Combined effects of acquired LQT syndrome by dofetilide and reduced repolarization reserve on human ventricular action potential: A simulation study

The aim of this study was to investigate interactions between acquired long QT syndrome by dofetilide and reduced repolarization reserve in simulated human ventricular cells using prolongation of APD and triangulation of action potential. A Markovian model of hERG capable of reproducing a wild type as well an acquired long QT syndrome by dofetilide was developed and was included into a ventricular cell model for action potential simulation. Dofetilide concentrations used were 7.5, 30 and 100 nM. The endocardial and mid-myocardial cells were paced with different basic cycle lengths (750, 1000 and 1250 ms). The reduced repolarization reserve was reproduced decreasing the IKs current by 50 and 25%. The results pointed out that triangulation offers an additional more sensitive and accurate indicator of the proarrhythmic potential of a drug than APD prolongation alone.