Study of Polymorphic Ventricular Tachycardia in a 2D Cardiac Transmural Tissue
Beta-adrenergic agents are usually contraindicated in patients prone to acquired Torsade de Pointes (TdP). TdP is frequently accompanied by long QT syndrome 2 (LQTS2). Here, we try to simulate TdP in a 2D transmural grid in presence of the above two conditions. Modifications to the TP06 model are made to emulate the differences in action potential (AP) generated from the three types of transmural cells (endocardial, mid- and epicardial cells). The effect of drug-induced LQTS2 is evoked by completely blocking the rapid delayed rectifier potassium current (IKr) in each cell, and beta-adrenergic stimulation is introduced by raising the conductance of l-type calcium current (GCaL) to twice its normal value. This combined effect increases the inducibility of early afterdepolarizations (EADs). The mechanism of EAD generation at cellular level is studied by analysing the ionic currents and calcium dynamics. TdP like polymorphic ventricular arrhythmia is found to develop under slow pacing rates. Spontaneous release of calcium from the sarcoplasmic reticulum triggers an increase in the level of intracellular calcium and inward sodium current through the sodium-calcium exchanger current (INaCa). This prolongs the action potential duration (APD) providing enough time to reactivate ICaL creating an upstroke during the repolarization phase.
KeywordsTorsade de Pointes Long QT syndrome Early afterdepolarization Transmural tissue
This work was funded by the Indian Institute of Technology Madras.
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