The isolated mouse atria as a new model for testing cardioactive drugs with special reference to doxorubicin (Adriamycin).
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.
Hermansen
K
K
Department of Biological Sciences, Pharmacology and Toxicology, Royal Danish School of Pharmacy, Copenhagen O, Denmark.
Rasmussen
I M
IM
Schou
H S
HS
D000818:Animals; D016275:Atrial Function; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008954:Models, Biological; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology
D011943:Receptors, Adrenergic, beta; D004317:Doxorubicin