Vulnerability to re-entry arising from LPC-induced alterations of cardiac sodium current kinetics: A simulation study

Myocardial ischemia (MI) is the leading cause of morbidity and mortality in the industrialized world. The Gautier et al reported that late sodium current (I_NaL) kinetics was remodelled by Lysophosphatidylcholine (LPC) and provided some new insights into the underlying mechanisms of MI. In this simulation study, the kinetics of LPC-induced sodium channels was incorporated into human ventricular cell models and into 1D and 2D transmural tissue model. The simulations found that the increased heterogeneity of repolarisation by LPC significantly prolonged QT interval and might be anticipated to be proarrhythmic. Meanwhile, LPC would be anticipated to decrease refractoriness of cells, increase temporal width of vulnerable window (VW) and reduce the wavelength necessary for re-entrant circuits causing an increase susceptibility to arrhythmogenesis. Hence, the I_NaL regulated by LPC can be a potential therapeutic target in patients with ischemic heart disease.