The effect of non-local coupling of fibroblasts on pacing dynamics in a 2D tissue: a simulation study

成纤维细胞非局部耦合对二维组织起搏动力学的影响:一项模拟研究

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Abstract

Although myocytes in healthy hearts are usually coupled to nearest neighbours via gap junctions, under conditions such as fibrosis, in scar tissue, or across ablation lines, myocytes can uncouple from their neighbours. However it has been experimentally observed that electrical conduction can still occur across these uncoupled regions via fibroblasts. In this paper we propose a novel model of non-local coupling between myocytes and fibroblasts in a 2D tissue, and hypothesise that such long-range coupling can give rise to pro-arrhythmic re-entrant wave dynamics. We have simulated the scar and the surrounding border zone via simultaneous coupling of fibroblasts with both proximal and distal regions of myocardium. We find that in this setup the border zone itself is a dynamical outcome of the coupling between cells within and outside the scar. We have determined the effect of the border zone on the stability of waves generated by rapid pacing. Furthermore we have identified key parameters that determine wave dynamics in this geometry, and have also described the mechanism underlying the complex wave dynamics. These findings are of significance for our understanding of cardiac arrhythmias associated with regions of myocardial scar.

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