Effects of transmural electrical heterogeneities and electrotonic interactions on the dispersion of cardiac repolarization and action potential duration: A simulation study
Effects of transmural electrical heterogeneities and electrotonic interactions on the dispersion of cardiac repolarization and action potential duration: A simulation study
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DOI：
10.1016/j.mbs.2006.06.002
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发表时间：
2006-11-01
影响因子：
4.3
通讯作者：
Taccardi, B.
中科院分区：
文献类型：
--
作者：
Colli-Franzone, P.;Pavarino, L. F.;Taccardi, B.
文献表明，从心室壁不同深度分离的肌细胞具有不同的动作电位持续时间（apd）。当这些肌细胞嵌入心室壁时，它们的不均匀性影响了复极化的顺序和apd在整个心室壁的实际分布。在本文中，我们实现了一个数学模型来模拟(a)非均匀固有膜特性（特别是非均匀apd）和(b)当肌细胞嵌入心室心肌时调节apd的电紧张电流的综合效应。特别地，我们研究了(a)和(b)对心室内的激发和复极化序列以及apd分布的影响。我们实现了一个单域组织表示，包括正交异性、跨壁纤维旋转和均匀或非均匀跨壁固有膜性质，根据第一阶段的Luo-Rudy膜离子模型建模。利用平行有限元求解器在空间上采用结构等参数三线性有限元，在时间上采用半隐式自适应方法，对直角平板进行了三维仿真。心外膜或心内膜起搏引起的兴奋和复极序列的模拟表明，在均匀平板上，复极化通路大致遵循激活序列。相反，在本研究中考虑的异质病例中，我们观察到两个复极化波阵面分别从外表面和心内膜面开始，并在壁厚上碰撞，在一个病例中，一个额外的复极化波从壁内部位开始。在经壁心内膜外方向引入非均匀性对复极序列和APD弥散均有影响，但这些影响仅在经壁平面上明显可见。相比之下，在平行于外膜和心内膜的平面上，APD的分布仍然与均匀模型中观察到的非常相似。因此，心外膜表面（或与其平行的任何其他壁内表面）的复极序列和APD弥散模式并未显示均匀的跨壁异质性。(c) 2006爱思唯尔公司版权所有。
It has been shown in the literature that myocytes isolated from the ventricular walls at various intramural depths have different action potential durations (APDs). When these myocytes are embedded in the ventricular wall, their inhomogeneous properties affect the sequence of repolarization and the actual distribution of the APDs in the entire wall. In this article, we implement a mathematical model to simulate the combined effect of (a) the non-homogeneous intrinsic membrane properties (in particular the non-homogeneous APDs) and (b) the electrotonic currents that modulate the APDs when the myocytes are embedded in the ventricular myocardium. In particular, we study the effect of (a) and (b) on the excitation and repolarization sequences and on the distribution of APDs in the ventricles. We implement a Monodomain tissue representation that includes orthotropic anisotropy, transmural fiber rotation and homogeneous or heterogeneous transmural intrinsic membrane properties, modeled according to the phase I Luo-Rudy membrane ionic model. Three-dimensional simulations are performed in a cartesian slab with a parallel finite element solver employing structured isoparametric trilinear finite elements in space and a semi-implicit adaptive method in time.Simulations of excitation and repolarization sequences elicited by epicardial or endocardial pacing show that in a homogeneous slab the repolarization pathways approximately follow the activation sequence. Conversely, in the heterogeneous cases considered in this study, we observed two repolarization wavefronts that started from the epi and the endocardial faces respectively and collided in the thickness of the wall and in one case an additional repolarization wave starting from an intramural site. Introducing the heterogeneities along the transmural epi-endocardial direction affected both the repolarization sequence and the APD dispersion, but these effects were clearly discernible only in transmural planes. By contrast, in planes parallel to epi- and endocardium the APD distribution remained remarkably similar to that observed in the homogeneous model. Therefore, the patterns of the repolarization sequence and APD dispersion on the epicardial surface (or any other intramural surface parallel to it) do not reveal the uniform transmural heterogeneity. (c) 2006 Elsevier Inc. All rights reserved.