Rabbit model for in vivo study of anthracycline-induced heart failure and for the evaluation of protective agents
Language English Country Great Britain, England Media print
Document type Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
15182761
DOI
10.1016/j.ejheart.2003.05.003
PII: S1388984203002083
Knihovny.cz E-resources
- MeSH
- Anthracyclines administration & dosage adverse effects MeSH
- Biomarkers blood MeSH
- Time Factors MeSH
- Daunorubicin administration & dosage adverse effects MeSH
- Echocardiography MeSH
- Erythrocyte Indices drug effects MeSH
- Myocytes, Cardiac drug effects pathology MeSH
- Cardiovascular Agents administration & dosage therapeutic use MeSH
- Rabbits MeSH
- Models, Cardiovascular MeSH
- Disease Models, Animal MeSH
- Myocardium cytology pathology MeSH
- Antibiotics, Antineoplastic administration & dosage adverse effects MeSH
- Razoxane administration & dosage therapeutic use MeSH
- Heart Rate drug effects MeSH
- Heart Ventricles diagnostic imaging drug effects pathology MeSH
- Heart Failure chemically induced mortality physiopathology prevention & control MeSH
- Body Weight drug effects MeSH
- Stroke Volume drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Evaluation Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Anthracyclines MeSH
- Biomarkers MeSH
- Daunorubicin MeSH
- Cardiovascular Agents MeSH
- Antibiotics, Antineoplastic MeSH
- Razoxane MeSH
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/dt(max), dP/dt(min)), 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.
References provided by Crossref.org
Cardiac Troponins are Among Targets of Doxorubicin-Induced Cardiotoxicity in hiPCS-CMs
