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人体心房组织离散二维模型中螺旋波的机电动力学

Electro-mechanical dynamics of spiral waves in a discrete 2D model of human atrial tissue.

作者信息

Brocklehurst Paul, Ni Haibo, Zhang Henggui, Ye Jianqiao

机构信息

Engineering Department, Lancaster University, Lancaster, United Kingdom.

Biological Physics Group, School of Physics and Astronomy, University of Manchester, Manchester, United Kingdom.

出版信息

PLoS One. 2017 May 16;12(5):e0176607. doi: 10.1371/journal.pone.0176607. eCollection 2017.

Abstract

We investigate the effect of mechano-electrical feedback and atrial fibrillation induced electrical remodelling (AFER) of cellular ion channel properties on the dynamics of spiral waves in a discrete 2D model of human atrial tissue. The tissue electro-mechanics are modelled using the discrete element method (DEM). Millions of bonded DEM particles form a network of coupled atrial cells representing 2D cardiac tissue, allowing simulations of the dynamic behaviour of electrical excitation waves and mechanical contraction in the tissue. In the tissue model, each cell is modelled by nine particles, accounting for the features of individual cellular geometry; and discrete inter-cellular spatial arrangement of cells is also considered. The electro-mechanical model of a human atrial single-cell was constructed by strongly coupling the electrophysiological model of Colman et al. to the mechanical myofilament model of Rice et al., with parameters modified based on experimental data. A stretch-activated channel was incorporated into the model to simulate the mechano-electrical feedback. In order to investigate the effect of mechano-electrical feedback on the dynamics of spiral waves, simulations of spiral waves were conducted in both the electromechanical model and the electrical-only model in normal and AFER conditions, to allow direct comparison of the results between the models. Dynamics of spiral waves were characterized by tracing their tip trajectories, stability, excitation frequencies and meandering range of tip trajectories. It was shown that the developed DEM method provides a stable and efficient model of human atrial tissue with considerations of the intrinsically discrete and anisotropic properties of the atrial tissue, which are challenges to handle in traditional continuum mechanics models. This study provides mechanistic insights into the complex behaviours of spiral waves and the genesis of atrial fibrillation by showing an important role of the mechano-electrical feedback in facilitating and promoting atrial fibrillation.

摘要

我们在人心房组织的离散二维模型中,研究了机械电反馈和心房颤动诱导的细胞离子通道特性电重构(AFER)对螺旋波动力学的影响。使用离散元法(DEM)对组织的机电特性进行建模。数百万个相互连接的DEM粒子形成一个耦合心房细胞网络,代表二维心脏组织,从而能够模拟组织中电激发波和机械收缩的动态行为。在组织模型中,每个细胞由九个粒子建模,考虑了单个细胞几何形状的特征;同时也考虑了细胞间离散的空间排列。通过将科尔曼等人的电生理模型与赖斯等人的机械肌丝模型强耦合,并根据实验数据修改参数,构建了人心房单细胞的机电模型。在模型中纳入了一个牵张激活通道来模拟机械电反馈。为了研究机械电反馈对螺旋波动力学的影响,在正常和AFER条件下,分别在机电模型和仅电模型中进行了螺旋波模拟,以便直接比较模型之间的结果。通过追踪螺旋波的尖端轨迹、稳定性、激发频率和尖端轨迹的蜿蜒范围来表征螺旋波的动力学。结果表明,所开发的DEM方法考虑了心房组织固有的离散和各向异性特性,提供了一个稳定且高效的人心房组织模型,而这些特性在传统连续介质力学模型中难以处理。本研究通过展示机械电反馈在促进和引发心房颤动中的重要作用,为螺旋波的复杂行为和心房颤动的发生提供了机制性见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a05/5433700/b6ac8f57bb94/pone.0176607.g001.jpg

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