The Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties: A Pilot Study

Figures

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  Figure 1. The framework used to study RV remodeling with healthy aging. In vivo terminal invasive hemodynamic measurements were performed on young controls and aging Sprague-Dawley rats, followed by harvesting the heart and morphological measurements, biaxial mechanical testing, constitutive modeling, and quantitative transmural histological analysis. The blue dots in the “Morphological Measurement” panel demonstrate the boundaries of the RV free wall, while the Circ-Long coordinate system indicates the orientation of square specimens harvested for mechanical testing. RV, Right ventricle; OT, Outflow tract; Circ, Circumferential; Long, Longitudinal.

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  Figure 2. Hemodynamic measures of the effects of healthy aging on RV (A) Heart rate, (B) Peak pressure, (C) End-diastolic pressure, (D) dpdtmax (positive side) and dpdtmin (negative side), (E) Contractility index, and (F) The preload-independent measure of relaxation (tau). Healthy aging significantly increased RV peak pressures and the load-dependent measures of RV contractility (dpdtmax and contractility index), while not affecting the heart rate, end-diastolic pressures (EDP), and relaxation function (dpdtmin and tau). Error bars represent standard error of the mean (SEM). *Indicates p < 0.05. RV, Right ventricle; BPM, Beats per minute; EDP, End-diastolic pressure; dpdtmax and min, Load-dependent measures of RV contractility and relaxation; n.s, Non-significant.

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  Figure 3. Effects of healthy aging on (A) Biaxial mechanical properties of RV myocardium, (B) Effective fiber-ensemble (EFE) mechanical properties of combined collagen-myofiber bundles, (C) Effective myofiber stiffness, (D) Collagen recruitment strain, (E) Strain energy maps of the RVFW in the low-strain region (circumferential-longitudinal strain space), and (F) Strain energy maps of the RVFW in the high-strain region. Healthy aging modulates the biomechanical properties of the RVFW in a bimodal manner by resulting in increased circumferential and longitudinal stiffness under lower strains, while progressing to decreased biaxial stiffness at higher strains. Significant myofiber stiffening was observed with healthy aging. Specimens in the aging cohort demonstrate higher levels of strain energy at equivalent levels of deformation compared to controls in the low strain region (indicating RVFW stiffening), while showing lower strain energy in the high-strain region (indicating a more compliant RVFW). Error bars represent standard error of the mean (SEM). *Indicates p < 0.05. RV, Right ventricle; RVFW, Right ventricular free wall; 2nd P-K Stress, 2nd Piola-Kirchhoff stress; Circ,…

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  Figure 4. Histological analysis of the effects of healthy aging on RV structure. (A) Representative transmural histological sections of the RVFW (Red/Pink: Myofiber, Blue: Collagen) and effects of aging on (B) Cardiomyocyte hypertrophy (myocyte width), (C) Transmural myofiber orientations, (D) Transmural collagen fiber orientations, (E) Dominant myofiber orientations, (F) Transmural myofiber content (area fraction), (G) Transmural collagen content (area fraction), and (H) Transmural collagen fiber coherency. Healthy aging results in cardiomyocyte hypertrophy, in addition to reorientation of sub-endocardial collagen and myofibers toward the longitudinal direction. This is accompanied by cardiomyocyte loss, RVFW fibrosis, and decreased collagen fiber coherency. Error bars represent standard error of the mean (SEM). *Indicates p < 0.05. RV, Right ventricle; RVFW, Right ventricular free wall; Epi, Epicardium; Mid, Mid-ventricular region; Endo, Endocardium.