Cited by 91Atrial Fibrillation Management and OutcomesCardiac electrophysiology and arrhythmiasCardiac Arrhythmias and Treatments

Self-terminating AF depends on electrical remodeling while persistent AF depends on additional structural changes in a rapid atrially paced sheep model

Anné, Wim, Willems, Rik, Holemans, Patricia, Beckers, Frank, Roskams, Tania, Lenaerts, Ilse, Ector, Hugo, Heidbüchel, Hein·2007·Journal of Molecular and Cellular Cardiology

Abstract

The development of atrial fibrillation (AF) is associated with electrical and structural remodeling. The aim of this study was to assess the contribution of electrical and structural remodeling to the development of AF in a rapid atrially paced ovine model with and without His bundle ablation and to determine the role of the angiotensin pathway and matrix metalloproteinases in this process. Thirty-five sheep were rapidly paced in the atrium and were randomized to undergo His bundle ablation (HBA) (21 sheep; HBA sheep) or not (14 sheep; non-HBA sheep). After HBA the ventricles were paced at 80 bpm. Both groups were subdivided to receive active treatment (quinapril+losartan) or placebo. Sheep were followed for 15 weeks. Inducible AF was defined as a rapid irregular atrial rhythm lasting >1 min. Inducible AF was considered to be persistent if during further follow-up no sinus rhythm (SR) was documented anymore. The inducibility of AF with atrial tachypacing was not different between the 4 groups. On the other hand, non-HBA sheep developed persistent AF significantly earlier than HBA sheep (p=0.028). They had elevated ventricular rates, diminished atrial MMP-2, increased TIMP-2 expression, and more extensive atrial fibrosis. Active treatment in these sheep significantly lowered AT-II (p=0.018), prevented atrial fibrogenesis (p<0.001) and slowed the development of persistent AF (p=0.049). Electrical remodeling is sufficient to induce AF, while structural changes are needed for persistent AF. Fibrosis development in our model is the result of an increased expression of AT-II in combination with changes in MMP expression. Inhibition of the angiotensin pathway suppresses atrial fibrosis and the development of persistent AF.

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Crossref · 10.1016/j.yjmcc.2007.05.010

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  • A number of observational studies have demonstrated the association between female sex and risk of AF-related stroke and thromboembolism.

    “A number of observational studies have demonstrated the association between female sex and risk of AF-related stroke and thromboembolism (Supplementary Table S6).”

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Authors
Anné, W., Willems, R., Holemans, P., Beckers, F., Roskams, T., Lenaerts, I., Ector, H., & Heidbüchel, H.
Affiliations
Universitair Ziekenhuis Leuven (BE)
Corresponding author
Heidbüchel, Hein
Venue
Journal of Molecular and Cellular Cardiology
Publisher
Elsevier BV
Published
2007-08
Volume
43
Issue
2
Pages
148-158
ISSN
0022-2828 (ISSN-L)
OpenAlex
W2007593268
Cited by
91
References
30
Citations by year
2026: 2 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 7 · 2017: 6 · 2016: 6 · 2015: 9 · 2014: 5 · 2013: 8 · 2012: 5
FWCI
3.51
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Molecular and Cellular Cardiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Atrial Fibrillation Management and Outcomes
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
Keywords
atrial fibrillation, electrical remodeling, structural remodeling, atrial fibrosis, His bundle ablation, atrial tachypacing, angiotensin II, angiotensin II receptor blockade, quinapril, losartan, matrix metalloproteinases, MMP-2, TIMP-2, sheep model, persistent atrial fibrillation
MeSH terms
Angiotensin II, Animals, Atrial Fibrillation, Bundle of His, Cardiac Output, Cardiac Pacing, Artificial, Disease Models, Animal, Female, Refractory Period, Electrophysiological, Renin-Angiotensin System, Sheep, Time Factors, Tissue Inhibitor of Metalloproteinases, Matrix Metalloproteinases, Myocytes, Cardiac, Kaplan-Meier Estimate

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