Study of factors affecting the progression and termination of drug induced Torsade de pointes in two dimensional cardiac tissue

Abstract

IntroductionTo study the conditions leading to the initiation and termination of drug induced Torsade de pointes (TdP) along with QT prolongation. MethodsA 2D anisotropic transmural section of the ventricular myocardium is modeled using the TP06 equations and the cells are interconnected with gap junction conductances (GJC). The tissue is remodeled by reducing the repolarization reserve (by increasing calcium current (ICaL)) of all cells thus making them vulnerable to development of early after depolarizations (EADs). ResultsClinical risk conditions like decreased potassium current (IKr), bradycardia, hypokalemia and short-long-short (SLS) triggering sequences are included in the tissue. A pseudo-electrocardiogram is created to realize the intensity of remodeling required in presence of risk factors to initiate TdP. On initiating TdP, the effect of increasing GJC and decreasing ICaL is shown to terminate a non-self-limiting TdP. ConclusionWithout the inclusion of underlying increase in ICaL along with risk factors, TdP cannot be initiated.