Cellular Mechanisms of Vagally Mediated Atrial Tachyarrhythmia in Isolated Arterially Perfused Canine Right Atria

INTRODUCTION: Increased vagal tone significantly enhances susceptibility to atrial fibrillation (AF); however, the cellular mechanisms responsible for vagally mediated AF are not completely understood. METHODS AND RESULTS: In 12 isolated arterially perfused canine right atria, high-resolution optical mapping techniques were used to measure action potentials during control conditions, during intracardiac parasympathetic nerve stimulation (IPS; 30 to 50 Hz) as a surrogate for vagal stimulation, and during acetylcholine (ACh) infusion (10 to 30 microM). During steady-state pacing, action potential duration was shorter during ACh infusion (43 +/- 9 msec) than during IPS (78 +/- 7 msec, P < 0.001) or control (129 +/- 5 msec, P < 0.001). In contrast, repolarization gradients were larger during IPS (13 +/- 3 msec/mm) than during ACh infusion (3 +/- 1 msec/mm, P < 0.01) or control (5 +/- 1 msec/mm, P < 0.01). Transmural repolarization gradients were relatively small for each intervention tested. During ACh infusion, atrial tachyarrhythmia (AT) was easily initiated with a single premature stimulus and was associated with a focal pattern of activation (84%). AT also was easily initiated by a single premature stimulus during IPS; however, when repolarization gradients were large, patterns of conduction block and incomplete macroreentry were often observed (64%). Importantly, AT initiation during IPS was associated with focal activity (36%) when repolarization gradients were small. CONCLUSION: In contrast to ACh infusion, IPS generally increased dispersion of repolarization and was often associated with patterns of conduction block and incomplete macroreentry, similar to that associated with in vivo cervical vagal stimulation. However, IPS also was associated with a focal pattern of initiation that was independent of local repolarization gradients. These results suggest that during vagal stimulation, AT initiation does not always depend on repolarization gradients.