Doxorubicin administration in dogs produced profound hemodynamic changes mediated by histamine and catecholamine release, which may contribute to the pathogenesis of anthracycline cardiomyopathy.
We evaluated the acute hemodynamic effects of doxorubicin in the open-chest dog. Doxorubicin at doses of 1-4 mg/kg administered over 2 min produced profound hemodynamic changes that were similar to those produced by histamine. These changes persisted despite administering the drug as a slow infusion. Histamine release in peripheral tissues was documented by a marked increase in venous histamine levels following doxorubicin administration. The heart extracted histamine during a period when arterial levels were increased, as indicated by consistently low coronary sinus/aortic ratios. Secondary catecholamine release occurred in response to histamine and histamine-mediated hemodynamic effects. Immunoreactive prostaglandins E and F were increased in coronary sinus blood beginning 30 min after the initiation of a continuous infusion of doxorubicin, and increased slowly thereafter. H1- and H2-receptor blockade with diphenhydramine and cimetidine prevented the early (2-30 min postinfusion) effects of doxorubicin, and combined histaminergic and adrenergic blockade prevented the late effects. A dose of doxorubicin (1 mg/kg) that released histamine and catecholamines produced primary cardiac effects acutely and a cardiomyopathy when administered chronically. The release of vasoactive substances could be part of the pathogenetic mechanism of anthracycline cardiomyopathy.
Bristow et al. (Mon,) conducted a other in Cardiovascular effects of doxorubicin. Doxorubicin was evaluated on Hemodynamic changes and release of vasoactive substances (histamine, catecholamines, prostaglandins). Doxorubicin administration in dogs produced profound hemodynamic changes mediated by histamine and catecholamine release, which may contribute to the pathogenesis of anthracycline cardiomyopathy.