title: Mechanisms of atrial tachyarrhythmias associated with coronary artery occlusion in a chronic canine model.
abstract: BACKGROUND
  Coronary artery disease predisposes to atrial fibrillation (AF), but the effects of chronic atrial ischemia/infarction on AF-related substrates are unknown.
  
  
  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 Ca(2+) 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 Ca(2+) transients and enhanced (by ≈73%) Na(+)-Ca(2+) exchange current. Spontaneous Ca(2+) sparks (confocal microscopy) occurred under β-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 (Ca(2+)-release events, increased Na(+)-Ca(2+) 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.
authors.affiliation: Research Center, Montréal Heart Institute and Université de Montréal, 5000 Belanger Street E, Montréal, Quebec, Canada.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Nishida
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Qi
authors.forename: Reza
authors.initials: R
authors.lastname: Wakili
authors.forename: Philippe
authors.initials: P
authors.lastname: Comtois
authors.forename: Denis
authors.initials: D
authors.lastname: Chartier
authors.forename: Masahide
authors.initials: M
authors.lastname: Harada
authors.forename: Yu-ki
authors.initials: YK
authors.lastname: Iwasaki
authors.forename: Philippe
authors.initials: P
authors.lastname: Romeo
authors.forename: Ange
authors.initials: A
authors.lastname: Maguy
authors.forename: Dobromir
authors.initials: D
authors.lastname: Dobrev
authors.forename: Georghia
authors.initials: G
authors.lastname: Michael
authors.forename: Mario
authors.initials: M
authors.lastname: Talajic
authors.forename: Stanley
authors.initials: S
authors.lastname: Nattel
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D002908:Chronic Disease; D023921:Coronary Stenosis / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism
chemical_list: D019831:Sodium-Calcium Exchanger; D002118:Calcium