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.
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: Keryn B Palmer; Nathaniel C Thompson; Peter S Spector; Jérôme Kalifa; Jason H T Bates Journal: J Clin Monit Comput Date: 2014-07-15 Impact factor: 2.502
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Authors: Uma Mahesh R Avula; Haikel Dridi; Bi-Xing Chen; Qi Yuan; Alexander N Katchman; Steven R Reiken; Amar D Desai; Samantha Parsons; Haajra Baksh; Elaine Ma; Parmanand Dasrat; Ruiping Ji; Yejun Lin; Christine Sison; W Jonathan Lederer; Humberto C Joca; Christopher W Ward; Maura Greiser; Andrew R Marks; Steven O Marx; Elaine Y Wan Journal: JCI Insight Date: 2021-10-28
Authors: Jeffrey Abrams; Daniel Roybal; Nourdine Chakouri; Alexander N Katchman; Richard Weinberg; Lin Yang; Bi-Xing Chen; Sergey I Zakharov; Jessica A Hennessey; Uma Mahesh R Avula; Johanna Diaz; Chaojian Wang; Elaine Y Wan; Geoffrey S Pitt; Manu Ben-Johny; Steven O Marx Journal: JCI Insight Date: 2020-10-02