Rossi Stefano, Fortunati Ilaria, Carnevali Luca, Baruffi Silvana, Mastorci Francesca, Trombini Mimosa, Sgoifo Andrea, Corradi Domenico, Callegari Sergio, Miragoli Michele, Macchi Emilio
Department of Life Sciences, University of Parma, Parma, Italy; CERT, Center of Excellence for Toxicological Research, INAIL, ex ISPESL, University of Parma, Parma, Italy.
Department of Life Sciences, University of Parma, Parma, Italy.
PLoS One. 2014 Nov 14;9(11):e112697. doi: 10.1371/journal.pone.0112697. eCollection 2014.
Advanced age alone appears to be a risk factor for increased susceptibility to cardiac arrhythmias. We previously observed in the aged rat heart that sinus rhythm ventricular activation is delayed and characterized by abnormal epicardial patterns although conduction velocity is normal. While these findings relate to an advanced stage of aging, it is not yet known when and how ventricular electrical impairment originates and which is the underlying substrate. To address these points, we performed continuous telemetry ECG recordings in freely moving rats over a six-month period to monitor ECG waveform changes, heart rate variability and the incidence of cardiac arrhythmias. At the end of the study, we performed in-vivo multiple lead epicardial recordings and histopathology of cardiac tissue. We found that the duration of ECG waves and intervals gradually increased and heart rate variability gradually decreased with age. Moreover, the incidence of cardiac arrhythmias gradually increased, with atrial arrhythmias exceeding ventricular arrhythmias. Epicardial multiple lead recordings confirmed abnormalities in ventricular activation patterns, likely attributable to distal conducting system dysfunctions. Microscopic analysis of aged heart specimens revealed multifocal connective tissue deposition and perinuclear myocytolysis in the atria. Our results demonstrate that aging gradually modifies the terminal part of the specialized cardiac conducting system, creating a substrate for increased arrhythmogenesis. These findings may open new therapeutic options in the management of cardiac arrhythmias in the elderly population.
仅高龄似乎就是心律失常易感性增加的一个风险因素。我们之前在老年大鼠心脏中观察到,窦性心律时心室激动延迟,其特征为心外膜模式异常,尽管传导速度正常。虽然这些发现与衰老的晚期阶段有关,但目前尚不清楚心室电功能障碍何时以及如何起源,其潜在机制是什么。为了解决这些问题,我们在自由活动的大鼠身上进行了为期六个月的连续遥测心电图记录,以监测心电图波形变化、心率变异性和心律失常的发生率。在研究结束时,我们进行了体内多导联心外膜记录和心脏组织的组织病理学检查。我们发现,随着年龄的增长,心电图波和间期的持续时间逐渐增加,心率变异性逐渐降低。此外,心律失常的发生率逐渐增加,房性心律失常超过室性心律失常。心外膜多导联记录证实了心室激动模式的异常,这可能归因于远端传导系统功能障碍。对老年心脏标本的显微镜分析显示,心房有多灶性结缔组织沉积和核周肌细胞溶解。我们的结果表明,衰老会逐渐改变心脏特殊传导系统的终末部分,为心律失常的增加创造了条件。这些发现可能为老年人心律失常的管理开辟新的治疗选择。