title: Rapid and stable re-entry within the pulmonary vein as a mechanism initiating paroxysmal atrial fibrillation.
abstract: OBJECTIVE
  We investigated the hypothesis that re-entrant pulmonary vein (PV) tachycardias may serve as a mechanism for initiating and sustaining paroxysmal atrial fibrillation (PAF).
  
  
  BACKGROUND
  The mechanisms of rapid repetitive discharges from the PV initiating PAF remain incompletely understood. Pulmonary vein myocardial sleeves appear to provide a favorable substrate for re-entry formation.
  
  
  METHODS
  The electrophysiologic properties of canine PV sleeves were investigated using a combination of high-resolution optical mapping (n = 5) and extracellular bipolar and intracellular microelectrode recordings (n = 56) in a superfused PV preparation.
  
  
  RESULTS
  From the left atrium to distal PV, there was progressive shortening of the action potential (AP) duration, reduction in AP and bipolar electrogram amplitude, and depolarization of resting membrane potentials. Sustained PV tachycardias were induced exclusively in the presence of acetylcholine (10(-7) to 10(-6) mol/l, n = 12). Sustained PV tachycardias were rapid (mean cycle length = 93 +/- 15 ms), regular, and capable of induction, termination, and resetting by single extrastimuli. Re-entry as the mechanism underlying PV tachycardias was confirmed by optical mapping (n = 5). Acetylcholine also reduced the slope of the AP restitution curve and suppressed AP alternans (n = 6). Importantly, PV tachycardias exhibited 1:1 conduction into the atrium at short cycle lengths (<100 ms), emphasizing the potential role of re-entrant PV tachycardia in atrial fibrillation.
  
  
  CONCLUSIONS
  Pulmonary veins provide a favorable substrate for re-entry formation. Heterogeneity of the electrophysiologic properties and marked abbreviation of action potential duration and refractoriness by acetylcholine combine to produce rapid and stable re-entrant PV tachycardias. Elevated parasympathetic tone and re-entrant PV tachycardia may serve as a mechanism underlying the perpetuation of PAF.
authors.affiliation: Cardiac Arrhythmia Research Institute, Department of Medicine, Oklahoma City, Oklahoma, USA. sunny-po@ouhsc.edu
authors.forename: Sunny S
authors.initials: SS
authors.lastname: Po
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Tang
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Ning
authors.initials: N
authors.lastname: Geng
authors.forename: Warren M
authors.initials: WM
authors.lastname: Jackman
authors.forename: Benjamin
authors.initials: B
authors.lastname: Scherlag
authors.forename: Ralph
authors.initials: R
authors.lastname: Lazzara
authors.forename: Eugene
authors.initials: E
authors.lastname: Patterson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000503:physiopathology; D008297:Male; D011667:Pulmonary Veins / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D000109:Acetylcholine