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European Heart Journal Advance Access originally published online on November 10, 2006
European Heart Journal 2006 27(24):3045-3056; doi:10.1093/eurheartj/ehl360
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© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Atrial electrical and structural abnormalities in an ovine model of chronic blood pressure elevation after prenatal corticosteroid exposure: implications for development of atrial fibrillation

Peter M. Kistler1, Prashanthan Sanders1, Miodrag Dodic2, Steven J. Spence1, Chrishan S. Samuel2, ChongXin Zhao2, Jennifer A. Charles3, Glenn A. Edwards3 and Jonathan M. Kalman1,*

1 Department of Cardiology, Royal Melbourne Hospital, Melbourne 3050, Australia
2 Howard Florey Institute, The University of Melbourne, Melbourne, Australia
3 Department of Veterinary Science, The University of Melbourne, Melbourne, Australia

Received 24 March 2006; revised 24 September 2006; accepted 19 October 2006; online publish-ahead-of-print 10 November 2006.

* Corresponding author. Tel: +61 3 93495400; fax: +61 3 93495411. E-mail address: jon.kalman{at}mh.org.au

See page 2919 for the editorial comment on this article (doi:10.1093/eurheartj/ehl374)

Aims Elevated blood pressure (EBP) is the most prevalent and potentially modifiable risk factor for AF, yet little is known of its atrial effects. We aimed to characterize the atrial electrical and structural changes in a chronic ovine model of EBP after prenatal corticosteroid exposure.

Methods and results Twelve sheep with chronically EBP (mean arterial pressure 94±3 mmHg) and six controls (71±4 mmHg, P<0.01) underwent acute open chest electrophysiologic and pathologic studies. We measured refractoriness at the atrial appendages at 3 cycle lengths (CL); conduction velocities at Bachmann's bundle, both atrial appendages and free walls at 4 CLs; conduction heterogeneity; atrial wavelength and AF duration. We performed light microscopy (LM) and electron microscopy (EM) and collagen and apoptosis studies. EBP was associated with widespread conduction abnormalities, shortening of atrial wavelength, and increased AF. There was no significant change in refractoriness. LM demonstrated atrial myocyte hypertrophy and myolysis in all EBP sheep and focal scarring in six. EM demonstrated mitochondrial and nuclear enlargement and increased collagen fibrils in EBP sheep, findings not present in any controls. Atrial collagen and apoptosis were increased in EBP animals.

Conclusion This study demonstrates that chronically, EBP is associated with significant atrial electrical and structural remodelling. These changes may explain the increased propensity to atrial arrhythmias observed with long-standing EBP.

Key Words: Hypertension • Atrium • Atrial fibrillation • Apoptosis


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