Evaluation of cardiac effects of the new antineoplastic drug - Dimethoxybenfluron - in the rabbit

Cardiotoxicity ranks among the most serious adverse effects of some cytosta tics. The cardiac effects of repeated Lv. administration of a new antineopl astic agent, dimethoxybenfluron (once a week, 10 administrations), were inv estigated in rabbits with respect to cardiac function and the release of ca rdiac troponin T (cTnT). Different doses of dimethoxybenfluron were adminis tered to two groups of animals (12 mg/kg; n=7 and 24 mg/kg; n=6) and compar ed with either a control group (saline 1 ml/kg; n=6) or a group with experi mentally induced cardiomyopathy (daunorubicin 50 mg/m(2); n=13). In daunoru bicin-induced cardiomyopathy, cTnT levels in animals with premature deaths were significantly higher (0.31 +/-0.11 mug/l) in comparison with the survi ving animals (0.04 +/-0.03 mug/l). However, cardiac TnT levels after the ad ministration of dimethoxybenfluron in both doses were within the physiologi cal range (lower than 0.1 mug/l) during the whole experiment as it was in t he control group. The lack of cardiotoxicity of this new antineoplastic dru g was supported by the absence of alterations in PEP:LVET ratio, left ventr icle dP/dt(max) or histological heart examination as well as by the fact th at no premature death of animals occurred following repeated administration of dimethoxybenfluron. It is possible to conclude that no signs of cardiot oxicity were observed following repeated i.v. administration of dimethoxybe nfluron.