Abstract 1900 Neonatal Disease Oriented Research: Steroids & Oxygen: Perinatal Effects Poster Symposium, Sunday, 5/2

Lung hypoplasia with abnormal alveolarization contributes to the morbidity and mortality of several neonatal lung diseases associated with pulmonary hypertension, such as bronchopulmonary dysplasia, congenital diaphragmatic hernia and primary lung hypoplasia. Past studies have shown that perinatal hypoxia decreases alveolar number in young rats. In this study, we hypothesized that abnormal lung development caused by brief perinatal hypoxia will predispose rats for a higher risk to develop pulmonary hypertension when re-exposed to hypoxia later in infancy. Pregnant rats were put into a hypobaric chamber (FiO2 = 0.10) 3 days before delivery. After birth, mothers and newborns were kept in hypoxia for an additional 3 days. Control rats were born and raised in room air. At 2 weeks of age, both groups were either exposed to 10% O2 for one week or kept in room air. Rats were studied at 2 and 3 weeks of age. Alveolarization was measured by radial alveolar counts (RAC), and pulmonary vessel density was determined by counting vessel number per high power field after immunostaining for Factor VIII-related antigen. Hematocrit (Hct) and right ventricular hypertrophy (expressed as the ratio of right ventricle (RV) to left ventricle plus septum (LV+S) weights; RV/LV+S) were also measured. Rats exposed to perinatal hypoxia had higher RV/LV+S (0.45±0.01 vs. 0.37±0.01; p<0.05) and Hct (40±1% vs. 32±1%; p<0.05) and decreased RAC (8±1 vs. 10±1; p<0.05) at 2 weeks of age. After re-exposure to hypoxia for one week, the perinatal hypoxia rats developed a greater increase in RV/LV+S (0.51±0.02 vs. 0.38±0.01; p<0.05) and Hct (63±1% vs. 52±2%; p<0.05), a decrease in pulmonary vessel density (15±1 vs. 22±1 vessels per high power field; p<0.05) and an increased ratio of RAC to vessel density (0.58±0.03 vs. 0.45±0.02; p<0.05), in comparison with controls. We conclude that brief perinatal hypoxia rendered infant rats more susceptible to pulmonary hypertension, despite a recovery period in normoxia. We speculate that disrupted alveolarization and abnormal vascular growth following perinatal hypoxia may play an important role in increasing the severity of pulmonary hypertension when re-exposed to hypoxia later in infancy.