Use of detergent to prevent initial responses to endotoxin in horses

Objective - To determine whether a detergent can prevent most of the early effects of IV infusion with Escherichia coli endotoxin (<100 ng/kg of body weight) in horses: marked pulmonary hypertension, acute leukopenia, and fever. Animals - 8 healthy adult horses (4 male, 4 female), 415 to 615 kg. Design and Procedure - Control and detergent experiments were performed in each horse while it was awake but sedated. In control experiments, 10 to 100 ng of E coli endotoxin/kg was given. In detergent experiments, 100 mg of detergent/kg was given 1 hour before injecting endotoxin, similar to the control experiments. Results - In control experiments, pulmonary arterial pressure increased transiently over 40 minutes by 33 ± 8 mm of Hg (mean ± SD; P < 0.001), then returned to baseline. Circulating leukocytes decreased to 47 ± 19% (P < 0.02) of baseline by 1 hour after endotoxin, then increased above baseline by 6 hours. Rectal temperature increased by 0.7 ± 0.4 C (P < 0.01). In detergent experiments, the increase in pulmonary arterial pressure was much less than that in the control experiments (8 ± 7 mm of Hg; P < 0.001). Circulating leukocytes did not decrease, and the increase in rectal temperature after endotoxin was blocked. Conclusions - This attenuation of the response to endotoxin may occur because the normal steps in the response of pulmonary intravascular macrophages (ie, endocytosis of endotoxin and subsequent release of inflammatory mediators) are altered by the detergent. This low-technology, inexpensive, and safe treatment could be an important new clinical tool for veterinarians in combating endotoxemia.