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Cancer Chemotherapy and Pharmacology

, Volume 35, Issue 3, pp 257–261 | Cite as

Evaluation of anthracycline cardiotoxicity with the model of isolated, perfused rat heart: comparison of new analogues versus doxorubicin

  • Paul Pouna
  • Simone Bonoron-Adèle
  • Gérard Gouverneur
  • Liliane Tariosse
  • Pierre Besse
  • Jacques Robert
Short Communication Anthracyclines, Cardiotoxicity, Islated Perfused Rat Liver

Abstract

We have compared the cardiotixicity of 3 anthracyclines in a model of isolated perfused rat heart using the Langendorff technique. The contractile state and ventricular compliance were studied. Doxorubicin, epirubicin and pirarubicin were perfused at concentrations of 10−6 and 10−5 M during 70 min. The cardiac accumulation of the drugs was studied by HPLC. No significant alteration of cardiac functional parameters was observed at 10−6 M. At 10−5 M, epirubicin produced a significantly greater alteration of cardiac contractility than doxorubicin, whereas pirarubicin exerted first an inotropic effect followed by a recovery to initial values at the 60th min. Anthracycline accumulation in the heart was dose-dependent; epirubicin accumulated to a 30% greater extent than doxorubicin and pirarubicin heart concentrations were 4–5 times higher than those of doxorubicin at the end of the perfusion. These results suggest that doxorubicin and epirubicin have the same intrinsic cardiac toxicity, and that their distinct clinical cardiotoxicity must be explained by pharmacokinetic differences, whereas pirarubicin is much less cardiotoxic than the other anthracyclines because of different pharmacodynamic properties.

Key words

Anthracyclines Cardiotoxicity Isolated perfused rat heart 

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Paul Pouna
    • 1
  • Simone Bonoron-Adèle
    • 2
  • Gérard Gouverneur
    • 2
  • Liliane Tariosse
    • 2
  • Pierre Besse
    • 2
  • Jacques Robert
    • 1
    • 3
  1. 1.Department of Medical Biochemistry and Molecular BiologyUniversity of Bordeaux IIBordeauxFrance
  2. 2.INSERM U8Hôpital Haut-LévêquePessacFrance
  3. 3.Fondation BergoniéBordeaux-cedexFrance

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