Abstract 11534: Activation of ATP-sensitive K+ Channels Favors Initiation and Acceleration of Ischemia-related Atrial Fibrillation
Introduction: Atrial ischemia has been recognized as a pathogenic factor predisposing to atrial fibrillation (AF). However, underlying mechanisms of AF initiation and maintenance remain to be clarified. Using a novel ovine model of acute regional left atrial ischemia (LAI), we hypothesized that an increase in ATP-sensitive K+ channels (KATP) conductance set the stage for AF initiation and maintenance.
Methods: In isolated sheep hearts, LAI was maintained for 90 min. by selective injection of microspheres into the left anterior atrial artery, in the absence (n=10, group-1), or in the presence (n=4, group-2) of the IKATP channel blocker glibenclamide 10 µM. Optical mapping movies (2 CCD cameras, DI-4-ANEPPS) were recorded simultaneously from the epicardial surfaces of either atrium to examine action potential and AF dynamics.
Results: Spontaneous AF occurred in 6/10 hearts in group-1 after 49±33 min LAI (Fig. A), and in only one heart in group-2 (1/4 hearts). Maximal dominant frequency (DFmax) in non-ischemic zone (NIZ) during AF largely increased after LAI compared with baseline (14.2±5.8 vs. 7.3±2.7 Hz, n=9, p<0.05); In the ischemic zone (IZ), however, DFmax was unchanged (7.7±1.2 vs. 7.1±2.0 Hz, n.s). In group-2, LAI did not yield DFmax changes: 6.6±0.3 vs. 5.9±1.3 Hz in NIZ and 8.0±2.0 vs. 8.1±2.0 Hz in IZ (n=3, n.s.). LAI-related AF dynamics was characterized by iterations of spontaneous focal discharges and rotors predominantly locating at the IZ-NIZ border zone (Fig. B). Action potential duration (APD) under constant stimulation in group-1 was shortened by LAI not only in IZ but also in NIZ (by 21-27 %). Conduction velocity decreased by 40.0±20.1% in IZ, whereas was unaffected in NIZ. In group-2, LAI shortened APD in IZ, but not in NIZ.
Conclusions:Following an increase in atrial KATPs conductance and APD reduction, 90-minute LAI leads to spontaneous AF episodes maintained by both spontaneous focal discharges and reentrant circuits located at the IZ border zone.
- © 2012 by American Heart Association, Inc.