110 - Serial echocardiogram assessments of pulmonary hemodynamics and right ventricular hypertrophy in infant rats with experimental bronchopulmonary dysplasia due to antenatal endotoxin.

Poster Number: 110
Publication Number: 110.1936

Background: Pulmonary hypertension (PH) and related pulmonary vascular disease (PVD) in premature infants present profound challenges, including its pathogenesis and non-invasive characterization by echocardiogram (echo).

Objective: We sought to define serial changes in echo metrics of PH that best characterize the presence and progression of cardiopulmonary disease in a well-established rodent model of bronchopulmonary dysplasia and pulmonary hypertension (BPD-PH) induced by chorioamnionitis, which is characterized by reduced alveolarization and pulmonary vessel density and development of right ventricular hypertrophy (RVH) from birth to 14 days of age.

Design/Methods: Endotoxin (ETX, 10ug/sac) was administered to pregnant rats by intra-amniotic (IA) injection at embryonic day 20 (E20; term = E22) and pups were delivered by cesarean-section at E22. Transthoracic 2D and Doppler imaging were performed in spontaneously breathing rats using a VisualSonics Vevo 1100 ultrasound system. To quantify septal flattening, left ventricular eccentricity index (LV EI) at the end of systole was assessed at days 2, 4, 7, and 14. Pulmonary artery acceleration time (PAAT), pulmonary artery ejection time (PAET), PAAT adjusted by PAET (PAAT/PAET), and end-diastolic right ventricular wall thickness (RVWTd), were assessed at days 7 and 14. T-tests were performed for statistical significance.

Results: In comparison with the CTL group, the ETX group demonstrated an increase in LV EI at days 2, 4, 7, and 14 (p < 0.05). There were no significant differences in PAAT, PAET, PAAT/PAET, and RVWTd at day 7. At day 14, compared to CTL, ETX demonstrated an increase in PAET by 17.4 % (p < 0.01), RVWTd by 34.7% (p < 0.05), and a decrease in PAAT/PET ratio by 15.1% (p < 0.01). However, PAAT measurements were not different between study groups at day 14.

Conclusion(s): Antenatal ETX exposure increased echo metrics of PH in infant rats during the first 2 postnatal weeks. Early changes in LV EI were statistically significant at days 2, 4, 7, and 14. PAAT/PAET, and RVWTd were different at day 14, but not at day 7, suggesting progression of disease. We speculate that echo is a valuable noninvasive tool to longitudinally study mechanisms underlying the temporal progression of cardiopulmonary disease and to phenotype pulmonary hemodynamics in experimental BPD-PH. These findings further suggest that LV EI precedes the increase in RVWT and may provide an early marker for PH among other traditional echo measurements and can characterize early changes to RV pressure load due to PVD in infant rats after antenatal inflammation.