Gender and age based differences in risk of proarrhythmia by dofetilide: A computational model study

The aim of this study was to investigate the risk of proarrhythmia by dofetilide in gender and age based differences using action potential duration and triangulation of action potential. Left ventricular epicardial, midmyocardial and endocardial action potentials were simulated using a modified Luo Rudy model. Sex, age and regional differences in current densities and voltage dependent parameters for I_CaL, IK_r, IK_s, and I_to were incorporated into the model by modifying the equations representing them. A model of dofetilide was developed and included into a ventricular cell model. This study has demonstrated that gender and age based differences in ionic currents and drug induced action of dofetilide might explain in part the higher susceptibility of EADs and prevalence of TdP in adult females and the higher risk of cardiac events in males than females during childhood.