Role of Sodium and Calcium Dysregulation in Tachyarrhythmias in Sudden Cardiac Death

被引:89
作者
Wagner, Stefan [1 ]
Maier, Lars S. [1 ]
Bers, Donald M. [2 ]
机构
[1] Univ Hosp Regensburg, Dept Internal Med 2, D-93053 Regensburg, Germany
[2] Univ Calif Davis, Dept Pharmacol, Davis, CA 95616 USA
关键词
alternans; arrhythmias; calcium; calmodulin-dependent kinase II; sodium; CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE; SARCOPLASMIC-RETICULUM CA2+; T-WAVE ALTERNANS; POLYMORPHIC VENTRICULAR-TACHYCARDIA; ACTION-POTENTIAL PROLONGATION; BETA-ADRENERGIC STIMULATION; HISTONE H3 PHOSPHORYLATION; ACUTE-CORONARY-SYNDROME; LONG QT SYNDROME; LATE I-NA;
D O I
10.1161/CIRCRESAHA.116.304678
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Despite improvements in the therapy of underlying heart disease, sudden cardiac death 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 the activity of an ion pump suffice to dramatically increase the propensity for arrhythmias even in structurally normal hearts. Nevertheless, patients with heart failure 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 tachyarrhythmic mechanisms, the underlying ionic mechanisms and the consequences for ion homeostasis, and the situation in complex diseases like heart failure.
引用
收藏
页码:1956 / 1970
页数:15
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