Comparison of the effects on drug concentrations, electrophysiologic parameters, and termination of atrial fibrillation in dogs when procainamide andibutilide are delivered into the right atrium versus intravenously

Introduction: We tested the hypothesis that right intra-atrial (IA) adminis tration of antiarrhythmic drugs resulted in higher peak serum drug concentr ations, greater electrophysiologic effects, and greater efficacy for termin ation of atrial fibrillation (AF) than intravenous (IV) drug delivery. Methods and Results: Eight dogs were treated with 9.7 mg/kg procainamide in fusion and eight dogs with 0.02 mg/kg ibutilide infusion, injected over 5 m inutes. Each dog had both an electrophysiologic (EP) and an AF termination study during IA and IV drug administration at greater than or equal to2-day intervals (total four studies each). Right atrial pacing capture threshold , right atrial effective refractory period (ERP), right atrial and right ve ntricular monophasic action potential (MAP) durations at 70% and 90% of rep olarization (MAPD(70), MAPD(90)), AH, HV, and QT intervals, QRS width, intr a-arterial systolic and diastolic blood pressures, and cardiac output were measured at different time-points. Blood samples were drawn from the corona ry sinus and femoral vein for drug level determination. The right atrium wa s paced at 400-msec cycle length throughout the study. AF was induced by ra pid right atrial pacing and maintained by methacholine infusion at 1.5 to 3 mug/kg/min. The sustained AF was allowed to persist for 10 minutes before starting the antiarrhythmic drug infusion. We found no significant differen ce between the procainamide concentrations in the coronary sinus and femora l vein during IA and IV drug delivery. The time course and extent of increa se in right atrial ERP, MAPD(70), MAPD(90), and all the other measured EP p arameters did not differ between the two routes of drug administration, No significant difference was found in termination of AF between IV (5/7 proca inamide; 4/8 ibutilide) or IA (3/8 procainamide; 3/8 ibutilide) drug delive ry or between drugs (8/15 procainamide; 7/16 ibutilide). Conclusion: Our data do not support any beneficial effect of IA versus IV p rocainamide or ibutilide delivery.