Re-entrant cardiac arrhythmias in computational models of long QT myocardium

The long QT syndrome (LQTS) is an inherited disorder in which repolarizatio n of cardiac ventricular cells is prolonged. Patients with the LQTS are at an increased risk of ventricular cardiac arrhythmias. Two phenotypes of the inherited LQTS are caused by defects in K+ channels (LQT1 and LQT2) and on e by defects in Na+ channels (LQT3). Patients with LQT1 are more likely to have self-terminating arrhythmias than those with LQT3. The aim of this com putational study was to propose an explanation for this finding by comparin g the vulnerability of normal and LQT tissue to re-entry, and estimating th e likelihood of self-termination by motion of re-entrant waves to an inexci table boundary in simulated LQT1, LQT2 and LQT3 tissue. We modified a model of mammalian cardiac cells to simulate LQT1 by reducing maximal I-Ks condu ctance, LQT2 by reducing maximal I conductance, and LQT3 by preventing comp lete inactivation of I-Na channels. Each simulated phenotype was incorporat ed into a computational model of action potential propagation in one- and t wo-dimensional homogenous tissue. Simulated LQT tissue was no more vulnerab le to re-entry than simulated normal tissue, but the motion of re-entrant w aves in simulated LQT1 tissue was between 2 and 5 times greater than the mo tion of re-entrant waves in simulated LQT2 and LQT3 tissue. These findings suggest that LQT arrhythmias do not result from increased vulnerability to re-entry, and that re-entry once initiated is more likely To self-terminate by moving to an inexcitable tissue boundary in LQT1 than in LQT2 and LQT3. This finding is consistent with clinical observations. (C) 2001 Academic P ress.