve hyperoxic survival in term newborn rats and to stimulate the responses of the lung antioxidant enzyme (AOE) system to hyperoxia, little is know about the postnatal effects of prenatal DEX on prolonged exposure to hyperoxia in preterm animals. To examine the hypothesis that prenatal DEX treatment would also show protective effects in preterm rats exposed to hyperoxia, we administered DEX(0.4 mg/kg, i.p.), or equivolume saline to pregnant rats at 48 and 24 h prior to premature delivery at gestation d 21 (term=22 d). Both groups of preterm rat pups were randomized to either >95% O2 or room air immediately after birth. The hyperoxic survival rates from d 1 through d 14 turned out to be similar in both DEX- and control-O2 groups. At 7 d of hyperoxia, the preterm pups demonstrated similarly increased lung AOE activity and surfactant content responses to high O2 in the DEX and control groups. Lung quantitative morphometry was changed similarly (equal degree of inhibition of normal alveolar development) in both O2 groups. Unexpectedly, the lungs of preterm control-O2 pups showed evidence of septal fibrosis at 13-14 d in O2, and the DEX-O2 group showed even much greater severity of septal fibrosis and a greater increase of lung hydroxyproline compared with the O2 controls. We conclude that in preterm animals, prenatal DEX administration does not show any of the hypothesized protective effects during prolonged O2 exposure. However, prenatal DEX administration with prolonged exposure of the preterm rat to hyperoxia results in a pulmonary pathologic picture quite similar to BPD. This preterm rat model is a much more practical experimental model than the earlier excellent (but very expensive) baboon/monkey model of BPD. Table