Experimental model for paroxysmal atrial fibrillation arising at the pulmonary vein-atrial junctions

Abstract

The mechanism(s) by which pulmonary veins (PVs) become ectopically active and subsequently initiate and sustain atrial fibrillation (AF) remains poorly understood. The purpose of this study was to produce an acute canine model of paroxysmal AF arising from the PVs. In 11 dogs, a thoracotomy was performed and a 26-gauge needle with a polyethylene tube attached was inserted into a fat pad containing autonomic ganglia at the base of the PV. The 11 dogs were divided into two groups: acetylcholine (ACh) 1-10 mM (group I, n = 5) or carbachol (CARB) 1-10 mM (group II, n = 6) injected (0.5 mL) into the fat pad. Within 2 to 5 minutes after injection of parasympathomimetics into the fat pad, a sequence of heart rate slowing, spontaneous premature depolarizations, and spontaneous AF was observed in four of 11 dogs. In seven dogs, single premature extrastimuli easily induced AF. AF was sustained for an average of 10 minutes (ACh) and 38 minutes (CARB), with the shortest AF cycle length seen at the PV-atrial junction adjacent to the fat pad (AF cycle length 75 +/- 41 ms for ACh and 37 +/- 12 ms for CARB). Acute autonomic remodeling produced by injection of parasympathomimetics into the fat pad resulted in spontaneous or easily induced sustained AF with short AF cycle length; the most rapid firing rate was observed in the PV and atria adjacent to the injected fat pad. These findings resemble paroxysmal AF in patients, suggesting that hyperactive autonomic ganglia may be a critical element in patients exhibiting focal AF arising from the PV.