LACK OF CARDIOTOXICITY OF A NEW ANTINEOPLASTIC AGENT, A SYNTHETIC DERIVATIVE OF INDENOISOCHINOLINE - COMPARISON WITH DAUNORUBICIN IN RABBITS

The effect of repeated i.v. administration (once weekly, 12 administra tions) of a new antineoplastic agent, Oracin thyl)aminoethyl]-5,11-dio xo-5,6-dihydro-11H-indeno [1,2-c]-isochinoline hydrochloride, 10 mg/kg ) and daunorubicin (3 mg/kg) were investigated in rabbits in vivo. The criterion of occurrence of cardiotoxicity was compared with a control group of animals. Noninvasive polygraphic records were used to evalua te the function of the heart, The morphological changes of the heart w ere evaluated after the death of animals. There were no significant ch anges found in the ratio of the pre-ejection period/left ventricular e jection time (PEP:LVET ratio) after administration of Oracin (values b etween 0.3080 and 0.3310) or in the control group (values between 0.34 25 and 0.3885). The administration of daunorubicin induced a significa nt, progressive increase in the PEP:LVET ratio (0.3775-0.9473), which was significantly different both from the Oracin-treated and the contr ol group of animals. Histological examination of the hearts from the c ontrol group revealed normal structure of the myocardium including min ute changes (dispersed cardiomyocytes with intensively eosinophilic cy toplasm, and several single cells with degenerated myofibrils) similar to the normal changes in muscle tissue, A very similar scenario was f ound in the Oracin group with the exception of one case where a slight ly higher number of degenerated and necrotic cells was occurring. Admi nistration of daunorubicin resulted in severe dispersed damage of the myocardium (myocytolysis with subsequent interstitial fibrosis), the c hanges being markedly different from those of the Oracin treatment and the control group. On the basis of our results it is possible to conc lude that the administration of Oracin (10 mg/kg i.v.) did not induce signs of cardiotoxicity in rabbits in vivo.