Abstract

Healthy aging has been associated with alterations in pulmonary vascular and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work, we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative transmural histological analysis were employed to study two groups of male Sprague-Dawley rats: control (11 weeks) and aging (80 weeks). Aging was associated with increases in RV peak pressures (+17%, p = 0.017), RV contractility (+52%, p = 0.004), and RV wall thickness (+38%, p = 0.001). Longitudinal realignment of RV collagen (16.4°, p = 0.013) and myofibers (14.6°, p = 0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. Aging led to increased RV myofiber stiffness (+141%, p = 0.003), in addition to a bimodal alteration in the biaxial biomechanical properties of the RV free wall, resulting in increased tissue-level stiffness in the low-strain region, while progressing into decreased stiffness at higher strains. Our results demonstrate that healthy aging may modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fibrosis, fiber reorientation, and altered mechanical properties in male Sprague-Dawley rats. Similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload. These findings may help our understanding of age-related changes in the cardiovascular fitness and response to disease.

Highlights

  • Healthy aging is associated with alterations in right ventricular (RV) structure and function in subjects with no underlying cardiopulmonary disease [1,2,3,4,5]

  • Our study provides preliminary insights into how healthy aging may modulate RV remodeling and lays the groundwork for future studies to further evaluate the age-related differences in RV response to pressure overload

  • Aging resulted in increased RV peak pressures

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Summary

Introduction

Healthy aging is associated with alterations in right ventricular (RV) structure and function in subjects with no underlying cardiopulmonary disease [1,2,3,4,5]. Aging has been shown to result in pulmonary artery (PA) remodeling [6, 7] and increased pulmonary vascular resistance [5, 8]. Echocardiographic studies on RV function have found a strong positive correlation between aging and PA systolic pressures [9, 10]. Previous work has demonstrated that healthy aging results in diminished RV hypertrophy in response to pressure overload [11, 15]. Age-related differences exist in the survival rates of pulmonary hypertension (PH) patients in which older patients show more severe characteristics with poor response to therapeutic interventions [16, 17]

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