Mechanisms of atrial tachyarrhythmias associated with coronary artery occlusion in a chronic canine model

Kunihiro Nishida, Xiao Yan Qi, Reza Wakili, Philippe Comtois, Denis Chartier, Masahide Harada, Yu Ki Iwasaki, Philippe Romeo, Ange Maguy, Dobromir Dobrev, Georghia Michael, Mario Talajic, Stanley Nattel

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Abstract

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 Ca 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 transients and enhanced (by â‰̂73%) Na-Ca exchange current. Spontaneous Ca 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-release events, increased Na-Ca 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.

Original languageEnglish
Pages (from-to)137-146
Number of pages10
JournalCirculation
Volume123
Issue number2
DOIs
Publication statusPublished - 18-01-2011

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Coronary Occlusion
Tachycardia
Canidae
Coronary Vessels
Atrial Fibrillation
Myocardial Infarction
Dogs
Infarction
Coronary Artery Disease
Ischemia
Arteries
Cell Separation
Caffeine
Confocal Microscopy
Adrenergic Agents
Electrocardiography
Electrodes
Thorax
Maintenance

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Nishida, Kunihiro ; Qi, Xiao Yan ; Wakili, Reza ; Comtois, Philippe ; Chartier, Denis ; Harada, Masahide ; Iwasaki, Yu Ki ; Romeo, Philippe ; Maguy, Ange ; Dobrev, Dobromir ; Michael, Georghia ; Talajic, Mario ; Nattel, Stanley. / Mechanisms of atrial tachyarrhythmias associated with coronary artery occlusion in a chronic canine model. In: Circulation. 2011 ; Vol. 123, No. 2. pp. 137-146.
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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. 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 Ca 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 transients and enhanced (by {\^a}‰̂73{\%}) Na-Ca exchange current. Spontaneous Ca 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-release events, increased Na-Ca 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.",
author = "Kunihiro Nishida and Qi, {Xiao Yan} and Reza Wakili and Philippe Comtois and Denis Chartier and Masahide Harada and Iwasaki, {Yu Ki} and Philippe Romeo and Ange Maguy and Dobromir Dobrev and Georghia Michael and Mario Talajic and Stanley Nattel",
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Nishida, K, Qi, XY, Wakili, R, Comtois, P, Chartier, D, Harada, M, Iwasaki, YK, Romeo, P, Maguy, A, Dobrev, D, Michael, G, Talajic, M & Nattel, S 2011, 'Mechanisms of atrial tachyarrhythmias associated with coronary artery occlusion in a chronic canine model', Circulation, vol. 123, no. 2, pp. 137-146. https://doi.org/10.1161/CIRCULATIONAHA.110.972778

Mechanisms of atrial tachyarrhythmias associated with coronary artery occlusion in a chronic canine model. / Nishida, Kunihiro; Qi, Xiao Yan; Wakili, Reza; Comtois, Philippe; Chartier, Denis; Harada, Masahide; Iwasaki, Yu Ki; Romeo, Philippe; Maguy, Ange; Dobrev, Dobromir; Michael, Georghia; Talajic, Mario; Nattel, Stanley.

In: Circulation, Vol. 123, No. 2, 18.01.2011, p. 137-146.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mechanisms of atrial tachyarrhythmias associated with coronary artery occlusion in a chronic canine model

AU - Nishida, Kunihiro

AU - Qi, Xiao Yan

AU - Wakili, Reza

AU - Comtois, Philippe

AU - Chartier, Denis

AU - Harada, Masahide

AU - Iwasaki, Yu Ki

AU - Romeo, Philippe

AU - Maguy, Ange

AU - Dobrev, Dobromir

AU - Michael, Georghia

AU - Talajic, Mario

AU - Nattel, Stanley

PY - 2011/1/18

Y1 - 2011/1/18

N2 - 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 Ca 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 transients and enhanced (by â‰̂73%) Na-Ca exchange current. Spontaneous Ca 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-release events, increased Na-Ca 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.

AB - 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 Ca 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 transients and enhanced (by â‰̂73%) Na-Ca exchange current. Spontaneous Ca 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-release events, increased Na-Ca 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.

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