Abstract 13140: Right Ventricular Remodeling and Changes in Tissue Biomechanics in Healthy Aging

Abstract

Introduction: Normal aging in healthy adults has been associated with pulmonary vasculature remodeling and alterations in right ventricular (RV) systolic and diastolic function, which may lead to increased RV afterload and pulmonary hypertension (PH). Previous studies have found a close link between RV biomechanics and function. While current findings suggest a connection between aging and survival rates of PH patients, limited data exist on age-associated differences in the biomechanical properties of RV myocardium. Hypothesis: Aging results in increased RV afterload, hypertrophy, and myocardial stiffening. Methods: Two groups of control (11 weeks) and aging (80 weeks) Sprague-Dawley rats were studied via terminal invasive hemodynamic measurements (n=5/group), quantitative transmural histological analysis (n=3/group; Masson’s trichrome), biaxial mechanical testing (n=6/group) and constitutive modeling (n=6/group) for a comprehensive multi-scale study on the effects of aging on RV biomechanics. Results: Aging increased RV peak pressures by 15% (26.79±0.87 vs. 23.28±0.83 mmHg for aging vs. control; p=0.020). Increased RV wall thickness (0.89±0.06 vs. 0.66±0.04 mm for aging vs. control; p=0.010) and cardiomyocyte width (25.42±0.34 vs. 14.94±0.64 μm for aging vs. control; p<0.001) were observed in the aging group, while not showing any effects on the Fulton index. Histological analyses showed transmural realignment of RV collagen and myofibers towards the apex-to-base direction by 14.6° (p=0.017). This was accompanied by transmural loss of cardiomyocytes (cardiomyocyte area fraction: 88.4%±0.4% vs. 95.3%±0.7% for aging vs. control; p<0.001) and increased myofiber stiffness (169.9±20.6 vs. 65.8±4.7 kPa for aging vs. control; p<0.001). While aging resulted in RV fibrosis (collagen area fraction: 5.1%±0.5% vs. 3.8%±0.1% for aging vs. control; p=0.049), collagen fibers in the aging myocardium showed decreased effective intrinsic stiffness compared to young controls (23.9±3.8 vs. 73.1±15.4 MPa for aging vs. control; p=0.031). Conclusions: Healthy aging has the potential to modulate RV dysfunction via increased myofiber stiffness, fiber reorientation, loss of ventricular cardiomyocytes, RV hypertrophy and fibrosis.