Abstract 10678: Structural and Functional Changes of the Right Ventricle in Sprague Dawley and Wistar Rat Models of Pulmonary Arterial Hypertension

Abstract

Introduction: Assessment of right ventricle (RV) function and structure are essential to determine the efficacy of new PAH drugs preclinically. This study compared RV function, structure, and hemodynamics in response to monocrotaline (MCT) in Sprague Dawley (SD) and Wistar rats. Methods: SD and Wistar rats (194-243 g) were administered either 0.9% NaCl or MCT (60 mg/kg) on Day 0. On Day 23, RV function and structure were evaluated by echocardiography. On Day 24, RV pressure-volume relations were assessed, and heart and lung weights were collected. Results: MCT treatment resulted in dilated RV hypertrophy in both strains, but the magnitude of changes were different between strains. RV internal diameter during diastole (61%, p=0.0003) and systole (67%, p=0.001), RV end-diastolic (51%, p<0.0001) and systolic (80%, p<0.0001) area were greater in MCT/SD than MCT/Wistar. MCT/SD also showed increased right atrial area (110%, p=0.0002) vs. MCT/Wistar. Due to increased load, MCT/SD tended to develop a thicker RV free wall (22%, p>0.05) than MCT/Wistar. Systolic dysfunction was observed with MCT treatment in both strains; however, the MCT/SD showed a greater decrease in RV fractional area change (-51%, p=0.009) than MCT/Wistar. The tricuspid annular velocity and annular plane systolic excursion were slightly decreased in MCT/SD compared to MCT/Wistar (p=NS). RV catheterization showed similar MCT-induced increases in RV end systolic and diastolic pressures in both strains. However, the decrease in cardiac output was more pronounced in MCT/SD (-30%, p<0.0001) than in MCT/Wistar. Increase in RV weight normalized by tibia length (RV/TL) and Fulton’s Index was observed with MCT treatment; but the degree of hypertrophy was more pronounced in MCT/SD (57% RV/TL and 37% Fulton’s Index) than MCT/Wistar. Conclusions: Our results showed that while similar hemodynamic changes were observed in SD and Wistar rats in response to MCT, the magnitude of dilated RV hypertrophy and systolic impairment was exacerbated in SD vs. Wistar rats.