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

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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. © 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

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APA

Šimůnek, T., Klimtová, I., Kaplanová, J., Mazurová, Y., Adamcová, M., Štěrba, M., … Geršl, V. (2004). Rabbit model for in vivo study of anthracycline-induced heart failure and for the evaluation of protective agents. European Journal of Heart Failure, 6(4), 377–387. https://doi.org/10.1016/j.ejheart.2003.05.003

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