Mechanisms Of Atrial Tachyarrhythmias Associated With Coronary Artery Occlusion In A Chronic Canine Model

Background-Coronary artery disease predisposes to atrial fibrillation (AF), but the effects of chronic atrial ischemia/infarction on AF-related substrates are unknown.Methods and Results-Regional right atrial myocardial infarction (MI) was created in 40 dogs by ligating an artery that supplies the right atrial free wall and not the ventricles; 35 sham dogs with the same artery isolated but not ligated were controls. Dogs were observed 8 days after MI and subjected to open-chest study, in vitro optical mapping, and/or cell isolation for patch-clamp and Ca2+ imaging on day 8. Holter ECGs showed more spontaneous atrial ectopy in MI dogs (eg, 662+/-281 on day 7 versus 34+/-25 ectopic complexes per day at baseline; 52+/-21 versus 1+/-1 atrial tachycardia episodes per day). Triggered activity was increased in MI border zone cells, which had faster decay of caffeine-evoked Ca2+ transients and enhanced (by approximate to 73%) Na+-Ca2+ exchange current. Spontaneous Ca2+ sparks (confocal microscopy) occurred under beta-adrenergic stimulation in more MI dog cells (66+/-9%) than in control cells (29+/-4%; P<0.01). Burst pacing induced long-lasting AF in MI dogs (1146+/-259 versus 30+/-14 seconds in shams). Increased border zone conduction heterogeneity was confirmed by both bipolar electrode mapping in vivo and optical mapping. Optical mapping demonstrated stable border zone reentry in all 9 MI preparations but in none of 6 shams. Border zone tissue showed increased fibrous tissue content.Conclusions-Chronic atrial ischemia/infarction creates substrates for both spontaneous ectopy (Ca2+-release events, increased Na+-Ca2+ exchange current) and sustained reentry (conduction abnormalities that anchor reentry). Thus, chronic atrial infarction in dogs promotes both AF triggers and the substrate for AF maintenance. These results provide novel insights into potential AF mechanisms in patients with coronary artery disease. (Circulation. 2011;123:137-146.)