ELECTROPHYSIOLOGY OF PULMONARY VEINMYOCARDIAL SLEEVES AND THEIR ROLE IN ATRIALFIBRILLATION

摘要

Recent clinical electrophysiology studies have suggested that ectopic beats originating mainly from the pulmonary veins (PVs) play important roles in the initiation and perpetuation of atrial fibrillation (AF). However, mechanisms underlying arrhythmogenic focal activity in the PVs are not fully understood. We investigated the electrical properties of isolated myocardial sleeves of rabbit PVs by recording the transmembrane potential. Typical atrial-type action potentials were elicited from a stable resting membrane potential in response to stimuli under control conditions. Treatment with low concentrations (0.5-2 u.M) of ryanodine, an inhibitor of carcoplasmic reticulum (SR) Ca~(2+) release channel function, resulted in a depolarization of the resting potential and a development of pacemaker-type diastolic depolarization. These changes were enhanced transiently after an increase in the pacing rate, and self-terminating bursts of repetitive spontaneous action potentials were consistently induced. The pacing-induced activity was suppressed by inhibitors of the SR Ca~(2+) uptake pump, of the sarcolemmal Na7Ca~(2+) exchange, and of Ca~(2+)-dependent Cl' channels and was enhanced by p-adrenergic stimulation, compatible with a mechanism related to Ca~(2+)-sensitive transient inward currents. In normal atrial muscle of the right or left atrial appendage treated with ryanodine, rapid pacing never induced spontaneous activity. Extracellular potential mapping of rabbit atrial preparations showed a pacemaker shift from the sinoatrial node to an ectopic focus close to the PV-atrium junction after treatment with ryanodine (2 uM). These results suggest that PV myocardial sleeves have the potential to generate spontaneous activity and modulation of intracellular Ca~(2+) dynamics may uncover such arrhythmogenic activity.