title: An acute model for atrial fibrillation arising from a peripheral atrial site: evidence for primary and secondary triggers.
abstract: BACKGROUND
  We previously demonstrated that acetylcholine (Ach) injected into cardiac ganglionated plexi (GP) causes pulmonary vein (PV) ectopy initiating atrial fibrillation (AF).
  
  
  OBJECTIVE
  To determine the effects of Ach applied at non-PV sites.
  
  
  METHODS
  Overall, 54 dogs were anesthetized with Na-pentobarbital. A right and left thoracotomy allowed the placement of multielectrode catheters to record from the superior PVs, mid portion of the atrium and the atrial appendages (AA). A monophasic action potential (MAP) was recorded from the AA. Ach (1, 10, 100 mM) was applied sequentially to the AA.
  
  
  RESULTS
  In 19 of 26 animals, Ach 100 mM on the right (n = 15) or left (n = 4) AA induced focal, sustained AF (>or=10 minutes) with rapid regular firing (cycle length = 37 +/- 7 ms) at the AA. A clamp with teeth placed across the AA caused arrest in the AA. However, AF was sustained only when PV sites adjacent to the GP manifested complex fractionated atrial electrograms (CFAE). Clamping the AA prior to Ach (100 mM) application resulted in focal AF arising at the PVs but not at the AA. When a clamp without teeth was applied prior to Ach application, no AF at either AA or PV site could be induced.
  
  
  CONCLUSIONS
  Isolation of the focal AF at the AA (primary trigger) by clamping caused cessation of activity in the AA, but AF continued due to secondary triggers arising from PVs. The possible mechanism(s) responsible for these findings are discussed, and various ancillary experiments (n = 28) were added to help elucidate mechanisms.
authors.affiliation: Cardiac Arrhythmia Research Institute at the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA. benjamin-scherlag@ouhsc.edu
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Scherlag
authors.forename: Ying-Long
authors.initials: YL
authors.lastname: Hou
authors.forename: Jiaxiong
authors.initials: J
authors.lastname: Lin
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Lu
authors.forename: Soni
authors.initials: S
authors.lastname: Zacharias
authors.forename: Tarun
authors.initials: T
authors.lastname: Dasari
authors.forename: Guodong
authors.initials: G
authors.lastname: Niu
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ghias
authors.forename: Eugene
authors.initials: E
authors.lastname: Patterson
authors.forename: Warren M
authors.initials: WM
authors.lastname: Jackman
authors.forename: Ralph
authors.initials: R
authors.lastname: Lazzara
authors.forename: Sunny S
authors.initials: SS
authors.lastname: Po
mesh_terms: D000109:Acetylcholine; D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D008955:Models, Cardiovascular
chemical_list: D000109:Acetylcholine