Continuous infusion of endotoxin from an osmotic pump in the conscious, unrestrained rat: a unique model of chronic endotoxemia.

Endotoxin (ET) was administered to conscious, unrestrained rats by continuous intravenous infusion from an Alzet osmotic pump. Delivery of ET was delayed 42 h after surgery by inserting a 100-cm coil of PE-60 tubing between pump and jugular vein. Rats were anorectic following onset of ET delivery; therefore control rats were either fed ad libitum or food-deprived (FD) to match the voluntary consumption of ET rats. Blood was collected from carotid catheters and oxygen consumption determined daily. Body weight, colon temperature, and plasma glucose were similar in ET and FD rats, but ET rats exhibited a transient hyperlactacidemia, progressive leukocytosis, and fall in hematocrit which was not seen in FD rats. Food deprivation resulted in a marked drop in plasma insulin which was not seen in ET rats, despite similar food intake and plasma glucose concentration. Oxygen consumption of ET rats was significantly greater than both fed and FD animals on days 1 and 2 of ET infusion, while mean arterial pressure and heart rate were similar to controls. A unique model of endotoxemia is presented which is characterized by a transient hypermetabolic state, and changes in plasma lactate and insulin levels, white cell count, and hematocrit, which cannot be attributed to food deprivation. The results suggest that ET may be important in the pathogenesis of hypermetabolic sepsis.