Bovine model of doxorubicin-induced cardiomyopathy.
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 (n = 8) were used. Four animals rece...
| Published in: | Journal of Biomedicine & Biotechnology pp. 758736 - 758737 |
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| Main Authors: | , , , , , |
| Format: | research Journal Article |
| Published: |
Wiley-Blackwell
2011
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=104531512&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 104531512 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 11107243 137K jtl: Journal of Biomedicine & Biotechnology issn: 11107243 maglogo: N pubinfo: dt: 2011 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 104531512 104531512 2011456923 NLM21253525 PMC3018676 104531512 ppf: 758736 ppct: 1 formats: fmt: @attributes: type: P tig: atl: Bovine model of doxorubicin-induced cardiomyopathy. aug: au: Bartoli, Carlo R Brittian, Kenneth R Giridharan, Guruprasad A Koenig, Steven C Hamid, Tariq Prabhu, Sumanth D affil: Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202, USA. sug: subj: Myocardial Diseases Chemically Induced Myocardial Diseases Pathology Models, Biological Animals Apoptosis Myocardial Diseases Physiopathology Myocardial Diseases Ultrasonography Cattle Coronary Circulation Physiology Doxorubicin Epinephrine Blood Fibrosis Genes Hemodynamics Physiology Male Myocardium Metabolism Myocardium Pathology Cells Pathology Norepinephrine Blood RNA RNA Metabolism Male ab: 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 (n = 8) 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 (P < 0.05) 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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