Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel.
IEEE Trans Biomed Eng. 2012 May;59(5):1398-407. doi: 10.1109/TBME.2012.2188291. Epub 2012 Feb 16.
Fibroblasts make for the most common nonmyocyte cells in the human heart and are known to play a role in structural remodeling caused by aging and various pathological states, which can eventually lead to cardiac arrhythmias and fibrillation. Gap junction formed between fibroblasts and myocytes have been recently described and were shown to alter the cardiac electrical parameters, such as action potential duration and conduction velocity, in various manners. In this study, we employed computational modeling to examine the effects of fibroblast-myocyte coupling and ratio on automaticity and electrical wave conduction during reentrant activity, with specific emphasis on dynamic phenomena and stability. Our results show that fibroblast density and coupling impact wave frequency in a biphasic way, first increasing wave frequency and then decreasing it. This can be explained by the dual role of the fibroblast cell as a current sink or a current source, depending on the coupled myocytes intracellular potential. We have also demonstrated that wave stability as manifested by the spiral-wave tip velocity and reentrant activity lifespan depends on fibroblast-myocyte coupling and ratio in a complex way. Finally, our study describes the required conditions in which spontaneous activity can occur, as a result of the fibroblasts depolarizing the myocytes' resting potential sufficiently to induce rhythmic pulses without any stimulation applied.
成纤维细胞是人类心脏中最常见的非心肌细胞类型，已知其在衰老和各种病理状态引起的结构重塑中发挥作用，最终可导致心律失常和纤维性颤动。最近描述了成纤维细胞和心肌细胞之间形成的缝隙连接，并表明它们以各种方式改变心脏电参数，例如动作电位持续时间和传导速度。在这项研究中，我们采用计算建模来检查成纤维细胞-心肌细胞偶联和比率对折返活动期间自动性和电波传导的影响，特别强调动态现象和稳定性。我们的结果表明，成纤维细胞密度和成纤维细胞-心肌细胞偶联以双相方式影响波的频率，首先增加波的频率，然后降低波的频率。这可以通过成纤维细胞细胞根据偶联的心肌细胞细胞内电位作为电流汇或电流源的双重作用来解释。我们还表明，波的稳定性（表现为螺旋波尖端速度和折返活动寿命）取决于成纤维细胞-心肌细胞偶联和比率的复杂方式。最后，我们的研究描述了自发活动发生的所需条件，这是由于成纤维细胞去极化心肌细胞的静息电位，足以在没有任何刺激的情况下诱导节律性脉冲。
