[Evaluation of the dose of endotoxin to produce endotoxin shock models in dogs]

Intravenous bolus administration of purified endotoxin (ET) is one of the most popular methods of producing experimental ET shock. In an attempt to evaluate the dose of ET in these experimental models, the kinetics of ET was assessed in various doses (1-0.002 mg.kg-1), and dose response study was performed, measuring chronological changes in hemodynamic (mean arterial pressure & cardiac output) and hematological (leucocyte & platelet counts) parameters. It was demonstrated that plasma ET concentrations were sustained extraordinarily high (greater than 5000 pg.ml-1) in doses of 0.2-1 mg.kg-1 during the observation period of several hours, while they were measurable in doses of 0.02 and 0.002 mg.kg-1, showing a biphasic decrease pattern after ET administration. In particular, plasma ET levels of low dose group (0.002 mg.kg-1) were similar to those of clinical gram negative septic patients. We conclude that the empirically used ET doses of more than 1 mg.kg-1 produce extremely severe endotoxemia and that milder degree of ET shock models produced by low dose of ET (0.002 mg.kg-1) would be more applicable for a pathophysiological study of ET shock.