Jin Hongwei, Lyon Alexander R, Akar Fadi G
Division of Cardiology, Cardiovascular Research Center, Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York, USA.
Pacing Clin Electrophysiol. 2008 Aug;31(8):1048-56. doi: 10.1111/j.1540-8159.2008.01134.x.
Heart failure (HF) claims over 200,000 lives annually in the United States alone. Approximately 50% of these deaths are sudden and unexpected, and presumably the consequence of lethal ventricular tachyarrhythmias. Electrical remodeling that occurs at the cellular and tissue network levels predisposes patients with HF to malignant arrhythmias. Our limited understanding of fundamental arrhythmia mechanisms has hampered the development of effective treatment strategies for these patients.
In this review, we outline recent advances in our understanding of arrhythmia mechanisms in the failing heart, highlighting various aspects of remodeling of ion channels, calcium handling proteins, and gap junction-related molecules. As will be discussed, these changes promote the prolongation of the action potential, the enhancement of spatio-temporal gradients of repolarization, the formation of calcium-mediated triggers and conduction abnormalities, all of which combine to form an electrophysiological substrate that is ripe for the genesis of lethal arrhythmias and sudden cardiac death.
仅在美国，心力衰竭（HF）每年就导致超过20万人死亡。其中约50%的死亡是突然且意外的，推测是致命性室性心律失常的后果。在细胞和组织网络水平发生的电重构使HF患者易发生恶性心律失常。我们对基本心律失常机制的有限理解阻碍了针对这些患者的有效治疗策略的发展。
在本综述中，我们概述了在理解衰竭心脏心律失常机制方面的最新进展，重点介绍了离子通道、钙处理蛋白和缝隙连接相关分子重构的各个方面。如将讨论的，这些变化促进动作电位延长、复极时空梯度增强、钙介导触发因素的形成和传导异常，所有这些共同形成了一个电生理基质，极易引发致命性心律失常和心源性猝死。
