Modulation of Spiral-Wave Dynamics and Spontaneous Activity in a Fibroblast/Myocyte Heterocellular Tissue–-A Computational Study

Abstract

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.