Role of sodium and calcium dysregulation in tachyarrhythmias in sudden cardiac death.
Role of sodium and calcium dysregulation in tachyarrhythmias in sudden cardiac death.
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DOI：
10.1161/circresaha.116.304678
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发表时间：
2015-06-05
影响因子：
20.1
通讯作者：
Bers DM
中科院分区：
文献类型：
--
作者：
Wagner S;Maier LS;Bers DM
尽管潜在心脏病的治疗有所改善，心源性猝死（SCD）是世界范围内死亡的主要原因。失调的钠钙处理被认为是危及生命的心动过速的主要诱发因素。在心肌细胞中，许多离子通道和转运体，包括电压门控Na和Ca通道，心脏ryanodine受体，Na/Ca交换器和SR Ca- atp酶参与了这种调节。我们已经从单基因疾病中了解了许多与受干扰离子通道功能的病理生理相关性。即使在结构正常的心脏中，单个离子通道门控和/或离子泵活性的变化足以显著增加心律失常的倾向。然而，心衰（HF）患者在许多离子通道和转运体中获得性功能障碍表现出Na和Ca处理以及Ca/钙调蛋白依赖性蛋白激酶的严重失调，并且特别容易发生心律失常。如果我们要改善他们的结果，就必须更深入地了解潜在的心律失常原理。本文综述了心律失常的基本机制、潜在的离子机制及其对离子稳态的影响，以及在心衰等复杂疾病中的情况。
Despite improvements in the therapy of underlying heart disease sudden cardiac death (SCD) is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes many ion channels and transporters, including voltage-gated Na and Ca channels, cardiac ryanodine receptors, Na/Ca-exchanger and SR Ca-ATPase are involved in this regulation. We have learned a lot about the pathophysiological relevance of disturbed ion channel function from monogenetic disorders. Changes in the gating of a single ion channel and/or the activity of an ion pump suffice to dramatically increase the propensity for arrhythmias even in structurally normal hearts. Nevertheless, patients with heart failure (HF) with acquired dysfunction in many ion channels and transporters exhibit profound dysregulation of Na and Ca handling and Ca/calmodulin dependent protein kinase, and are especially prone to arrhythmias. A deeper understanding of the underlying arrhythmic principles is mandatory if we are to improve their outcome. This review addresses basic tachy-arrhythmic mechanisms, the underlying ionic mechanisms and the consequences for ion homeostasis, and the situation in complex diseases like HF.