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Atrial remodeling and the substrate for atrial fibrillation in rat hearts with elevated afterload

Kim, Shang-Jin; Choisy, Stephanie C.M.; Barman, Palash; Zhang, Haifei; Hancox, Jules C.; Jones, Sandra A.; James, Andrew F.

Authors

Shang-Jin Kim

Stephanie C.M. Choisy

Palash Barman

Haifei Zhang

Jules C. Hancox

Andrew F. James



Abstract

BACKGROUND: Although arterial hypertension and left ventricular hypertrophy are considered good epidemiological indicators of the risk of atrial fibrillation (AF) in patients, the link between elevated afterload and AF remains unclear. We investigated atrial remodeling and the substrate for arrhythmia in a surgical model of elevated afterload in rats. METHODS AND RESULTS: Male Wistar rats (aged 3-4 weeks) were anesthetized and subjected to either partial stenosis of the ascending aorta (AoB) or sham operation (Sham). Experiments were performed on excised hearts 8, 14, and 20 weeks after surgery. Unipolar electrograms were recorded from the left atrial epicardial surface of perfused hearts using a 5×5 electrode array. Cryosections of left atrial tissue were retained for histological and immunocytochemical analyses. Compared to Sham, AoB hearts showed marked left atrial hypertrophy and fibrosis at 14 and 20 weeks postsurgery. The incidence and duration of pacing-induced AF was increased in hearts from AoB rats at 20 weeks postsurgery. The substrate for arrhythmia was associated with reduced vectorial conduction velocity and greater inhomogeneity in conduction but without changes in effective refractory period. Left atrial expression of the gap junction protein, connexin43, was markedly reduced in AoB compared with Sham hearts. CONCLUSIONS: Using a small-animal model, we demonstrate that elevated afterload in the absence of systemic hypertension results in increased inducibility of AF and left atrial remodeling involving fibrosis, altered atrial connexin43 expression, and marked conduction abnormalities.

Journal Article Type Article
Publication Date Oct 1, 2011
Journal CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
Print ISSN 1941-3149
Electronic ISSN 1941-3084
Publisher American Heart Association
Peer Reviewed Peer Reviewed
Volume 4
Issue 5
Pages 761-769
APA6 Citation Kim, S., Choisy, S. C., Barman, P., Zhang, H., Hancox, J. C., Jones, S. A., & James, A. F. (2011). Atrial remodeling and the substrate for atrial fibrillation in rat hearts with elevated afterload. Circulation. Arrhythmia and electrophysiology, 4(5), 761-769. doi:10.1161/CIRCEP.111.964783
DOI https://doi.org/10.1161/CIRCEP.111.964783
Keywords arrhythmia; conduction; connexin43; fibrosis; gap junctions
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