The effect of repeated i.v. administration (once weekly, 12 administrations) of a new
antineoplastic agent,
Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5, 11-dioxo-5,6-dihydro-11 H-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 evaluate the function of the heart. The morphological changes of the heart were evaluated after the death of animals. There were no significant changes found in the ratio of the pre-ejection period/left ventricular ejection time (PEP: LVET ratio) after administration of
Oracin (values between 0.3080 and 0.3310) or in the control group (values between 0.3425 and 0.3885). The administration of
daunorubicin induced a significant, progressive increase in the PEP: LVET ratio (0.3775-0.9473), which was significantly different both from the
Oracin-treated and the control group of animals. Histological examination of the hearts from the control group revealed normal structure of the myocardium including minute changes (dispersed cardiomyocytes with intensively eosinophilic cytoplasm, and several single cells with degenerated myofibrils) similar to the normal changes in muscle tissue. A very similar scenario was found in the
Oracin group with the exception of one case where a slightly higher number of degenerated and necrotic cells was occurring. Administration of
daunorubicin resulted in severe dispersed damage of the myocardium (myocytolysis with subsequent interstitial
fibrosis), the changes being markedly different from those of the
Oracin treatment and the control group. On the basis of our results it is possible to conclude that the administration of
Oracin (10 mg/kg i.v.) did not induce signs of
cardiotoxicity in rabbits in vivo.