Cardiovascular and Respiratory Effects of Lethal Doses of Histamine and Compound 48/80 in Rabbits.

Abstract

In rabbits anesthetized with urethane, a lethal dose (2.25 mg/kg intravenously representing 1.5 times LD50) of compound 48/80 produced marked depression of respiration with ensuing blood pressure changes that could be altered by administering artificial respiration. Blood pressure and ecg records in animals artificially respired soon after receiving 4.5 mg/kg of 48/80 revealed no evidence of adverse effects on the vascular system or on cardiac rate and rhythm. Under similar conditions, however, histamine phosphate (1.0 mgAg) produced a prompt and profound fall in blood pressure, marked changes in cardiac rate and rhythm and death despite artificial respiration. The histamine effect appears to be primarily on the cardiovascular system. The lethal action of 48/80 in rabbits is apparently not mediated by release of endogenous histamine since large doses do not elicit histamine-like responses.