The use of anthracycline antitumour agents (e.g., adriamycin and daunorubicin) is limited by their dose-related cardiotoxicity. The effects of the repeated i.v. administration of daunorubicin (50 mg/m2, once weekly, max. 11 weeks)) were investigated in rabbits in vivo from the point of view of the occurrence of cardiotoxicity and compared with a control group of animals. Noninvasive polygraphic records (in ketamine anaesthesia, 50 mg/kg i.m.) were used for the measurement of systolic time intervals (especially the PEP:LVET ratio) to evaluate the function of the heart. The administration of daunorubicin induced a significant, progressive increase in the PEP:LVET ratio (0.3775-0.9473) and in the PEP:LVETcorr. ratio, as well as a lengthening of the preejection period PEP and a shortening of the left ventricular ejection time LVET without significant changes in the electromechanical systole Q-2. The values in the daunorubicin group were mostly significantly different from the control group of animals. The results of polygraphic records reflect thus a presence of cardiac dysfunction on the basis of daunorubicin-induced cardiomyopathy. It is thus possible to conclude that the results obtained in the study confirm the adequacy of the rabbit model of daunorubicin-induced cardiomyopathy and the methods used in the study.

Department of Pharmacology Faculty of Medicine Charles University

Oxidative stress, redox signaling, and metal chelation in anthracycline cardiotoxicity and pharmacological cardioprotection

Dexrazoxane-afforded protection against chronic anthracycline cardiotoxicity in vivo: effective rescue of cardiomyocytes from apoptotic cell death