Cardiovascular Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
Am J Physiol Heart Circ Physiol. 2012 Apr 15;302(8):H1625-35. doi: 10.1152/ajpheart.00960.2011. Epub 2012 Feb 3.
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.
衰老会增加心律失常和心源性猝死（SCD）的风险。我们旨在阐明与衰老相关的心脏和血管的电、功能和结构变化，这些变化导致心律失常风险增加。年轻（5-9 个月）和年老（3.5-6 岁）的雌性新西兰白兔（NZW）接受了体内血流动力学、电生理和超声心动图研究以及体外光学标测、高场磁共振成像（MRI）和组织化学实验。衰老增加了主动脉僵硬度（基础脉搏波速度：年轻组为 3.54 ± 0.36 m/s，老年组为 4.35 ± 0.28 m/s，P < 0.002）和舒张期（舒张末期压力-容积关系：3.28 ± 0.5 mmHg/ml vs. 4.95 ± 1.5 mmHg/ml，P < 0.05）和收缩期（收缩末期压力-容积关系：20.56 ± 4.2 mmHg/ml vs. 33.14 ± 8.4 mmHg/ml，P < 0.01）心肌弹性。电生理和光学标测研究显示，心室和希氏-浦肯野传导（希氏至心室的时间间隔：23 ± 2.5 ms vs. 31.9 ± 2.9 ms，P < 0.0001）、传导各向异性改变以及心室颤动（VF）易感性增加（3/12 对 7/9，P < 0.05）在老年兔子中。组织化学研究证实，心室纤维化与衰老有关。MRI 显示，老年心脏的心室和间隔壁的自主浦肯野纤维网络恶化，以及肌原纤维取向和心肌片结构的衰老相关改变，这些可能导致传导速度减慢。衰老导致主动脉和心脏的僵硬程度平行增加，包括收缩期僵硬度和收缩力以及舒张期僵硬度增加。由于纤维化和肌原纤维取向以及心肌片结构的改变导致的各向异性传导速度增加，可能导致老年心脏的 VF 发病机制。衰老兔模型是阐明使衰老心脏易发生心律失常和 SCD 的与年龄相关变化的有用工具。
