Antiarrhythmic and electrophysiologic effects of intravenous ibutilide and sotalol in the canine sterile pericarditis model

Introduction: Atrial arrhythmias are a frequent clinical complication following open heart surgery. We compared the Class III agents d,l-sotalol and ibutilide fumarate in an intravenous cross-over study using the canine atrial sterile pericarditis model. Methods and Results: We studied pacing-induced sustained atrial Butter over a 7-day postsurgical period in conscious dogs, alternating analysis of ibutilide (1.0 to 30.0 mu g/kg) and d,l-sotalol (0.1 to 3.0 mg/kg). Ibutilide significantly increased atrial Butter cycle length (AFL CL) 11 +/- 2 msec and atrial effective refractory period (AERP) 13 +/- 2 msec, and terminated atrial Butter in all cases (n = 12) following a mean dose of 6 +/- 2 mu g/kg. Plasma concentrations of ibutilide were 53 +/- 13 ng/mL. Ventricular effective refractory period (VERP) was not significantly affected (4 +/- 2 msec). Following termination with ibutilide, atrial Butter could be reinitiated in 1 of 12 trials, and was nonsustained (40-sec duration). Sotalol significantly increased AFL CL 23 +/- 3 msec and terminated atrial Butter in 8 of 12 trials following a mean dose of 1.5 +/- 0.4 mg/kg, AERP and VERP were significantly increased 20 +/- 6 and 12 +/- 2 msec, respectively, The incidence of reinduced atrial Butter was 9 of 12 trials (P less than or equal to 0.05 vs ibutilide) (7 nonsustained 57 +/- 7 sec duration, and 2 sustained). Sotalol failed to terminate atrial Butter in two dogs on days 1 and 5, despite increases in AFL CL (21 +/- 8 msec) and AERP (16 +/- 9 msec), whereas on day 3, ibutilide (20 +/- 7 mu g/kg) terminated atrial Butter in those two dogs while increasing AFL CL and AERP 18 +/- 6 and 15 +/- 0 msec, respectively. Conclusion: Both sotalol and ibutilide terminate atrial Butter in this model. Ibutilide converted atrial Butter in dogs in which sotalol was not successful. Following atrial Butter termination, ibutilide had a lower incidence of reinduced arrhythmias compared to sotalol. Ibutilide produced atrial antiarrhythmic effects while having no significant electrophysiologic effects on the ventricle.