Abstract 14407: Right Ventricular Myocardial Stiffening is Associated With Pulmonary Arterial Stiffening in Pulmonary Hypertension

Abstract

Introduction: Pulmonary hypertension (PH) increases vascular resistance in the lung leading to remodeling of the proximal pulmonary artery (PA). PH also leads to the right ventricular (RV) remodeling following increased RV afterload. Studies of tissue remodeling in PH have focused on either the RV or PA, leaving the understanding of the RV-PA remodeling relationship elusive. We hypothesize that PA proximal tissue stiffening is associated with RV free wall (RVFW) stiffening. Methods: The mild model of PH was developed by placing SD rats (n=6) in a hypoxia chamber (10% O2) for 3 weeks, followed by one week of normoxia. The severe model of PH was developed by injecting one dose of SU5416 (20 mg/kg sc) into CDF rats (n=6) followed by the hypoxia protocol. Control rats (n=6 each for SD and CDF) were kept in normoxia at all times. Each group was half male and half female. RVFW and main PA tissues were harvested and characterized through mechanical tests. Tissue stiffness was calculated as the slope of the ensemble stress-strain curve (sum of circumferential and longitudinal stress) at a large strain (>30%) for the RVFW and PA specimens. Results: RVSP increased, and PAT decreased in both models. These changes were significant only in the severe model (Figs. 1A, B). Similarly, RVFW and PA stiffnesses increased significantly only in the severe model (Figs. 1C, D). A significant positive correlation between RVFW and PA stiffness was observed (R2 = 0.59, p=0.0001, Fig. 1E). Conclusions. Our results demonstrate, for the first time, a significant correlation between RVFW and PA stiffening in PH. Proximal PA stiffening changes the pulsatile component of the RV afterload, contributing to the RVFW stiffening, which is known to be a key precursor of RV failure. Our results suggest that the proximal PA stiffening may worsen RV stiffening independent of increases in PA distal resistance. Further studies are needed to determine the role of resistive vs. pulsatile RV afterload in the outcome of RV remodeling.