title: Acute regional left atrial ischemia causes acceleration of atrial drivers during atrial fibrillation.
abstract: BACKGROUND
  The mechanisms by which acute left atrial ischemia (LAI) leads to atrial fibrillation (AF) initiation and perpetuation remain unclear.
  
  
  OBJECTIVE
  To investigate the electrophysiological mechanisms of AF perpetuation in the presence of regional atrial ischemia.
  
  
  METHODS
  LAI (90-minute ischemia) was obtained in isolated sheep hearts by selectively perfusing microspheres into the left anterior atrial artery. Two charge-coupled device cameras and several bipolar electrodes enabled recording from multiple atrial locations: with a dual-camera setup (protocol 1, n = 10, and protocol 1', n = 4, for biatrial or atrioventricular camera setups, respectively), in the presence of propranolol/atropine (1 μM) added to the perfusate after LAI (protocol 2, n = 3) and after a pretreatment with glibenclamide (10 μM; protocol 3, n = 4).
  
  
  RESULTS
  Spontaneous AF occurred in 41.2% (7 of 17) of the hearts that were in sinus rhythm before LAI. LAI caused action potential duration shortening in both the ischemic (IZ) and nonischemic (NIZ) zones by 21% ± 8% and 34% ± 13%, respectively (pacing, 5 Hz; P<.05 compared to baseline). Apparent impulse velocity was significantly reduced in the IZ but not in the NIZ (-65% ± 19% and 9% ± 18%; P = .001 and NS, respectively). During LAI-related AF, a significant NIZ maximal dominant frequency increase from 7.4 ± 2.5 to 14.0 ± 5.5 Hz (P<.05) was observed. Glibenclamide, an ATP-sensitive potassium current (IKATP) channel blocker, averted LAI-related maximal dominant frequency increase (NIZ: LAI vs glibenclamide 14.0 ± 5.5 Hz vs 5.9 ± 1.3 Hz; P<.05). An interplay between spontaneous focal discharges and rotors, locating at the IZ-NIZ border zone, maintained LAI-related AF.
  
  
  CONCLUSIONS
  LAI leads to an IKATP conductance-dependent action potential duration shortening and spontaneous AF maintained by both spontaneous focal discharges and reentrant circuits locating at the IZ border zone.
authors: Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan 48109-2800, USA.
authors: Masatoshi
authors: M
authors: Yamazaki
authors: Uma Mahesh R
authors: UM
authors: Avula
authors: Krishna
authors: K
authors: Bandaru
authors: Auras
authors: A
authors: Atreya
authors: Venkata Subbarao C
authors: VS
authors: Boppana
authors: Haruo
authors: H
authors: Honjo
authors: Itsuo
authors: I
authors: Kodama
authors: Kaichiro
authors: K
authors: Kamiya
authors: Jérôme
authors: J
authors: Kalifa
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000503:physiopathology*; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D005905:Glyburide / Q000494:pharmacology; D006325:Heart Atria / Q000503:physiopathology*; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000503:physiopathology*; D012756:Sheep; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D005905:Glyburide