Sridhar S, Clayton Richard H
School of Computer Science and Insigneo Institute for in-silico Medicine, University of Sheffield, Sheffield, UK.
Sci Rep. 2025 May 8;15(1):16016. doi: 10.1038/s41598-025-99674-6.
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.
尽管健康心脏中的心肌细胞通常通过缝隙连接与相邻细胞相连，但在纤维化、瘢痕组织或消融线等情况下，心肌细胞可能会与相邻细胞解耦。然而，实验观察到，电传导仍可通过成纤维细胞在这些解耦区域发生。在本文中，我们提出了一种二维组织中心肌细胞与成纤维细胞之间非局部耦合的新模型，并假设这种长程耦合会引发促心律失常的折返波动态。我们通过将成纤维细胞与心肌的近端和远端区域同时耦合来模拟瘢痕及其周围的边界区。我们发现，在这种设置下，边界区本身是瘢痕内外细胞之间耦合的动态结果。我们已经确定了边界区对快速起搏产生的波稳定性的影响。此外，我们已经确定了决定这种几何结构中波动态的关键参数，并描述了复杂波动态背后的机制。这些发现对于我们理解与心肌瘢痕区域相关的心律失常具有重要意义。
