Abstract 13391: Increased LV Afterload Improves Rv Function in a Longitudinal Study of RV-Pressure Overloaded Mice

Abstract

Introduction: The left ventricle (LV) is known to transfer kinetic mechanical energy to the right ventricle (RV) during systole. Normally, the RV relies on this mechanical assistance for up to 70% of its pressure generation. However, this biventricular relationship and its effect on RV function has not been explored in the progression in the pressure overloaded RV. In this study, we developed a longitudinal mouse model of pulmonary arterial (PA)-banding concomitant with transverse aortic constriction (TAC) to initiate an adaptive LV remodeling response. We hypothesized that adaptive LV remodeling would improve RV systolic function in an RV pressure overloaded setting. Methods: Surgical PAB was performed on mice to induce RV pressure overload and myocardial remodeling. Mild surgical TAC was performed on these mice 2-weeks (w) post-PAB. Steady-state free precession (SSFP) cardiac magnetic resonance (CMR) imaging (SSFP-CMR) was performed at 1w post-PAB, 1 w post-TAC (PAB-TAC) and 4 w and 7 w post-surgery (n=7). As controls we used Sham (n=5), TAC-only (n=4, TAC) as well as PAB-only (n=4, PAB) mice at 1, 4, and 7 w after surgery. These images were analyzed using feature-tracking (FT) software to compute measurements of ventricular volumes. Results: RV ejection fraction (RVEF) was reduced in PAB mice compared to Sham at 1w (p=0.02, 0.38±0.06 versus 0.52±0.08, respectively). After TAC, PAB-TAC mice showed an increase in RVEF compared to PAB-only mice at 4 w (p=0.03, 0.49±0.04 versus 0.39±0.08, respectively), and at 7 w (p=0.001, 0.50±0.06 versus 0.37±0.1, respectively). Similarly, tricuspid annular plane systolic excursion (TAPSE) showed a decrease in PAB mice compared to sham (p=0.002, 0.85±0.15mm versus 1.73±0.33mm, respectively) and an increase after TAC at 2 w (p=0.001, 1.55±0.29mm versus 0.85±0.15mm, respectively), 4 w (p=0.002, 1.75±0.32mm versus 0.93±0.21mm, respectively), and at 7 w post-surgery (p=0.001, 1.70±0.33mm versus 0.91±0.14mm, respectively). Conclusions: Even though LV-to-RV mechanical energy transfer is well established in normotensive animals, our data supports a mechanistic link between RV systolic function and LV pressure in remodeled and pressure-overloaded RVs.