Platinum Complexes-Induced Cardiotoxicity of Isolated, Perfused Rat Heart: Comparison of Pt(II) and Pt(IV) Analogues Versus Cisplatin

We have compared the cardiotoxicity of five platinum complexes in a model of isolated rat heart using the Langendorff technique. These effects were assessed via coronary flow (CF) and cardiac functional parameters. cis-Diamminedichloroplatinum(II) (cisplatin, CDDP), dichloro-(1,2-diaminocyclohexane)platinum(II) (Pt(II)DACHCl2), dichloro-(ethylenediamine)platinum(II) (Pt(II)ENCl2), tetrachloro-(1,2-diaminocyclohexane)platinum(IV) (Pt(IV)DACHCl4) and tetrachloro-(ethylenediamine)platinum(IV) (Pt(II)ENCl4) were perfused at increasing concentrations of 10−8, 10−7, 10−6, 10−5 and 10−4 M during 30 min. In this paper, we report that cisplatin-induced dose-dependent effects on cardiac contractility and coronary flow both manifested as decrease in cardiac contractile force (dP/dt)max, heart rate and significant reduction in CF. Pt(II)ENCl2, Pt(IV)ENCl2 and Pt(IV)DACHCl4 did induce dose-dependent response only in case of CF. Our results could be also important for better understanding dose-dependent side effects of potential metal-based anticancer drugs.