Influence of promethazine on circulatory response to endotoxin in dogs

Abstract

Histamine has been implicated as an intermediary in the mechanism of experimental endotoxin shock. The effect of pretreatment with an antihistaminic drug, promethazine hydrochloride (PMZ), on the hemodynamic response to E. coli endotoxin was studied in a group of 13 anesthetized dogs. Results were compared with the characteristic effects of endotoxin obtained in six control animals. Parameters that were measured and evaluated for possible effects of pretreatment were as follows: systemic artery, pulmonary artery, and portal vein pressures; cardiac output; heart rate; and calculated systemic and pulmonary resistances. In six animals that received doses of PMZ ranging from 1 to 9 mg/kg, the responses to endotoxin were not significantly different from those in the control group. However, in a group of seven dogs pretreated with a standard dose of 20 mg/kg PMZ, a modified response was demonstrated consisting of significant reduction in the magnitude of early systemic hypotension and portal venous hypertension. Pulmonary hypertension was augmented. The results are consistent with the interpretation that certain circulatory effects of endotoxin are mediated through histamine and that these are partially amenable to selective inhibition by an adequate dose of an antihistaminic agent such as PMZ.