ACUTE INTRAVENOUS CONVERSION OF CANINE ATRIAL-FLUTTER - COMPARISON OF ANTIARRHYTHMIC AGENTS

We studied the acute intravenous (i.v.) effects of the antiarrhythmic agents ibutilide, sematilide, lidocaine, and encainide in a canine Y-shaped right atrial incision model of atrial flutter. After baseline determination of atrial effective refractory period (AERP), sustained atrial flutter (AFL) was initiated by atrial pacing in 25 dogs. Each dog then received placebo, followed by sequential doses of a particular agent every 5 min until AFL was terminated or the highest dose was administered. Ibutilide increased AFL cycle length (CL: 26 +/- 6 ms) before termination of AFL in 8 of 8 dogs in 1 min after the effective dose (6 +/- 1 mu g/kg). AERP determined immediately after termination of AFL was significantly increased (44 +/- 7 ms). AFL could not be reinitiated after termination with ibutilide. Sematilide increased AFL CL 12 +/- 6 ms, significantly increased AERP 25 +/- 6 ms, and terminated AFL in 4 of 8 dogs (0.6 +/- 0.2 mg/kg), After sematilide or pacing-induced termination, AFL was reinducible in only 1 dog. Lidocaine terminated AFL in 2 of 5 dogs (2.0 +/- 0.5 mg/kg). AERP was unchanged in both animals, and AFL CL increased by 37 +/- 3 ms, AFL was reinducible in all 5 lidocaine-treated dogs after AFL was terminated. Encainide terminated AFL in 3 of 4 dogs after a dose of 3.0 +/- 0.0 mg/kg. AERP was significantly in creased 77 +/- 10 ms, and AFL CL was markedly increased by 226 +/- 11 ms. AFL could not be reinitiated after termination of AFL by encainide. Ibutilide is more potent and more effective in terminating AFL, as well as in preventing reinitiation of AFL than the other agents at the doses tested in this study. Except with lidocaine, termination of AFL was consistently associated with significant increases in AERP. Prolongation of AFL CL was not consistently associated with termination of AFL.