期刊
HEART RHYTHM
卷 12, 期 10, 页码 2115-2124出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.hrthm.2015.06.019
关键词
Delayed afterdepolarization; Conduction block; Reentry; Arrhythmia; Computer simulation
资金
- National Institutes of Health, National Heart, Lung, and Blood Institute [P01 HL078931, R01 HL110791]
- UCLA MSTP Grant [T32 GM008042]
- Swiss Foundation for Grants in Biology and Medicine grant [PASMP3-1273 12]
- Laubisch and Kawata endowments
BACKGROUND Delayed afterdepolarizations (DADs) have been well characterized as arrhythmia triggers, but their role in generating a tissue substrate vulnerable to reentry is not well understood. OBJECTIVE The purpose of this study was to test the hypothesis that random DADs can self-organize to generate both an arrhythmia trigger and a vulnerable substrate simultaneously in cardiac tissue as a result of gap junction coupling. METHODS Computer simulations in 1-dimensional cable and 2-dimensional tissue models were performed. The cellular DAD amplitude was varied by changing the strength of sarcoplasmic reticulum calcium release. Random DAD latency and amplitude in different cells were simulated using gaussian distributions. RESULTS Depending on the strength of spontaneous sarcoplasmic reticulum calcium release and other conditions, random DADs in cardiac tissue resulted in the following behaviors: (1) triggered activity (TA); (2) a vulnerable tissue substrate causing unidirectional conduction block and reentry by inactivating sodium channels; (3) both triggers and a vulnerable substrate simultaneously by generating TA in regions next to regions with subthreshold DADs susceptible to unidirectional conduction block and reentry. The probability of the latter 2 behaviors was enhanced by reduced sodium channel availability, reduced gap junction coupling, increased tissue heterogeneity, and less synchronous DAD latency. CONCLUSION DADs can self-organize in tissue to generate arrhythmia triggers, a vulnerable tissue substrate, and both simultaneously. Reduced sodium channel availability and gap junction coupling potentiate this mechanism of arrhythmias, which are relevant to a variety of heart disease conditions.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据