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Updated: May 19, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Doxorubicin induced dilated cardiomyopathy in a rabbit model: an update
Fábio N Gava1, Evandro Zacché, Edna M G Ortiz
1Division of Veterinary Cardiology, São Paulo State University, Jaboticabal, São Paulo, Brazil. fabiocardiovet@ig.com.br
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 2 mg/kg once a week). Twenty rabbits were treated with doxorubicin in two different doses for 6 weeks 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 2 mg/kg once a week. A significant reduction in systolic function was present in animals treated with DOX after 6 weeks, 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 1 mg/kg twice a week for only 6 weeks is safe and sufficient to induce DCM in rabbits.
Insights
Doxorubicin (DOX) can induce dilated cardiomyopathy (DCM) in rabbits. A dose of 1mg/kg twice weekly for 6 weeks safely and effectively caused DCM, aiding research into heart dysfunction.
Area of Science:
- Cardiology
- Pharmacology
- Toxicology
Background:
- Dilated cardiomyopathy (DCM) is a severe heart condition with poor prognosis.
- Developing reliable animal models is crucial for studying DCM and testing new therapies, including stem cell treatments.
- Doxorubicin (DOX), a common chemotherapy drug, is known for its cumulative cardiotoxicity, potentially leading to DCM.
Purpose of the Study:
- To investigate the development of systolic dysfunction in rabbits treated with two different doses of doxorubicin (DOX).
- To establish a safe and effective rabbit model for inducing DCM for further research.
Main Methods:
- Twenty rabbits received DOX at either 1mg/kg twice weekly or 2mg/kg once weekly for 6 weeks.
- A control group received NaCl 0.9%.
- Echocardiography assessed systolic function, while histological analysis and scanning electron microscopy examined myocardial damage in the left ventricle (LV), interventricular septum (IVS), and right ventricle (RV).
Main Results:
- The higher DOX dose (2mg/kg weekly) resulted in a high mortality rate.
- DOX-treated rabbits showed significantly reduced systolic function (decreased ejection fraction and shortening fraction) after 6 weeks.
- Histological and electron microscopy revealed myocardial damage, including vacuolization, granulation, necrosis, and fibrosis in the LV, IVS, and RV.
Conclusions:
- Doxorubicin administration induces DCM-like changes in the LV, IVS, and RV of rabbits.
- The dose of 1mg/kg twice weekly for 6 weeks is sufficient to induce DCM safely and effectively in rabbits, providing a viable model for research.
