Bacterial dissemination, rather than translocation, mediates hypermetabolic response in endotoxemic rats

OBJECTIVETo study the pathogenesis of the host response during bacterial translocation, a rat model was designed for prolonged follow-up after injury. DESIGNA prospective, controlled animal study. SETTINGAnimal laboratory. SUBJECTSYoung male Wistar rats. INTERVENTIONSAntibiotic decontamination of rats was performed 4 days before intragastric inoculation with a selected Escherichia coli strain (10 bacteria/kg of body weight). Two days later, the rats received a lipopolysaccharide injection or not (control group) and were observed for 3 days. They were then killed. A reference group (pair-fed healthy animals) was studied in parallel. MEASUREMENTS AND MAIN RESULTSDuring observations, urinary total nitrogen loss and 3-methylhistidine excretion were determined daily. When the rats were killed, mesenteric lymph nodes (MLNs), spleen, and liver were aseptically removed and cultured. Colonies identified as translocated E. coli were counted in each organ. Intracellular amino acid free pools were measured in extensor digitorum longus and anterior tibialis. Endotoxin induces bacterial translocation of bacteria from gut lumen to MLNs (100% vs. 59% in the lipopolysaccharide-untreated control group; p < .05) and dissemination to spleen and liver (65% and 45% of positive cultures after endotoxemia, respectively, vs. 6% and 12% in the control groups). No translocation occurred in the reference group. Evidence for the hypermetabolic response was seen in lipopolysaccharide-treated and infected rats, but protein catabolism was more closely related to the occurrence of bacterial dissemination to spleen and liver than to translocation alone (e.g., the cumulative 3-methylhistidine excretion during the observation period was 4.07 +/- 0.18 [micro sign]mol in uninfected rats, 4.48 +/- 0.29 in rats with positive MLN cultures alone and 6.17 +/- 0.30 in MLN, spleen, or liver infected rats; 1 vs. 2, NS; 3 vs. 1, and 3 vs. 2, p < .05). CONCLUSIONSGut barrier failure is associated with a deep excessive catabolic response in the host. The mechanism by which the metabolic state affects the resistance to infection apparently involves amino acid metabolism. (Crit Care Med 1999; 27:1511-1516)