O2107: Development of Late Pulmonary Hypertension After Antenatal Inflammation in Experimental Bronchopulmonary Dysplasia

Background: Antenatal inflammation due to chorioamnionitis is strongly associated with the development of bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension (BPD-PH) after preterm birth. However, mechanisms linking antenatal stress with temporal changes in the pulmonary circulation leading to BPD-PH during infancy are incompletely understood. We hypothesized that antenatal inflammation impairs lung alveolar and vascular growth that precedes and increases susceptibility for the development of late BPD-PH.

Methods: Fetal rats received intra-amniotic ETX or saline 2 days before term delivery. We quantified temporal changes in lung structure, mechanics, and pulmonary hemodynamics by echocardiogram at postnatal days 2 (P2), P7, and P14.

Results: ETX-exposed rats exhibited significantly reduced radial alveolar counts (RAC) by 27% at P2 and P7, and by 43% at D14 compared to controls (p < 0.05). Pulmonary vascular density decreased by 31.5% at P2, 46.2% at P7, and 38.6% at P14 (p < 0.05) in the ETX-exposed groups compared to controls. ETX-exposed rats showed progressive arterial wall thickening, with vessel wall thickness increasing by 48.5% at P7 and 85.5% at P14 (p < 0.05).
Serial echocardiograms revealed increased interventricular septal flattening at P2 by 25.2%, at P7 by 35.1%, and by 48.1% at P14 in the ETX group compared to controls. At P7, EXT-exposed pups showed increased right ventricular wall thickness in diastole (RVWTd) by 20.7% compared to controls. At P14, ETX-exposed pups show an increase in RVWTd by 19.3%, a decrease in pulmonary artery acceleration time to ejection time ratio by 17.8%, and an increase in right ventricular systolic to diastolic duration ratio by 7.9% (p < 0.05).

Conclusion: Antenatal inflammation impairs lung vascular growth shortly after birth and causes early pulmonary vascular disease, which precedes sequential changes in pulmonary artery remodeling and echocardiogram markers of PH during the postnatal period, even in the absence of postnatal injury.