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Journal of Biomedicine and Biotechnology
Volume 2011, Article ID 758736, 11 pages
Research Article

Bovine Model of Doxorubicin-Induced Cardiomyopathy

1MD/PhD Program, Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202, USA
2Cardiovascular Innovation Institute, University of Louisville, Louisville, KY 40202, USA
3Department of Medicine, Institute of Molecular Cardiology, University of Louisville, Louisville, KY 40202, USA
4Department of Bioengineering, University of Louisville, Louisville, KY 40208, USA
5Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202, USA
6Robley Rex VAMC, Louisville, KY 40206, USA

Received 25 August 2010; Revised 29 October 2010; Accepted 16 November 2010

Academic Editor: Andrea Vecchione

Copyright © 2011 Carlo R. Bartoli et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Left ventricular assist devices (LVADs) constitute a recent advance in heart failure (HF) therapeutics. As the rigorous experimental assessment of LVADs in HF requires large animal models, our objective was to develop a bovine model of cardiomyopathy. Male calves ( ) were used. Four animals received 1.2 mg/kg intravenous doxorubicin weekly for seven weeks and four separate animals were studied as controls. Doxorubicin-treated animals were followed with weekly echocardiography. Target LV dysfunction was defined as an ejection fraction ≤35%. Sixty days after initiating doxorubicin, a terminal study was performed to determine hemodynamic, histological, biochemical, and molecular parameters. All four doxorubicin-treated animals exhibited significant ( ) contractile dysfunction, with target LV dysfunction achieved in three animals. Doxorubicin-treated hearts exhibited significantly reduced coronary blood flow and interstitial fibrosis and significantly increased apoptosis and myocyte size. Gene expression of atrial natriuretic factor increased more than 3-fold. Plasma norepinephrine and epinephrine levels were significantly increased early and late during the development of cardiomyopathy, respectively. We conclude that sequential administration of intravenous doxorubicin in calves induces a cardiomyopathy with many phenotypic hallmarks of the failing human heart. This clinically-relevant model may be useful for testing pathophysiologic responses to LVADs in the context of HF.