Abstract 1824 Neonatal Disease Oriented Research: Steroids & Oxygen: Perinatal Effects Poster Symposium, Sunday, 5/2

Alveolar simplification and lung hypoplasia contributes to several neonatal lung diseases, including bronchopulmonary dysplasia, congenital diaphragmatic hernia and lung hypoplasia. These diseases are also associated with an increased risk for development of pulmonary hypertension (PH). In the rat lung, postnatal development includes a phase of postnatal alveolarization from day 3 through 21, which can be disrupted by dexamethasone (Dex) treatment. Whether Dex-induced lung hypoplasia increases the risk for development of PH is unknown. To determine if lung hypoplasia increases the risk for the development of PH in adult rats we inhibited alveolarization in newborn Sprague Dawley rats by performing Dex injections (0.25ug/day) for 11 days (days 3-13). Litters were divided equally between Dex-treated and vehicle controls (ethanol, 20ul/day). Rats were either raised at Denver's altitude until 10 weeks of age (Normoxic groups), or at Denver's altitude until 7 weeks of age and then placed in a hypoxia chamber (FiO2=0.10; Hypoxic groups) for 3 weeks to induce PH. Lungs were formalin-fixed at constant pressure (10 cm water). Right ventricle (RV) and left ventricle plus septum (LV+S) weights were measured to determine right ventricular hypertrophy (RVH; RVH=RV/LV+S). Lung hypoplasia and alveolar simplification was evident at 10 weeks in the Dex-treated groups. RVH was not present in the Dex normoxic group, but the RV/LV+S was increased in the Dex hypoxic group compared to controls (0.66±0.03 vs. 0.50±0.04; p<0.05). We conclude that early Dex treatment increases the risk for severe PH after exposure to hypoxia in adult rats. (Figure)

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