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

Objective: To study the pathogenesis of the host response during bacterial translocation, a rat model was designed for prolonged follow-up after injur y. Design: A prospective, controlled animal study. Setting: Animal laboratory. Subjects: Young male Wistar rats. Interventions: Antibiotic decontamination of rats was performed 4 days befo re intragastric inoculation with a selected Escherichia coli strain (10(10) bacteria/kg of body weight). Two days later, the rats received a lipopolys accharide injection or not (control group) and were observed for 3 days, Th ey were then killed. A reference group (pair-fed healthy animals) was studi ed in parallel. Measurements and Main Results: During observations, urinary total nitrogen loss and 3-methylhistidine excretion were determined daily. When the rats w ere killed, mesenteric lymph nodes (MLNs), spleen, and liver were aseptical ly removed and cultured. Colonies identified as translocated E. coli were c ounted in each organ. Intracellular amino acid free pools were measured in extensor digitorum longus and anterior tibialis, Endotoxin induces bacteria l translocation of bacteria from gut lumen to MLNs (100% vs. 59% in the lip opolysaccharide-untreated control group; p < .05) and dissemination to sple en and liver (65% and 45% of positive cultures after endotoxemia, respectiv ely, vs. 6% and 12% in the control groups). No translocation occurred in th e reference group. Evidence for the hypermetabolic response was seen in lip opolysaccharide-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 e xcretion during the observation period was 4.07 +/- 0.18 mu mol in uninfect ed 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), Conclusions: Gut barrier failure is associated with a deep excessive catabo lic response in the host. The mechanism by which the metabolic state affect s the resistance to infection apparently involves amino acid metabolism.