Cardiovascular actions of an experimental antitumor agent, homoharringtonine, in anesthetized dogs

Cardiovascular actions of homoharringtonine, a plant extract currently being tested for clinical efficacy as an antitumor agent, were investigated in anesthetized mongrel dogs. Intravenous administration of homoharringtonine (4 mg/M2) produced significant reductions in heart rate, cardiac output, and arterial blood pressure, while myocardial contractility or total peripheral resistance were not altered. These results suggest that the bradycardia could account for decreases in both cardiac output and blood pressure. In additional experiments performed to evaluate the actions of homoharringtonine on cardiac sympathetic neurotransmission it was discovered that this compound caused significant impairment of the tachycardia elicited during stimulation of cardiac sympathetic nerves. The positive chronotropic effects of either norepinephrine or isoproterenol were not altered by homoharringtonine. In these animals in which both vagi and the right cardioaccelerator nerve were sectioned, the hypotensive and bradycardiac effects were of lesser magnitude than that seen in neurally intact animals. These results show that a dose of homoharringtonine comparable to that used in clinical trials produces hypotension and bradycardia which may result from inhibition of sympathetic nerve function caused by the compound.