421 - Antenatal Betamethasone Preserves Lung Structure and Function and Prevents Pulmonary Hypertension in Rat Model of Chorioamnionitis-Induced Bronchopulmonary Dysplasia

Poster Number: 421
Publication Number: 421.429

Adom Netsanet, University of Colorado School of Medicine, Aurora, CO, United States; Steven Abman, University of Colorado School of Medicine, denver, CO, United States; Gregory J. Seedorf, University of Colorado School of Medicine, Aurora, CO, United States

Background: Bronchopulmonary dysplasia (BPD), the chronic lung disease of preterm birth, is characterized by arrested lung development, abnormal lung function, and increased risk for pulmonary hypertension (PH). Clinical studies have shown strong associations of antenatal inflammation from chorioamnionitis (CA) with high risk for developing BPD. Administering endotoxin (ETX) into the amniotic space mimics CA by impairing infant lung growth and causing pulmonary hypertension (PH). Antenatal steroids improve many complications of prematurity; however, it remains uncertain whether they reduce markers for BPD in the setting of antenatal inflammation.

Objective: The objective of this study is to assess the impact of antenatal betamethasone administration in the setting of experimental CA on postnatal lung structure and function in preterm rat pups by measuring molecular and whole-animal endpoints. We hypothesize that antenatal betamethasone administration will help preserve lung alveolar and vascular growth and reduce the PH in a rat model of CA-induced BPD.

Design/Methods: Intra-amniotic endotoxin (ETX; 10 μg/sac) or saline (CTL; 50ul/sac) was administered to rat pups via laparotomy of pregnant dams at embryonic day 20 (E20; term, 22 days). Betamethasone (BM; 0.2mg/kg) was administered via intramuscular injection to dams at E20. Pups were delivered by cesarean section at E22. Four subgroups were identified: saline (control), ETX, BM, and ETX+BM. Functional and morphometric analyses were performed at 2 weeks of age. Study endpoints included lung mechanics (total lung resistance and compliance); alveolar number by radial alveolar counts (RAC); vessel density; and right ventricular hypertrophy (RVH) (right ventricle/left ventricle+septum weights x 100).

Results: In comparison with controls, antenatal ETX impaired lung growth, increased lung resistance, reduced compliance, and increased RVH at DOL14. Maternal BM treatment of ETX exposed fetal rats preserved distal lung structure and function and prevented RVH. BM treatment reduced total lung resistance by 15.3% and improved compliance by 9.5% (p < 0.05). BM also preserved lung complexity as measured by alveolar growth as determined by radial alveolar counts (RAC; (p < 0.05), increased vessel density and improved RVH by 42.3% (p < 0.05).Conclusion(s): Antenatal betamethasone administration preserves lung growth and structure, restores lung function, and prevents RVH in this model of BPD. We speculate that in the subgroup of pregnancies complicated by CA, antenatal steroids can reduce the risk for BPD.
CV_Adom Netsanet_August 2021CV_Adom Netsanet_August 2021.pdf