Modulation of the regional dispersion of repolarization by the action of class III antiarrhythmic drug dofetilide

It is well known that short-long (S-L) sequences frequently precede the onset of malignant ventricular arrhythmias. Experimental studies have shown that a single long coupled extra-beat (L) after a previous basic cycle length resulted in a critical increase of the dispersion of repolarization pattern that promoted reentrant excitation. However, in normal intact heart little differences in repolarization among different myocardial layers have been observed after abrupt slowing of heart rate. We used the Luo and Rudy model (LRd00) of AP and the model of IKr blockade by the action of dofetilide previously developed by our group to study the effect of dofetilide (a class III antiarrhythmic drug) on the modulation of APD dispersion in a strand of ventricular tissue. Our results show that dofetilide increases dramatically the APD of the strand and that the effect of dofetilide on the modulation of dispersion is complex, indicating that the highest dispersion could appear before the highest effect of the drug is reached