Electromechanical and structural alterations in the aging rabbit heart and aorta

Abstract

Aging increases the risk for arrhythmias and sudden cardiac death (SCD). We aimed at elucidating aging-related electrical, functional, and structural changes in the heart and vasculature that account for this heightened arrhythmogenic risk. Young (5-9 mo) and old (3.5-6 yr) female New Zealand White (NZW) rabbits were subjected to in vivo hemodynamic, electrophysiological, and echocardiographic studies as well as ex vivo optical mapping, high-field magnetic resonance imaging (MRI), and histochemical experiments. Aging increased aortic stiffness (baseline pulse wave velocity: young, 3.54 ± 0.36 vs. old, 4.35 ± 0.28 m/s, P < 0.002) and diastolic (end diastolic pressure-volume relations: 3.28 ± 0.5 vs. 4.95 ± 1.5 mmHg/ml, P < 0.05) and systolic (end systolic pressure-volume relations: 20.56 ± 4.2 vs. 33.14 ± 8.4 mmHg/ml, P< 0.01) myocardial elastances in old rabbits. Electrophysiological and optical mapping studies revealed age-related slowing of ventricular and His-Purkinje conduction (His-to-ventricle interval: 23 ± 2.5 vs. 31.9 ± 2.9 ms, P < 0.0001), altered conduction anisotropy, and a greater inducibility of ventricular fibrillation (VF, 3/12 vs. 7/9, P < 0.05) in old rabbits. Histochemical studies confirmed an aging-related increased fibrosis in the ventricles. MRI showed a deterioration of the free-running Purkinje fiber network in ventricular and septal walls in old hearts as well as aging-related alterations of the myofibrillar orientation and myocardial sheet structure that may account for this slowed conduction velocity. Aging leads to parallel stiffening of the aorta and the heart, including an increase in systolic stiffness and contractility and diastolic stiffness. Increasingly, anisotropic conduction velocity due to fibrosis and altered myofibrillar orientation and myocardial sheet structure may contribute to the pathogenesis of VF in old hearts. The aging rabbit model represents a useful tool for elucidating age-related changes that predispose the aging heart to arrhythmias and SCD.

Age-associated abnormalities of intrinsic automaticity of sinoatrial nodal cells are linked to deficient cAMP-PKA-Ca2+signaling

“…Changes between the neonatal period and advanced age have been previously documented in rabbit (2 days vs. 5.6 yr) (1,6) and cat (6 wk vs. 18 yr) SAN function (1,6). Similarly, the present results demonstrate that IBR of the isolated mouse SAN and in cells isolated from the node are reduced in advanced age (Fig.…”

Association of blood pressure and aortic distensibility with P wave indices and PR interval: The Multi-Ethnic Study of Atherosclerosis (MESA)

“…In fact, a parallel stiffening of the aorta and cardiac conduction system has been observed in an aging rabbit model. 31 …”

Arrhythmias in Patients ≥80 Years of Age

“…In addition, pre-clinical studies in rabbits have shown an aging-related slowdown of electrical conduction velocity throughout the His-Purkinje network (8), which is manifested in humans by prolongation of the HV interval. Kuo et al (9) showed that the atrioventricular (AV) nodal recovery curve remains unchanged once one reaches adulthood, whereas the AV nodal effective refractory period becomes slightly longer after age 60 years (9).…”