Role of collagen in right ventricular passive anisotropic viscoelasticity with pulmonary hypertension

Collagen is a structural extracellular protein that contributes to the anisotropic elastic behavior of the right ventricle (RV). It is established that collagen is significantly altered in pulmonary hypertension (PH), including overall content, degree of cross-linking, and fiber alignment. The RV is viscoelastic, though, and how collagen contributes to the overall tissue viscoelastic behavior with PH development remains unknown. Therefore, the aim of this study was to investigate the role of collagen in the anisotropic viscoelasticity of the RV free wall (RVFW) during PH progression. Equibiaxial stress relaxation tests were performed in healthy and PH rat RVFW before and after the enzymatic breakdown of collagen via collagenase. A Fung-type quasilinear viscoelastic constitutive model was then applied to further delineate the changes in RVFW mechanics. We found that collagen degradation significantly reduced RVFW viscosity and elasticity, with stronger effects in the diseased group. The reduction in RVFW elastic behavior was stronger in the longitudinal direction than the circumferential, while the reduction in viscosity was similar between directions in both groups. Constitutive modeling results showed weakened RVFW stiffness after collagenase treatment in both groups, but distinct responses of relaxation strength coefficients between the healthy and diseased groups. In the longitudinal direction, the relaxation strength coefficients were positively correlated with the viscosity to elasticity ratio measured from experimental data in both groups. Our findings demonstrate distinct collagen deposition and morphology between healthy and diseased RVFW, suggesting that RV fibrosis results in unique regulation of RVFW mechanics.