Effects of the antiarrhythmic drug dofetilide on regional heterogeneity of action potential duration: a computer modelling study

DifSerent experimental studies have shown that ventricular cells present several diflerences between epicardium, endocardium and M-cells. M-cells have longer APDs and higher sensitivity to agents with class III actions and they could contribute to APD heterogeneity in the ventriculum. However, in-vivo studies have observed that the strong cellular coupling reduces the APD dispersion in intact heart. We used the Luo and Rudy model (LRdOO) of AP and the model of IKr blockade by the action of dofetilide developed previously by our group ro study the effect of dofetilide (a class III antiarrhythmic drug) on the APD dispersion in a strand of ventricular tissue. Our results show that dofetilide increases dramatically the APD dispersion and may modify the transmural gradient of APR even in normal coupling condirions such as those in intact heart, Higher dispersion and, a more complex behaviour, such as 2:1 block, could appear when the coupling decreases.