Changes of the calcium tolerance in anthracycline treated mice

Anthracyclines are effective antineoplastic agents inducing cardiomyopathy as a side effect. The mechanism of the anthracycline cardiotoxicity is not completely understood, but a disturbance of the Ca2+ -homeostasis seems to be involved. In our study we investigated the Ca2+ -tolerance in mice after a single administration of 2 mg/kg violamycin bI (vbI). Isolated hearts were perfused with increasing concentrations of Ca2+ until cardiac arrest. In the hearts of control animals the highest tolerable concentration was about 19 mM. 4 and 8 days after the vbI application 8 and 12 mM Ca2+, respectively, induced cardiac arrest. On the 12th day the Ca2+ tolerance was similar to control organs. 16 and 20 days after the vbI injection the highest tolerable Ca2+ -concentration sank again. On the 24th day the Ca2+ -tolerance was nearly the same as in controls.