An assessment of plasma histamine concentrations during documented endotoxic shock

Recent reviews of the literature involving histamine release during sepsis and endotoxemia have reported that the majority of the studies are inconclusive due to inadequate assays or experimental protocols. In a controlled experimental setting we have employed a specific and sensitive radioenzymatic assay to determine plasma histamine concentrations temporally during documented endotoxin-induced shock in the conscious rat. Cardiovascular and metabolic measurements for the control group (n=7) were normal during the study period. Endotoxin (n=8, LD/90-24 hrs.) induced an early transient hypotensive episode and increase in systemic vascular resistance and a sustained decrease in cardiac index and central venous pressure and increase in heart and respiratory rates. Hypoglycemia and hyperlacticemia were present at the end of the four-hour study period. The small intestine was severely hemorrhaged in all animals given endotoxin. Histamine concentrations for the control group were unchanged throughout the study period. Contrary to previous reports, this model of endotoxemia revealed unchanging histamine concentrations during the first 30 minutes which were temporally coincident with the characteristic early hypotensive episode evoked by endotoxin. The histamine concentrations at 60 and 240 minutes following endotoxin were increased two and three-fold, respectively, compared to the control group. Three of the 8 rats given endotoxin died before four hours; histamine concentrations in plasma taken when death appeared certain were 42, 91, and 174, compared to the control value of approximately 8 ng/ml. There was no clear association of the increases in plasma histamine with any of the parameters measured in this study; however, established histamine effects may have been masked by the pre-existing effects of other mediators known to be active during endotoxemia. In separate groups of animals endotoxin (n=5) elicited early increases in plasma concentrations of norepinephrine (5-fold) and epinephrine (8-fold) that remained elevated for the 4-hour study period while the control group (n=4) remained stable. This study establishes that a) plasma histamine concentrations are increased during endotoxemia, b) plasma histamine is not elevated during the initial hypotension episode following endotoxin, c) plasma histamine increases during the progression of endotoxic shock, and d) plasma histamine concentrations are extremely high prior to death.NIH guidelines for the use of experimental animals were strictly adhered to throughout this study.