We investigated whether rapid administration of a low dose of flecainide, either intratracheally or intravenously (IV), could accelerate conversion of atrial fibrillation (AF) while reducing adverse ventricular effects. Methods: Flecainide was delivered via intratracheal administration at 1.5mg/kg bolus and compared to IV infusion at 1.0mg/kg over 2min (lower-dose, rapid) and 2.0mg/kg over 10 min (ESC guideline) in closed-chest, anesthetized Yorkshire pigs. Catheters were fluoroscopically positioned in right atrium to measure atrial depolarization (Pa) duration and left ventricle (LV) to measure QRS complex duration and contractility (LV dP/dt) during atrial pacing at 140 beats/min. Flecainide was delivered intratracheally via a catheter positioned at the bifurcation of the main bronchi. AF was induced by intrapericardial administration of acetylcholine followed by burst pacing.
Oral and IV routes for delivery of flecainide (FLEC) for acute cardioversion of atrial fibrillation (AF) have drawbacks: high doses (150-300 mg) and 2- to 4- hours wait time for cardioversion with oral dosing and hospitalization for IV administration. Studies in large animal models of AF suggest that FLEC administered via inhalation (IH) may convert AF rapidly at relatively low doses. Thus, FLEC-IH could be effective at low doses and shorten the time to cardioversion to minutes without requiring emergency room visits.
Flecainide (FLEC) is effective for cardioversion of recentonset atrial fibrillation (AF). In dogs and pigs intratracheal instillation of FLEC is effective in terminating episodes of AF within minutes. The present study is part of a drug development program to use inhaled (IH) of FLEC to cardiovert paroxysmal AF. In this open-labeled 2-period crossover study, we compared the effects of FLEC administered via IV and oral IH on QRS, and PR interval duration, heart rate (HR), blood pressure (BP), and FLEC plasma levels.