Synchronization of chaotic early afterdepolarizations in the genesis of cardiac arrhythmias

被引:198
作者
Sato, Daisuke [1 ]
Xie, Lai-Hua [1 ]
Sovari, Ali A. [1 ]
Tran, Diana X. [4 ]
Morita, Norishige [1 ]
Xie, Fagen [5 ]
Karagueuzian, Hrayr [1 ]
Garfinkel, Alan [1 ,3 ]
Weiss, James N. [1 ,2 ]
Qu, Zhilin [1 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med Cardiol, Cardiovasc Res Lab, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol Sci, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol Cellular & Integrat Physiol Program, Los Angeles, CA 90095 USA
[5] Kaiser Permanente, Res Dept, Pasadena, CA 91101 USA
基金
美国国家卫生研究院;
关键词
chaos; foci; reentry; fibrillation; TORSADE-DE-POINTES; VENTRICULAR-FIBRILLATION; TRIGGERED ACTIVITY; HYDROGEN-PEROXIDE; MECHANISM; DYNAMICS; INITIATION; CHANNELS; TISSUE; PERIOD;
D O I
10.1073/pnas.0809148106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The synchronization of coupled oscillators plays an important role in many biological systems, including the heart. In heart diseases, cardiac myocytes can exhibit abnormal electrical oscillations, such as early afterdepolarizations (EADs), which are associated with lethal arrhythmias. A key unanswered question is how cellular EADs partially synchronize in tissue, as is required for them to propagate. Here, we present evidence, from computational simulations and experiments in isolated myocytes, that irregular EAD behavior is dynamical chaos. We then show in electrically homogeneous tissue models that chaotic EADs synchronize globally when the tissue is smaller than a critical size. However, when the tissue exceeds the critical size, electrotonic coupling can no longer globally synchronize EADs, resulting in regions of partial synchronization that shift in time and space. These regional partially synchronized EADs then form premature ventricular complexes that propagate into recovered tissue without EADs. This process creates multiple hat propagate "shifting'' foci resembling polymorphic ventricular tachycardia. Shifting foci encountering shifting repolarization gradients can also develop localized wave breaks leading to reentry and fibrillation. As predicted by the theory, rabbit hearts exposed to oxidative stress (H2O2) exhibited multiple shifting foci causing polymorphic tachycardia and fibrillation. This mechanism explains how collective cellular behavior integrates at the tissue scale to generate lethal cardiac arrhythmias over a wide range of heart rates.
引用
收藏
页码:2983 / 2988
页数:6
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