The Isolated Mouse Atria as a New Model for Testing Cardioactive Drugs with Special Reference to Doxorubicin (Adriamycin®)

Abstract

Spontaneously beating isolated atria from mice were used as a new in vitro model to characterize the mechanism of the cardiotoxic action of the anthracycline cytostatic doxorubicin (Adriamycin). After stabilization at 28 degrees the atria showed a contractile rate and--force of 284 +/- 31 (S.D.) beats/min. and 49 +/- 6.5 mg. Doxorubicin (Dox) (10(-6)-10(-5) M) had a positive chronotropic action per se and decreased the pD2 for the chronotropic action of isoprenaline in a dose-dependent way. However only the effect of the higher concentration proved statistically significant, a concentration which also caused a marked decrease (63%) of the Emax. Pretreatment with Dox 15 mg/kg intraperitoneally 72 hr previously did not influence the pD2 but caused a significant increase in the Emax of the isoprenaline concentration response curve. The results indicate that Dox in vitro interferes with the beta-adrenoceptor function of isolated mouse atria in an unspecific way and that the subacute cardiotoxicity of Dox in mice is probably not due to interference with the beta-adrenoceptor system. Further it is concluded that isolated atria from mice may be a useful model for testing cardioactive drugs.