Abstract 17396: RV Remodeling in Two Animal Models of Pulmonary Arterial Hypertension

Introduction: Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis. By relating ventricular hemodynamics to wall mechanics, we aimed to discriminate the contributions of ventricular geometric remodeling and intrinsic changes in myocardial mechanical properties in two commonly used PAH animal models at end-systole (ES) and end-diastole (ED) to the maintenance of cardiac output during the early compensated phase. Methods: PAH was induced in 13 male Sprague-Dawley rats. The MCT group (N=4) was injected with a single dose of 60mg/kg of monoctroaline and kept in normoxia for 4 weeks. The SuHx group (N=9) was injected with a single dose of 20mg/kg of sugen, a VEGF inhibitor, and was placed on a hypoxia chamber for 3 weeks followed by 3 weeks of normoxia. 7 animals were used as a control group. In-vivo measurements of RV pressure and volume with preload changes were acquired. To relate ventricular pressure-volume relations to sarcomere mechanics, a computational model of the RV was developed. Using ventricular morphology and volume measurements from PAH groups, sarcomere material mechanics were adjusted to evaluate ES and ED functions in the treated animals. Results: ED pressures rose significantly in the treated groups (31.7 vs. 70.5 and 71.1 mmHg). ED and ES volumes remained the same in SuHx and CTL group, but increased significantly in the MCT group. RV hypertrophy increased in both PAH animal models, but it was significantly higher in the SuHx group. Even though differences in pressure, volume and morphology exist between the PAH groups, SV and CO were preserved in all treated animals. Model material parameters of increased in PAH, significantly in MCT maximal isometric tension. Conclusions: The model analysis suggests compensation to ESP rises was only possible due to a significant increase in the contractility of RV myocardium in the MCT and SuHx animals. No changes in diastolic function were found in the MCT animals, but there was an increase stiffness in the SuHx animals.