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Doxorubicin induced dilated cardiomyopathy in a rabbit model: An update

Author:
Gava, Fábio N., Zacché, Evandro, Ortiz, Edna M.G., Champion, Tatiana, Bandarra, Marcio B., Vasconcelos, Rosemeri O., Barbosa, José C., Camacho, Aparecido A.
Source:
Research in veterinary science 2013 v.94 no.1 pp. 115-121
ISSN:
0034-5288
Subject:
animal disease models, cardiomyopathy, doxorubicin, echocardiography, fibrosis, histology, mortality, myocardium, necrosis, prognosis, rabbits, scanning electron microscopy, sodium chloride, stem cells, therapeutics
Abstract:
Dilated cardiomyopathy (DCM) is characterized by chamber dilation and cardiac dysfunction. Because of the poor prognosis, models are needed for the investigation of and development of new therapeutic approaches, as well as stem cell therapy. Doxorubicin (DOX), used as chemotherapeutic agent, is reported to be cumulative cardiotoxic causing DCM. The aim of the study was to investigate the onset of systolic dysfunction using echocardiography in rabbits receiving two different doses of DOX (1mg/kg twice a week and 2mg/kg once a week). Twenty rabbits were treated with doxorubicin in two different doses for 6weeks and compared with a control group treated with NaCl 0.9%. The effect of doxorubicin on the myocardium was investigated with histological analysis and scanning electron microscopy of left ventricle (LV), as well as in the interventricular septum (IVS) and right ventricle (RV). The results showed a high mortality rate for rabbits receiving 2mg/kg once a week. A significant reduction in systolic function was present in animals treated with DOX after 6weeks, with decreased ejection fraction and shortening fraction. Histology and electron microscopy revealed vacuolization, intracytoplasmic granulation, necrosis and interstitial fibrosis in LV, as well as in the IVS and RV. Doxorubicin induced changes are present in the LV, RV and IVS, and the administration at the dose of 1mg/kg twice a week for only 6weeks is safe and sufficient to induce DCM in rabbits.
Agid:
1140784