title: Pulmonary Vein Sleeves as a Pharmacologic Model for the Study of Atrial Fibrillation.
abstract: OBJECTIVE
  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.
authors.affiliation: Masonic Medical Research Laboratory, Utica, NY.
authors.forename: Serge
authors.initials: S
authors.lastname: Sicouri
authors.affiliation: Masonic Medical Research Laboratory, Utica, NY.
authors.forename: Charles
authors.initials: C
authors.lastname: Antzelevitch
keywords: Antiarrhythmic drugs; Atrial fibrillation; Electrophysiology; Pharmacology; Pulmonary veins