CHRONIC MODIFICATIONS OF LUNG AND HEART DEVELOPMENT IN GLUCOCORTICOID-TREATED NEWBORN RATS EXPOSED TO HYPEROXIA OR ROOM AIR

We assessed the mechanics and morphology of the lung in 165 rats treat ed neonatally with either room air (RA), O2, RA + steroids, or O2 + st eroids. Newborn Sprague-Dawley male rats were randomly assigned to the se groups, O2-exposure (0.96-1.0 Fi(O2)) lasted 5 days, and dexamethas one treatment consisted of eight daily S.C. injections of drug or buff er in successive doses of 0.5, 0.4, 0.3, 0.2, 0.1, 0.1, 0.1, and 0.1 m g/kg. At 58 days, right ventricular systolic pressure (RVP) was measur ed. At 60 days, all rats were sacrificed for obtaining lung weight and DNA, saline pressure-volume (P-V) curves, and morphometry. We weighed right ventricles (RV) and left ventricles + septa (LV). Hyperoxia alo ne did not, but steroid decreased survival rate to 79.4%(95.3% in RA r ats, P < 0.02). Only 21 of 40 (52%) O2 + steroids rats survived, less than in both RA groups (P < 0.001). RV weight, RVP and muscularization of alveolar duct arteries were significantly increased in O2 vs. RA r ats. In RA + steroids rats, weight of the LV was decreased but RV, RVP , and lung vasculature were not affected. These effects were additive in the O2 + steroid group. Wet lung weights and DNA were increased for RA + steroid rats over all others. O2 and steroids shifted the P-V cu rve to the left and O2 + steroids still further. Maximal lung volume i ncreased significantly with RA + steroids and still further in O2 + st eroids but not in O2 alone. O2 and steroids significantly increased th e mean linear intercept and O2 + steroids even more so. In O2- and ste roid-treated rats, the parenchymal air space increased. In conclusion, both neonatal hyperoxia and steroid administration caused aberrations in the growth of lung and connective tissue. The effects of the two w ere additive. The vascular system, maximal lung volume, and DNA respon ded differently, presumably by different modes of action. (C) 1993 Wil ey-Liss, Inc.