Drug inhibition of circulatory response to endotoxin in dogs

¹ Department of Internal Medicine, University of Utah College of Medicine, Salt Lake City, Utah

The effect of combined pretreatment with a drug that inhibits the synthesis of serotonin, alpha-methyl 3,4-dihydroxyphenylalanine, and an antihistamine, promethazine hydrochloride, on the hemodynamic response to E. coli endotoxin was studied in a group of six dogs. Compared with the characteristic endotoxin response obtained in six control experiments, pretreated animals given endotoxin demonstrated significantly less elevation of pulmonary artery (PAP) and portal venous (PVP) pressures, and less striking fall in systemic arterial pressure (SAP) and cardiac output. Considering the average maximum changes alone, expressed as percentage of preendotoxin base-line values, in the control vs. pretreated groups, respectively, results were as follows: SAP, 36 vs. 84%; cardiac output, 31 vs. 66%; PAP, 162 vs. 118%; PVP, 338 vs. 186%. This investigation lends additional support to the concept that many of the cardiovascular effects of endotoxin are mediated through the release of vasoactive agents such as histamine and serotonin.