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

1990; Wiley; Volume: 66; Issue: 4 Linguagem: Inglês

10.1111/j.1600-0773.1990.tb00751.x

1600-0773

Keld Hermansen, I. M. N. Rasmussen, Henning Schou,

Electron Spin Resonance Studies

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° 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 pD 2 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 E max . Pretreatment with Dox 15 mg/kg intraperitoneally 72 hr previously did not influence the pD 2 but caused a significant increase in the E max of the isoprenaline concentration response curve. The results indicate that Dox in vitro interferes with the β‐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 β‐adrenoceptor system. Further it is concluded that isolated atria from mice may be a useful model for testing cardioactive drugs.