Dofetilide, a new class III antiarrhythmic agent, reduces pacing induced heterogeneity of repolarisation in vivo.
OBJECTIVE
The aim was to determine whether dofetilide, a new class III antiarrhythmic agent, could reduce the heterogeneity of repolarisation produced by rapid cardiac pacing and to compare it with quinidine. Increased heterogeneity of repolarisation times may be causally linked to malignant cardiac re-entrant arrhythmias.


METHODS
Studies were performed in open chest, artificially ventilated, pentobarbitone anaesthetised beagle dogs of 13 to 15 kg body weight. Myocardial electrocardiograms were simultaneously recorded from 31 electrodes located on the left and right ventricular surfaces of the in situ canine heart. Recordings were obtained over a single cardiac cycle during rapid ventricular pacing at the maximum following frequency. Computer assisted measurements of activation time, activation-repolarisation interval, and repolarisation time were performed and the heterogeneity of these measurements calculated. Measurements were performed before treatment and after each incremental intravenous dose of dofetilide (3, 10, 30, and 100 micrograms.kg-1), quinidine (1, 3, and 10 mg.kg-1), or saline vehicle.


RESULTS
Dofetilide increased repolarisation time via a selective prolongation of activation-repolarisation interval, activation time being unchanged. It reduced the heterogeneity of repolarisation time and activation-repolarisation interval, heterogeneity of activation time being unchanged. Quinidine increased repolarisation time by a non-selective increase of both activation-repolarisation interval and activation time. It increased the heterogeneity of activation times which offset a decrease in heterogeneity of activation-repolarisation intervals to produce no change in heterogeneity of repolarisation times.


CONCLUSIONS
Dofetilide, but not quinidine, reduces pacing induced asynchrony of repolarisation in the canine heart and this effect may contribute to its antiarrhythmic activity.
Gwilt
M
M
Pfizer Central Research, Sandwich, Kent, United Kingdom.
King
R C
RC
Milne
A A
AA
Solca
A M
AM
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004562:Electrocardiography; D004594:Electrophysiology; D006339:Heart Rate / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D016276:Ventricular Function
D000889:Anti-Arrhythmia Agents; D010627:Phenethylamines; D013449:Sulfonamides; D011802:Quinidine; C063533:dofetilide