Contribution of the Mechanical Loads to Susceptibility to Arrhythmia in Subendocardial and Subepicardial Ventricular Myocytes

Abstract

Motivation: It is shown that repolarisation alternans is initiated in the endocardial (ENDO) regions rather than the epicardium (EPI) in the left ventricle (LV) of different animal species (Cordeiro et al, 2007). However, possible contribution of the mechanical factors to the development of rhythm disturbances in ENDO and EPI myocytes has not been sufficiently investigated.Methods: We have shown recently that intracellular mechanisms of mechano-electric feedback contribute to regional differences in the electrical and mechanical activity between virtual ENDO and EPI ventricular cardiomyocytes of guinea pig (Vasilyeva et al, 2012). In this study we used the models to study effects of the mechanical conditions on vulnerability of EPI and ENDO myocytes to rhythm disturbances induced by an increased density of fast sodium current (INa).Results: In isometric (heavy-loaded) mode of contractions, increased INa caused early afterdepolarizations (EAD) in ENDO, but not in EPI cells, along with action potential (AP) and contraction alteration, rapid fall down of the twitch force with subsequent force recovery in several beats.In isotonic mode of contractions, increased INa induced the similar responses in ENDO cells as under isometric conditions independently of the afterload value.In EPI cells low-loaded mode of contractions induced spontaneous excitations, which completely stopped cell shortening (sudden cardiac arrest).Conclusion: The modeling results suggest that ENDO myocytes are more vulnerable to EAD at increased INa density than EPI cells in rather wide range of the mechanical loads. A decrease in the mechanical load may contribute to arrhythmia induction in both the EPI and ENDO cardiomyocytes. Supported by UB of the RAS (12-M-14-2009, 12-П-4-1067) and RBRF (14-01-31134, 13-04-00365).