Glucose kinetics and body temperature after lethal and nonlethal doses of endotoxin

Rats were injected with doses of endotoxin ranging from 1,000 [lethal dose ~ 50% (LD₅₀)] to 0.01 μg/100 g, and alterations in hemodynamics, glucose kinetics, and body temperature were studied over the subsequent 4 h. Doses of 10 μg/100 g or less were consistently nonlethal over 72 h. Decreases in arterial blood pressure and cardiac output were evident in rats receiving 1,000-10 μg/100 g endotoxin. Doses of endotoxin between 1,000 and 10 μg produced an early hyperlactacidemia evident by 1 h, whereas the lower doses (1 and 0.1 μg) induced elevations that exhibited a delayed temporal response. The rates of glucose appearance (Ra) and disappearance (Rd) were increased early and transiently by the higher doses of endotoxin. Lower doses increased glucose Ra and Rd between 2 and 4 h after endotoxin. A febrile response was elicited by 10, 1, and 0.1 μg/100 g endotoxin, while hypothermia was seen in animals receiving higher doses. Thus high doses of endotoxin induced metabolic and hemodynamic alterations that were temporally associated. Very low nonlethal doses of endotoxin (up to 4 orders of magnitude less than LD₅₀) induced metabolic changes that appeared to be independent of hemodynamic disturbances but were temporally associated with the observed hyperthermia.