Treatment of torsade de pointes with magnesium sulfate

In the theory of electrocardiography the direction of myocardial fibers has been almost ignored. In order to evaluate whether this is proper or not, directional difference of conduction velocity in the ventricular syncytium was examined by capillary microelectrodes. Conduction velocity in the direction of myocardial fibers was found to be usually several times larger than that vertical to them. This difference is significantly large and cannot be ignored even though rapidity of conduction through Purkinje fibers is considered. This statement became more applicable in various abnormal conditions. Thus it is concluded that the direction of myocardial fibers should be given more attention in discussion of propagation of excitation waves in the cardiac ventricle.

Directional Difference of Conduction Velocity in the Cardiac Ventricular Syncytium Studied by Microelectrodes

Simulation study of the ionic mechanisms underlying Torsade de Pointes in a 2D cardiac tissue.

Ischemia in presence of drug induced long QT syndrome 2 (LQTS2) predisposes the tissue to Torsade de pointes (TdP). Reentrant arrhythmias occurring during phase 1B of ischemia have been primarily associated with areas of cellular uncoupling and hyperkalaemia. This study aims to investigate how a region of lowered gap junction conductance (GJC) in presence of LQTS2 can initiate a TdP. Here, a discrete grid of 250x100 cells interconnected using GJCs is taken representing a portion of the transmural wall with anisotropic conduction velocities. LQTS2 is introduced by reducing the potassium current (IKr) of all cells to 50%. An ischemic zone is located almost in the centre of the mid myocardium layer in the form of an elliptic inhomogeneity with varying percentage reduction of GJC compared to the surrounding. Results show that reduction of intercellular conductance in a midmyocardial island can cause a non-sustained reentrant arrhythmia to develop due to premature pacing beats. Addition of hyperkalaemic conditions in the ischemic zone has the effect of prolonging the arrhythmia.

Effect of Regional Cellular Uncoupling in presence of LQTS2 in a 2D Cardiac Tissue

The opportunities and challenges for biophysical modelling of beneficial and adverse drug actions on the heart

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

Study of Polymorphic Ventricular Tachycardia in a 2D Cardiac Transmural Tissue

Arrhythmia generation post ischemia has been linked to loss of cell-to-cell electrical interaction. Arrhythmias like ventricular fibrillation and tachycardia manifest as reentrant circuits at the tissue level. In this paper, a discrete venticular myocyte network of 100×100 cells interconnected using gap junction conductances is simulated along with an ischemic inclusion to study the wave patterns that arise from the ischemic zone due to varied coupling intervals of the stimulus. It is observed from the simulations that premature excitation of the tissue in presence of an ischemic zone can act as a substrate to induce sustained reentrant arrhythmias. Also, these reentrant wave patterns are generated only within a limited window of reduced coupling intervals.

Ponnuraj Kirthi Priya

Papers

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

Simulation study of the ionic mechanisms underlying Torsade de Pointes in a 2D cardiac tissue.

Effect of Regional Cellular Uncoupling in presence of LQTS2 in a 2D Cardiac Tissue

Study of Polymorphic Ventricular Tachycardia in a 2D Cardiac Transmural Tissue

Effect of intercellular conductance and stimuli coupling interval on reentrant arrhythmia