Cardiovascular effects of doxorubicin

1. Doxorubicin dose-dependently increased the cardiac contractility of isolated frog heart within the dose-range of 1.0 to 10.0 x 10(-7) M and dose-dependently increased the cardiac output of frog heart in situ with a dose-range between 10(-7) and 10(-5) M. 2. The results of the in situ investigation, using cardiac output as the index of cardiac contractility, were in agreement with the in vitro results. The positive inotropic effects of doxorubicin climaxed around 10(-5) M beyond which there was a dose-dependent decreased in contractility. 3. Haloperidol (10(-6) M), a dopaminergic receptor blocker, and propranolol (10(-8) M), a beta-adrenergic blocker, did not block the positive inotropic effects of doxorubicin. 4. These results provide sufficient basis to suggest that doxorubicin is acting on the isolated amphibian heart through a mechanism which is not associated with beta-adrenergic and/or dopaminergic receptors.