Frequency-dependent electrophysiological effect of ibutilide on human atrium and ventricle

Most of the class III antiarrhythmic agents developed in recent years block s the rapid component of delayed rectifier potassium current (IKr). IKr blo cker shows reverse use-dependency and also may cause torsades de pointes at slower heart rate. Ibutilide fumarate, a novel class III antiarrhythmic ag ent, increases window Na+ current at the action potential plateau phase. We studied the rate-dependent effect of ibutilide on the electrophysiological parameters of human atrium and ventricle. Franz catheter and a pacing cath eter were placed closely in the high right atrium and right ventricular ape x to record monophasic action potentials (MAP) during pacing at cycle lengt h (PCL) of 600 ms and 350 ms in eight patients who underwent electrophysiol ogical study. MAP duration of right atrium (RA-MAPD) and right ventricle (R V-MAPD), effective refractory period of RA and RV (RA-ERP and RV-ERP), intr a-atrial conduction time (IACT) and intra-ventricular conduction time (IVCT ) were measured before and after intravenous administration of ibutilide (0 .01 mg/kg up to 1 mg). A conduction time from RA pacing spike to distal cor onary sinus potential was used to measure IACT, while QRS duration of surfa ce ECG during RV pacing was used to measure IVCT. Ibutilide prolonged RA-MA PD by 60 ms at PCL 600 ]ms and by 53 ms at PCL 350 ms; RV- MAPD by 48 ms at PCL 600 ms and by 55 ms at PCL 350 ms. Ibutilide did not affected RA and R V-ERP/MAPD ratio, IACT, and IVCT. Ibutilide prolongs MAPD and ERP of human atrium and ventricle without reverse use-dependency.