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European Journal of Heart Failure 2004 6(4):377-387; doi:10.1016/j.ejheart.2003.05.003
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© 2004 European Society of Cardiology

Rabbit model for in vivo study of anthracycline-induced heart failure and for the evaluation of protective agents

Tomás Simuneka,*, Ivona Klimtováa, Jana Kaplanováb, Yvona Mazurovác, Michaela Adamcovác, Martin Sterbac, Radomír Hrdinaa and Vladimír Gerslc

a Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
b University Teaching Hospital in Hradec Králové Hradec Králové, Czech Republic
c Faculty of Medicine in Hradec Králové Hradec Králové, Czech Republic

* Corresponding author. Tel.: +420-49-5067295; fax: +420-49-5514373. E-mail address: simunekt{at}faf.cuni.cz


  Abstract

Background: Cardiac toxicity associated with chronic administration of anthracycline (ANT) antibiotics represents a serious complication of their use in anticancer chemotherapy, but can also serve as a useful experimental model of cardiomyopathy and congestive heart failure.

Aims: In this study, a model of chronic ANT cardiotoxicity induced by repeated i.v. daunorubicin (DAU) administration to rabbits was tested.

Methods: Three groups of animals were used: (1) control group—10 animals received i.v. saline; (2) 11 animals received DAU (3 mg/kg, i.v.); (3) 5 animals received the model cardioprotective agent dexrazoxane (DEX, 60 mg/kg, i.p.), 30 min prior to DAU. All substances were administered once weekly, for 10 weeks. The DAU-induced heart damage and protective action of DEX were determined and quantitated with the use of histopathology, invasive haemodynamic measurements (e.g. left ventricular pressure changes—dP/dtmax, dP/dtmin), non-invasive systolic function examinations (left ventricular ejection fraction, PEP/LVET index) and biochemical analysis of cardiac troponin T plasma concentrations.

Results: All the employed methods showed unambiguously pronounced heart impairment in the DAU group, with the development of both systolic and diastolic heart failure, as well as significant reduction of DAU-cardiotoxicity in DEX-pretreated animals. Other toxicities were acceptable.

Conclusion: The presented model has been approved to be consistent and reliable and it can serve as a basis for future determinations and comparisons of chronic cardiotoxic effects of various drugs, as well as for the evaluation of potential cardioprotectants.

Key Words: Daunorubicin • Cardiotoxicity • Cardiomyopathy • Heart failure • Animal model • Dexrazoxane

Received December 5, 2002; Revised February 28, 2003; Accepted May 1, 2003


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