Huang Chunli, Song Zhen, Landaw Julian, Qu Zhilin
Department of Medicine, University of California, Los Angeles, Los Angeles, California; Department of Systems Science, Beijing Normal University, Beijing, China.
Department of Medicine, University of California, Los Angeles, Los Angeles, California.
Biophys J. 2020 May 19;118(10):2574-2587. doi: 10.1016/j.bpj.2020.02.008. Epub 2020 Feb 15.
Spatially discordant alternans (SDA) of action potential duration (APD) has been widely observed in cardiac tissue and is linked to cardiac arrhythmogenesis. Theoretical studies have shown that conduction velocity restitution (CVR) is required for the formation of SDA. However, this theory is not completely supported by experiments, indicating that other mechanisms may exist. In this study, we carried out computer simulations using mathematical models of action potentials to investigate the mechanisms of SDA in cardiac tissue. We show that when CVR is present and engaged, such as fast pacing from one side of the tissue, the spatial pattern of APD in the tissue undergoes either spatially concordant alternans or SDA, independent of initial conditions or tissue heterogeneities. When CVR is not engaged, such as simultaneous pacing of the whole tissue or under normal/slow heart rates, the spatial pattern of APD in the tissue can have multiple solutions, including spatially concordant alternans and different SDA patterns, depending on heterogeneous initial conditions or pre-existing repolarization heterogeneities. In homogeneous tissue, curved nodal lines are not stable, which either evolve into straight lines or disappear. However, in heterogeneous itssue, curved nodal lines can be stable, depending on their initial locations and shapes relative to the structure of the heterogeneity. Therefore, CVR-induced SDA and non-CVR-induced SDA exhibit different dynamical properties, which may be responsible for the different SDA properties observed in experimental studies and arrhythmogenesis in different clinical settings.
动作电位时程（APD）的空间不协调交替现象（SDA）已在心脏组织中被广泛观察到，并且与心律失常的发生有关。理论研究表明，传导速度恢复（CVR）是SDA形成所必需的。然而，这一理论并未得到实验的完全支持，这表明可能存在其他机制。在本研究中，我们使用动作电位的数学模型进行了计算机模拟，以研究心脏组织中SDA的机制。我们表明，当存在并起作用的CVR时，例如从组织的一侧进行快速起搏，组织中APD的空间模式会经历空间协调交替或SDA，这与初始条件或组织异质性无关。当CVR不起作用时，例如对整个组织进行同步起搏或在正常/缓慢心率下，组织中APD的空间模式可以有多种解，包括空间协调交替和不同的SDA模式，这取决于异质初始条件或预先存在的复极化异质性。在均匀组织中，弯曲的节点线不稳定，它们要么演变成直线，要么消失。然而，在异质组织中，弯曲的节点线可以是稳定的，这取决于它们相对于异质性结构的初始位置和形状。因此，CVR诱导的SDA和非CVR诱导的SDA表现出不同的动力学特性，这可能是实验研究中观察到的不同SDA特性以及不同临床环境中心律失常发生的原因。
