Adriamycin and daunomycin dose-dependent effects upon contractions of isolated rat myocytes

Chemotherapeutic usefulness of adriamycin (ADR) and daunomycin (DAU), members of a large class of antitumor anthracyclines, is limited by a unique cardiotoxicity. Using spontaneously beating isolated myocytes from adult rat hearts, we have observed a relatively unique effect of these agents upon maximal contraction times. ADR and DAU induce cessation of beating in an identical dose-dependent manner, while two related anthracyclines exhibit similar inhibitory effects but at different concentrations. Other cytotoxic and antitumor agents tested failed to significantly affect maximal contraction times. This system may be useful in the evaluation of anthracycline analogs for cardiotoxic potential relative to ADR and DAU, as well as in studying the mechanisms of that toxicity. It may also prove useful in selective examination of the direct effects of other agents upon myocardial cells.