In silico analysis of the contribution of cardiomyocyte-fibroblast electromechanical interaction to the arrhythmia

Abstract

Although fibroblasts are about 5–10 times smaller than cardiomyocytes, their number in the ventricle is about twice that of cardiomyocytes. The high density of fibroblasts in myocardial tissue leads to a noticeable effect of their electromechanical interaction with cardiomyocytes on the electrical and mechanical functions of the latter. Our work focuses on the analysis of the mechanisms of spontaneous electrical and mechanical activity of the fibroblast-coupled cardiomyocyte during its calcium overload, which occurs in a variety of pathologies, including acute ischemia. For this study, we developed a mathematical model of the electromechanical interaction between cardiomyocyte and fibroblasts and used it to simulate the impact of overloading cardiomyocytes. In contrast to modeling only the electrical interaction between cardiomyocyte and fibroblasts, the following new features emerge in simulations with the model that accounts for both electrical and mechanical coupling and mechano-electrical feedback loops in the interacting cells. First, the activity of mechanosensitive ion channels in the coupled fibroblasts depolarizes their resting potential. Second, this additional depolarization increases the resting potential of the coupled myocyte, thus augmenting its susceptibility to triggered activity. The triggered activity associated with the cardiomyocyte calcium overload manifests itself in the model either as early afterdepolarizations or as extrasystoles, i.e., extra action potentials and extra contractions. Analysis of the model simulations showed that mechanics contribute significantly to the proarrhythmic effects in the cardiomyocyte overloaded with calcium and coupled with fibroblasts, and that mechano-electrical feedback loops in both the cardiomyocyte and fibroblasts play a key role in this phenomenon. Copyright © 2023 Kursanov, Balakina-Vikulova, Solovyova, Panfilov and Katsnelson.