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Type: Journal article
Title: An ovine model of toxic, nonischemic cardiomyopathy-assessment by cardiac magnetic resonance imaging
Author: Psaltis, P.
Carbone, A.
Nelson, A.
Lau, D.
Manavis, J.
Finnie, J.
Teo, K.
Mackenzie, L.
Sanders, P.
Gronthos, S.
Zannettino, A.
Worthley, S.
Citation: Journal of Cardiac Failure, 2008; 14(9):785-795
Publisher: Churchill Livingstone Inc Medical Publishers
Issue Date: 2008
ISSN: 1071-9164
Statement of
Peter J. Psaltis, Angelo Carbone, Adam Nelson, Dennis H. Lau, Jim Manavis, John Finnie, Karen S. Teo, Lorraine Mackenzie, Prashanthan Sanders, Stan Gronthos, Andrew C.W. Zannettino and Stephen G. Worthley
Abstract: BACKGROUND: There is a paucity of published experience investigating novel treatment strategies in preclinical and clinical studies of nonischemic cardiomyopathy. We set out to validate an ovine model of doxorubicin-induced cardiomyopathy, using cardiac magnetic resonance (CMR) to assess cardiac function. METHODS AND RESULTS: Ten Merino sheep (51 +/- 8 kg) underwent intracoronary infusions of doxorubicin (1 mg/kg dose) every 2 weeks. Cardiac magnetic resonance was performed at baseline and at 6 weeks after final doxorubicin dose, along with transthoracic echocardiography, measurement of right heart pressure, and cardiac output. After final CMR examination, heart specimens were harvested for histologic analysis. The total dose of doxorubicin administered per animal was 3.8 +/- 0.5 mg/kg. Two animals died prematurely during the study protocol, with evidence of myocarditis. In the remaining 8 sheep, left ventricular ejection fraction dropped from 46.2 +/- 4.7% to 31.3 +/- 8.5% (P < .001), accompanied by reductions in fractional shortening (31.6 +/- 1.8% baseline versus 18.2 +/- 3.9% final, P < .01), cardiac output (3.8 +/- 0.6 L/min versus 3.0 +/- 0.4 L/min, P < .05) and right ventricular ejection fraction (39.5 +/- 5.6% versus 28.9 +/- 9.6%, P < .05). However, significant end-diastolic dilatation of the left ventricle was not observed. Delayed gadolinium uptake was detected by CMR in 2 sheep, in a typical nonischemic pattern. Widespread, multifocal histologic abnormalities consisted of cardiomyocyte degeneration, vasculopathy, inflammatory infiltrates, and replacement fibrosis. CONCLUSIONS: Moderate-severe cardiac dysfunction was reproducibly achieved through high-dose intracoronary doxorubicin, with acceptable animal mortality. CMR provides a powerful tool for assessing myocardial function, structural remodeling, and viability in such models.
Keywords: Animals; Sheep, Domestic; Cardiomyopathies; Disease Models, Animal; Magnetic Resonance Imaging; Echocardiography
Description: Crown copyright © 2008 Published by Elsevier Inc.
RMID: 0020083575
DOI: 10.1016/j.cardfail.2008.06.449
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