Acute cardiovascular alterations induced by low doses of adriamycin, rubidazone, and daunorubicin in the anesthetized beagle dog

Iv injections of Adriamycin (0.375-3.0 mg/kg), rubidazone (0.75-6.0 mg/kg), or daunorubicin (0.75-6.0 mg/kg) given within 1 minute produced immediate hypotension in anesthetized beagle dogs. The threshold hypotensive dose for Adriamycin (0.375 mg/kg, 7.5 mg/m2) was lower than that for either rubidazone (0.75 mg/kg) or daunorubicin (1.5 mg/kg). Recovery from hypotension was more rapid after administration of rubidazone or daunorubicin than after Adriamycin. Adriamycin (1.5-3.0 mg/kg) caused respiratory distress and depressed mean arterial pressure an average of 54%-82% for up to 30 minutes. The hypotension was almost eliminated when the Adriamycin (1.5 mg/kg) infusion period was extended to 15 minutes. Significant increases in plasma histamine concentrations, coinciding with the peak hypotensive response, were detected within 1 minute after infusion of either Adriamycin (1.5 mg/kg) or rubidazone (1.5 mg/kg). Similar effects were noted after 6.0 mg/kg of daunorubicin. It appears that the acute cardiovascular effects of the three anthracycline compounds are mediated through release of histamine.