So Little Source, So Much Sink: Requirements for Afterdepolarizations to Propagate in Tissue
So Little Source, So Much Sink: Requirements for Afterdepolarizations to Propagate in Tissue
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DOI：
10.1016/j.bpj.2010.06.042
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发表时间：
2010-09-08
影响因子：
3.4
通讯作者：
Weiss, James N.
中科院分区：
文献类型：
--
作者：
Xie, Yuanfang;Sato, Daisuke;Weiss, James N.
早期（埃兹）和延迟后除极（DAD）如何克服组织中的电紧张性源-汇失配而触发室性早搏仍不完全清楚。为了研究这个问题，我们使用兔心室动作电位模型来模拟组织，其中对埃兹或DAD敏感的连续肌细胞的中心区域被不敏感的组织包围。在具有正常纵向传导速度（0.55 m/s）的1D组织中，EAD和仅阈上DAD触发传播动作电位所需的连续易感肌细胞数量分别为70和80。在2D组织中，这些数字增加到6940和7854，在3D组织中增加到696,910和817280。这些数字显着减少缝隙连接电导，模拟纤维化，减少复极储备和心力衰竭电重构。总之，在耦合良好的心脏组织中的源-汇不匹配有力地保护心脏免受由于偶发性后去极化引起的心律失常。结构和电生理重塑显着减少这些数字，但仍然需要埃兹和DAD的同步机制，以克服强大的源-汇不匹配的保护作用。
How early (EADs) and delayed afterdepolarizations (DADs) overcome electrotonic source-sink mismatches in tissue to trigger premature ventricular complexes remains incompletely understood. To study this question, we used a rabbit ventricular action potential model to simulate tissues in which a central area of contiguous myocytes susceptible to EADs or DADs was surrounded by unsusceptible tissue. In 1D tissue with normal longitudinal conduction velocity (0.55 m/s), the numbers of contiguous susceptible myocytes required for an EAD and a barely suprathreshold DAD to trigger a propagating action potential were 70 and 80, respectively. In 2D tissue, these numbers increased to 6940 and 7854, and in 3D tissue to 696,910 and 817,280. These numbers were significantly decreased by reduced gap junction conductance, simulated fibrosis, reduced repolarization reserve and heart failure electrical remodeling. In conclusion, the source-sink mismatch in well-coupled cardiac tissue powerfully protects the heart from arrhythmias due to sporadic afterdepolarizations. Structural and electrophysiological remodeling decrease these numbers significantly but still require synchronization mechanisms for EADs and DADs to overcome the robust protective effects of source-sink mismatch.