OBJECTIVES: To review the electrophysiologic effects of antiarrhythmic agents in pulmonary veins (PV) sleeve preparations. BACKGROUND: Ectopic activity arising from the PV plays a prominent role in the development of atrial fibrillation. METHODS: Transmembrane action potentials were recorded from canine superfused left superior or inferior PV sleeves using standard microelectrode techniques. Acetylcholine (ACh, 1 µM), isoproterenol (1 µM), high calcium ([Ca2+]o=5.4mM) or a combination was used to induce early or delayed afterdepolarizations (EADs or DADs) and triggered activity. RESULTS: In canine PV sleeves, ranolazine (10 µM) induced a marked use-dependent decrease in Vmax, a rate-dependent abbreviation of action potential duration (APD), but a rate-dependent increase in effective refractory period due to the development of post-repolarization refractoriness and eliminates rate-dependent delayed and late phase 3 early afterdepolarizations (DADs and EADs)-induced triggered activity induced by high calcium, isoproterenol, acetylcholine of their combination together with rapid pacing. Chronic amiodarone induced a prolongation of APD, a marked decrease in Vmax, and prevented the development of DADs and late phase 3 EADs-induced triggered activity. Combination of ranolazine and chronic amiodarone act synergistically to cause potent use-dependent depression of sodium channel-dependent parameters in PV sleeves but not ventricular tissues. CONCLUSIONS: The PV sleeve preparation is a useful model for the study of pharmacologic agents for the treatment of atrial fibrillation. The effectiveness of these agents in arrhythmias induced in PV sleeves may indicate an antiarrhythmic action in eliminating the triggers responsible for AF.