Mechanisms of ventricular arrhythmias elicited by coexistence of multiple electrophysiological remodeling in ischemia: A simulation study.
Mechanisms of ventricular arrhythmias elicited by coexistence of multiple electrophysiological remodeling in ischemia: A simulation study.
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DOI：
10.1371/journal.pcbi.1009388
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发表时间：
2022-04
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
--
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心肌缺血、损伤和梗死是急性冠状动脉综合征（ACS）的三个阶段。在过去的二十年中，大量的研究集中在心肌缺血和MI的单独研究，并表明折返性心律失常的发生往往与心肌缺血或MI有关。然而，缺血性心脏中具有不同程度重构的组织中的致瘤机制尚未完全了解。在这项研究中，生物物理详细的单细胞模型缺血1a，1b，和MI的开发，以模拟在ACS的不同阶段的电生理重构。建立了不同缺血和心肌梗死面积分布的二维组织模型，以研究缺血过程中折返波的启动机制。在二维组织中的模拟结果表明，脆弱的窗口（VW）在同时存在多种缺血性条件下与波传播的动力学与每个单一的病理条件的组织。在多种病理条件下的组织中，折返波主要由两种不同的机制引起：一个是沿着激励波前的沿着不均匀性，特别是穿过缺血1b和MI边界的传导速度（CV）的突然变化，另一个是降低的安全系数（SF）心肌梗死区组织边缘的传导与心肌梗死区的兴奋阈值增加有关。最后，在具有从MI患者的MRI图像重建的瘢痕的3D模型中观察到折返波。这些全面的研究结果提供了新的见解，了解心肌缺血的进展过程中的心脏病风险，并强调了多个病理阶段的重要性，在设计药物治疗缺血性心律失常。电脉冲的异常启动或传导可能导致心律失常，这是发达国家猝死和早死的重要原因。在许多情况下，心律失常伴随着由折返引起的持续性室颤。折返性心律失常的发生常与急性冠脉综合征相关，包括心肌缺血1a、1b和梗死的三个阶段。以往的研究已做了大量的努力，以阐明在心肌缺血或梗死的折返波的启动和维持的机制。然而，在多发性缺血性重构的组织中折返波的启动机制尚未完全清楚。本研究建立了细胞、组织和器官水平的多尺度计算模型。本研究的主要发现是，在多种缺血条件同时存在的折返波主要是由不应期的空间异质性引起的动作电位时程（APD）和CV沿着波前的共同作用，当不同病理条件的边界垂直于激发波的波前。此外，当边界与兴奋波阵面平行时，MI区兴奋阈值的增加以及缺血区兴奋性的降低可诱发折返的产生。这为了解缺血时多种电生理重构共存引起室性心律失常的机制提供了新的思路。
Myocardial ischemia, injury and infarction (MI) are the three stages of acute coronary syndrome (ACS). In the past two decades, a great number of studies focused on myocardial ischemia and MI individually, and showed that the occurrence of reentrant arrhythmias is often associated with myocardial ischemia or MI. However, arrhythmogenic mechanisms in the tissue with various degrees of remodeling in the ischemic heart have not been fully understood. In this study, biophysical detailed single-cell models of ischemia 1a, 1b, and MI were developed to mimic the electrophysiological remodeling at different stages of ACS. 2D tissue models with different distributions of ischemia and MI areas were constructed to investigate the mechanisms of the initiation of reentrant waves during the progression of ischemia. Simulation results in 2D tissues showed that the vulnerable windows (VWs) in simultaneous presence of multiple ischemic conditions were associated with the dynamics of wave propagation in the tissues with each single pathological condition. In the tissue with multiple pathological conditions, reentrant waves were mainly induced by two different mechanisms: one is the heterogeneity along the excitation wavefront, especially the abrupt variation in conduction velocity (CV) across the border of ischemia 1b and MI, and the other is the decreased safe factor (SF) for conduction at the edge of the tissue in MI region which is attributed to the increased excitation threshold of MI region. Finally, the reentrant wave was observed in a 3D model with a scar reconstructed from MRI images of a MI patient. These comprehensive findings provide novel insights for understanding the arrhythmic risk during the progression of myocardial ischemia and highlight the importance of the multiple pathological stages in designing medical therapies for arrhythmias in ischemia. Abnormal initiation or conduction of electrical impulses may lead to cardiac arrhythmias, which are very important cause of sudden and early death in developed countries. In many cases, cardiac arrhythmias are accompanied by ventricular fibrillation sustained by re-entry. The occurrence of reentrant arrhythmias is often associated with acute coronary syndrome, including three phases of myocardial ischemia 1a, 1b, and infarction. Previous studies have made lots of efforts to unravel the mechanisms of the initiation and maintenance of reentry waves during myocardial ischemia or infarction. However, the mechanisms of the initiation of reentrant waves in the tissue with multiple ischemic remodeling are not fully understood. Multi-scale computational models at the cell, tissue, and organ levels were developed in this study. The main finding in this study is that reentrant waves in the simultaneous presence of multiple ischemic conditions were mainly induced by the spatial heterogeneity of refractory periods caused by the co-action of action potential duration (APD) and CV along the wavefront, when the borders of different pathological conditions were perpendicular to the wavefront of the excitation wave. In addition, the increased excitation threshold of MI region as well as the impaired excitability of ischemia region can induce the generation of reentry, when the borders were parallel to the excitation wavefront. This provides insights into mechanisms of ventricular arrhythmias elicited by coexistence of multiple electrophysiological remodeling in ischemia.
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影响因子：
3.7
作者：
Alday EA;Ni H;Zhang C;Colman MA;Gan Z;Zhang H
通讯作者：
Zhang H
影响因子：
37.8
作者：
LUE, WM;BOYDEN, PA
通讯作者：
BOYDEN, PA
DOI：
10.1073/pnas.1718211115
发表时间：
2018-03-27
影响因子：
11.1
作者：
Hegyi, Bence;Bossuyt, Julie;Chen-Izu, Ye
通讯作者：
Chen-Izu, Ye
影响因子：
3.7
作者：
Arevalo H;Plank G;Helm P;Halperin H;Trayanova N
通讯作者：
Trayanova N
影响因子：
2.7
作者：
Overbaugh, Kristen J.
通讯作者：
Overbaugh, Kristen J.