Prolongation of the QT interval by dofetilide modulates rate-dependent effects of mexiletine on intraventricular conduction

Evaluation of drug induced frequency dependent QT-prolongation using a flexible computer-based programmable stimulator

“…Furthermore, excessive prolongation of the QT-interval is more likely to occur during prolonged periods of bradycardia than at short-lasting decreases in heart rate or single extra beats at longer cycle lengths. This is illustrated in figure 1 showing the relationship between cycle length and QTinterval before and after administration of dofetilide, a class 111 antiarrhythmic drug [6]. QT-interval is not only prolonged at lower heart rates, but this effect is also more pronounced after longer bradycardias (i.e.…”

“…Relationship between cycle length and QTinterval before (open symbols) and after administration of dofetilide (solid symbols). QT-interval has been measured after the first bradycardic stimulus (=restitution) and at steady state (H Todt et al, 1994). do-ss=dofetilide, steady state; do-re=dofetilide, restitution; ba-ss=baseline, steady state; ba-re=baseline, restitution However, with conventional programmable stimulators as used for electrophysiological studies in clinical settings only a limited number of bradycardic stimuli (usually up to 11 beats) in a single train can be applied.…”

“…Adaptation of QT-interval to a sudden change in cycle length from 250ms (beat 0) to 500ms.This programmable stimulator was tested in an openchest anaesthesized guinea pig model[6] to evaluate the rate-dependent effect of droperidol on the QT-interval.…”