Pacing-Induced Spontaneous Activity in Myocardial Sleeves of Pulmonary Veins After Treatment With Ryanodine

Abstract
Background— Recent clinical electrophysiology studies and successful results of radiofrequency catheter ablation therapy suggest that high-frequency focal activity in the pulmonary veins (PVs) plays important roles in the initiation and perpetuation of atrial fibrillation, but the mechanisms underlying the focal arrhythmogenic activity are not understood. Methods and Results— Extracellular potential mapping of rabbit right atrial preparations showed that ryanodine (2 μmol/L) caused a shift of the leading pacemaker from the sinoatrial node to an ectopic focus near the right PV-atrium junction. The transmembrane potential recorded from the isolated myocardial sleeve of the right PV showed typical atrial-type action potentials with a stable resting potential under control conditions. Treatment with ryanodine (0.5 to 2 μmol/L) resulted in a depolarization of the resting potential and a development of pacemaker depolarization. These changes were enhanced transiently after an increase in the pacing rate: a self...