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 AF initiation and perpetuation remain unclear. Methods and Results LAI (90-minute ischemia) was obtained in isolated sheep hearts by selectively perfusing microspheres into the left anterior atrial artery. Two CCD cameras and several bipolar electrodes enabled recording from multiple atrial locations: with a dual-camera set-up (Protocol 1, n=10; and 1′, n=4; for bi-atrial or atrio-ventricular camera set-ups respectively), in the presence of propranolol/atropine (1μM) added to the perfusate after LAI (protocol 2, n=3) and after a pre-treatment with glibenclamide 10 μM (protocol 3, n=4). Spontaneous AF occurred in 41.2% (7/17) of the hearts that were in sinus rhythm before LAI. LAI caused APD shortening in both the ischemic (IZ) and non-ischemic (NIZ) zones by 21±8 and 34±13%, respectively (pacing, 5Hz, p<0.05 compared to baseline). Apparent impulse velocity was significantly reduced in the IZ but not in the NIZ (−65±19% and +9±18%, p=0.001 and n.s, respectively). During LAI-related AF, a significant NIZ maximal dominant frequency (DFmax) increase from 7.4±2.5 to 14.0±5.5 Hz; p<0.05, was observed. Glibenclamide, an IKATP channel blocker, averted LAI-related DFmax increase (NIZ: LAI vs Gli, 14.0±5.5 vs. 5.9±1.3 Hz, p<0.05). 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 APD shortening and spontaneous AF maintained by both spontaneous focal discharges and reentrant circuits locating at the IZ border zone.

Impact of coronary artery disease and revascularization on recurrence of atrial fibrillation after catheter ablation: Importance of ischemia in managing atrial fibrillation

“…Previous studies reported the proposed mechanisms of CAD evoking AF . The presence of CAD can cause myocardial ischemia, resulting in impaired relaxation of the left ventricle and leading to higher pressures in the left atrium.…”

“…High left atrial pressures cause ultrastructural and electrical changes in the atrial tissue, potentially forming the arrhythmogenic substrate for AF . Furthermore, the atrial ischemia/infarction resulted in greater atrial electrophysiological changes and propensity for AF forming the dominant substrate for AF . Systemic inflammation and oxidative stress have contributed to atrial remodeling, and the initiation and recurrence of AF .…”

Fibroblast growth factor homologous factors tune arrhythmogenic late NaV1.5 current in calmodulin binding–deficient channels

“…Recorded optical movies were processed using custom software based on PV-WAVE (Precision Visuals — Workstation Analysis and Visualization Environment, Visual Numerics Inc.) ( 64 , 65 ). The background fluorescence was subtracted from each frame, and spatial (5 × 5 pixels) and temporal (9 frames) conical convolution filters were used to increase signal-to-noise ratio.…”

“…Phase movies and phase singularity locations were obtained after Hilbert transformation of the fluorescent signal ( 66 ). Rotational activity of at least 1 cycle was classified as a rotor ( 64 ).…”

Dynamics of propagation patterns and anti-arrhythmic mechanisms during atrial fibrillation

“…When these small re-entrant circuits are situated within the atrial wall they may appear as repetitive breakthroughs. 110,111 Rotors have been observed in experimental studies in isolated sheep hearts and were originally visualized with optical mapping. [112][113][114] Based on such studies it has been proposed that rotors are sources of high frequency that thereby drive AF.…”