Acute regional left atrial ischemia causes acceleration of atrial drivers during atrial fibrillation

Heart Rhythm. 2013 Jun;10(6):901-9. doi: 10.1016/j.hrthm.2013.02.023. Epub 2013 Feb 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Fibrillation / physiopathology*
  • Disease Models, Animal
  • Electrophysiologic Techniques, Cardiac
  • Glyburide / pharmacology
  • Heart Atria / physiopathology*
  • In Vitro Techniques
  • Myocardial Ischemia / physiopathology*
  • Sheep
  • Voltage-Sensitive Dye Imaging


  • Glyburide