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心脏电生理学的第二代计算建模:动作电位对离子浓度变化和代谢抑制的反应。

A second-generation computational modeling of cardiac electrophysiology: response of action potential to ionic concentration changes and metabolic inhibition.

作者信息

Alaa Nour Eddine, Lefraich Hamid, El Malki Imane

机构信息

Department of Mathematics, Laboratory of Applied Mathematics and Computer Science (LAMAI), Faculty of Science and Technology, Cadi Ayaad University, Abdelkarim Elkhattabi Avenue, Marrakech, Morocco.

出版信息

Theor Biol Med Model. 2014 Oct 21;11:46. doi: 10.1186/1742-4682-11-46.

Abstract

BACKGROUND

Cardiac arrhythmias are becoming one of the major health care problem in the world, causing numerous serious disease conditions including stroke and sudden cardiac death. Furthermore, cardiac arrhythmias are intimately related to the signaling ability of cardiac cells, and are caused by signaling defects. Consequently, modeling the electrical activity of the heart, and the complex signaling models that subtend dangerous arrhythmias such as tachycardia and fibrillation, necessitates a quantitative model of action potential (AP) propagation. Yet, many electrophysiological models, which accurately reproduce dynamical characteristic of the action potential in cells, have been introduced. However, these models are very complex and are very time consuming computationally. Consequently, a large amount of research is consecrated to design models with less computational complexity.

RESULTS

This paper is presenting a new model for analyzing the propagation of ionic concentrations and electrical potential in space and time. In this model, the transport of ions is governed by Nernst-Planck flux equation (NP), and the electrical interaction of the species is described by a new cable equation. These set of equations form a system of coupled partial nonlinear differential equations that is solved numerically. In the first we describe the mathematical model. To realize the numerical simulation of our model, we proceed by a finite element discretization and then we choose an appropriate resolution algorithm.

CONCLUSIONS

We give numerical simulations obtained for different input scenarios in the case of suicide substrate reaction which were compared to those obtained in literature. These input scenarios have been chosen so as to provide an intuitive understanding of dynamics of the model. By accessing time and space domains, it is shown that interpreting the electrical potential of cell membrane at steady state is incorrect. This model is general and applies to ions of any charge in space and time domains. The results obtained show a complete agreement with literature findings and also with the physical interpretation of the phenomenon. Furthermore, various numerical experiments are presented to confirm the accuracy, efficiency and stability of the proposed method. In particular, we show that the scheme is second-order accurate in space.

摘要

背景

心律失常正成为全球主要的医疗保健问题之一,会引发包括中风和心源性猝死在内的众多严重疾病。此外,心律失常与心脏细胞的信号传导能力密切相关,是由信号缺陷引起的。因此,对心脏电活动以及支撑诸如心动过速和房颤等危险心律失常的复杂信号模型进行建模,需要一个动作电位(AP)传播的定量模型。然而,已经引入了许多能准确再现细胞中动作电位动态特征的电生理模型。但是,这些模型非常复杂,计算耗时。因此,大量研究致力于设计计算复杂度较低的模型。

结果

本文提出了一个用于分析离子浓度和电势在空间和时间上传播的新模型。在该模型中,离子的传输由能斯特 - 普朗克通量方程(NP)控制,物种的电相互作用由一个新的电缆方程描述。这组方程构成了一个耦合的非线性偏微分方程组,通过数值方法求解。首先我们描述数学模型。为实现对我们模型的数值模拟,我们通过有限元离散化进行,然后选择一种合适的求解算法。

结论

我们给出了在自杀底物反应情况下不同输入场景的数值模拟结果,并与文献中的结果进行了比较。选择这些输入场景是为了直观地理解模型的动态特性。通过访问时间和空间域,结果表明对稳态下细胞膜电势的解释是不正确的。该模型具有通用性,适用于时空域中任何电荷的离子。所获得的结果与文献发现以及该现象的物理解释完全一致。此外,还进行了各种数值实验以证实所提方法的准确性、效率和稳定性。特别是,我们表明该格式在空间上具有二阶精度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fff8/4396161/bc4c3bcadd35/12976_2014_500_Fig1_HTML.jpg

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