Right Ventricular Stiffening and Function Are Associated With Main Pulmonary Artery Remodeling in a Rat Model of Pulmonary Hypertension

BACKGROUND: Coupling between right ventricular (RV) function and the pulmonary vasculature determines outcomes in pulmonary arterial (PA) hypertension. The mechanics of the main PA (mPA) is an important but understudied determinant of RV-PA coupling. To investigate the histology and mechanics of PA in relationship to RV remodeling, mechanics, hemodynamics, and coupling in experimental PA hypertension. METHODS: In a sugen-hypoxia rat model of PA hypertension, RV hemodynamics were assessed by conductance catheters. Active tension-strain curves were generated using echocardiography. mPA and RV free wall were harvested to determine their macrostructure and microstructure, composition, and mechanical properties. Comprehensive multivariate analyses elucidated relationships between PA and RV mechanics, structure, and coupling. RESULTS: Pulmonary hypertensive mPAs developed fibrosis relative to healthy controls, as did RVs, which also hypertrophied, with reorientation of muscle fibers toward a trilayer architecture reminiscent of normal left ventricular architecture. Increased glycosaminoglycan deposition and increased collagen-to-elastin ratio in PA, and increased collagen, as well as hypertrophy and reorganization of myofibers in RV, led to increased stiffness. This increase in stiffness was more pronounced in the longitudinal direction in the high- and low-strain regime for PA and RV, respectively, causing increased mechanical anisotropy. mPA stiffening correlated significantly with RV tissue mechanical remodeling and reduced systolic performance, cardiac output, and RV-PA coupling. CONCLUSIONS: Compositional, structural, and mechanical changes in mPA correlate with adverse RV remodeling, mechanics, function, and coupling in PA hypertension. Therefore, increasing mechanical compliance of the large PAs may be an important and novel therapeutic strategy for mitigating RV failure.