TY - JOUR
T1 - An Ovine Model of Toxic, Nonischemic Cardiomyopathy-Assessment by Cardiac Magnetic Resonance Imaging
AU - Psaltis, Peter J.
AU - Carbone, Angelo
AU - Nelson, Adam
AU - Lau, Dennis H.
AU - Manavis, Jim
AU - Finnie, John
AU - Teo, Karen S.
AU - Mackenzie, Lorraine
AU - Sanders, Prashanthan
AU - Gronthos, Stan
AU - Zannettino, Andrew C W
AU - Worthley, Stephen G.
N1 - Funding Information:
Dr Psaltis is supported by a Postgraduate Medical Scholarship from the National Health and Medical Research Council of Australia and the National Heart Foundation of Australia and a Dawes Scholarship from the Royal Adelaide Hospital. Dr Lau is supported by a Postgraduate Medical Scholarship from the National Health and Medical Research Council of Australia, the Earl Bakken Electrophysiology Scholarship from the University of Adelaide and a Kidney Health Australia Biomedical Research Scholarship. Dr Mackenzie is supported by the Peter Doherty Fellowship, National Health and Medical Research Council of Australia. Dr Sanders is supported by the National Heart Foundation of Australia.
PY - 2008/11
Y1 - 2008/11
N2 - 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. Crown
AB - 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. Crown
KW - Cardiomyopathy
KW - animal model
KW - magnetic resonance imaging
KW - nonischemic
UR - http://www.scopus.com/inward/record.url?scp=55149111422&partnerID=8YFLogxK
U2 - 10.1016/j.cardfail.2008.06.449
DO - 10.1016/j.cardfail.2008.06.449
M3 - Article
C2 - 18995184
AN - SCOPUS:55149111422
SN - 1071-9164
VL - 14
SP - 785
EP - 795
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
IS - 9
ER -