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Journal of Zhejiang University SCIENCE B

ISSN 1673-1581(Print), 1862-1783(Online), Monthly

Fibroblast proliferation alters cardiac excitation conduction and contraction: a computational study

Abstract: In this study, the effects of cardiac fibroblast proliferation on cardiac electric excitation conduction and mechanical contraction were investigated using a proposed integrated myocardial-fibroblastic electromechanical model. At the cellular level, models of the human ventricular myocyte and fibroblast were modified to incorporate a model of cardiac mechanical contraction and cooperativity mechanisms. Cellular electromechanical coupling was realized with a calcium buffer. At the tissue level, electrical excitation conduction was coupled to an elastic mechanics model in which the finite difference method (FDM) was used to solve electrical excitation equations, and the finite element method (FEM) was used to solve mechanics equations. The electromechanical properties of the proposed integrated model were investigated in one or two dimensions under normal and ischemic pathological conditions. Fibroblast proliferation slowed wave propagation, induced a conduction block, decreased strains in the fibroblast proliferous tissue, and increased dispersions in depolarization, repolarization, and action potential duration (APD). It also distorted the wave-front, leading to the initiation and maintenance of re-entry, and resulted in a sustained contraction in the proliferous areas. This study demonstrated the important role that fibroblast proliferation plays in modulating cardiac electromechanical behaviour and which should be considered in planning future heart-modeling studies.

Key words: Cardiac model, Electromechanics, Fibroblast proliferation

Chinese Summary  <44> 成纤维细胞增殖改变心脏兴奋传导和收缩的仿真研究

研究目的:通过建立心肌-成纤维细胞电力耦合模型,探讨成纤维细胞增殖对心脏兴奋传导和力学收缩的影响。
创新要点:基于人心室肌细胞的实验数据,修正了ten Tusscher等人发表的心室肌模型,构建心肌细胞-成纤维细胞的耦合模型,仿真了成纤维细胞对心肌组织电生理及力学的影响。通过改变耦合模型中重要参数的数值,如网格分辨率、成纤维细胞模型参数、缝隙连接电导等,观察其对心脏去极化、复极化和动作电位周期的影响。
重要结论:在细胞水平上,耦合成纤维细胞使心室肌细胞的动作电位周期延长,主动张力峰值下降(见图4、5)。在组织水平上,成纤维细胞增殖降低兴奋波传导速度并引发传导阻滞(见图6),降低成纤维增殖区域的应变,延长组织的去极化和复极化(见图8),并维持折返(见图10)。

关键词组:心脏模型;电力耦合;成纤维细胞增殖


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DOI:

10.1631/jzus.B1300156

CLC number:

Q66; R540.4

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On-line Access:

2014-03-04

Received:

2013-06-10

Revision Accepted:

2013-09-17

Crosschecked:

2014-02-21

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