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 injury.


METHODS
A prospective, controlled animal study.


METHODS
Animal laboratory.


METHODS
Young male Wistar rats.


METHODS
Antibiotic decontamination of rats was performed 4 days before intragastric inoculation with a selected Escherichia coli strain (10(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.


RESULTS
During 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 micromol 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).


CONCLUSIONS
Gut 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.
Schlegel
L
L
INSERM U402, Hôpital Saint-Antoine, Assistance Publique, Hôpitaux de Paris, France.
Coudray-Lucas
C
C
Barbut
F
F
Le Boucher
J
J
Pernet
P
P
Cynober
L
L
D000818:Animals; D018988:Bacterial Translocation / Q000502:physiology*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D004927:Escherichia coli Infections / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D008099:Liver / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000382:microbiology; D008297:Male; D008643:Mesentery / Q000382:microbiology; D009584:Nitrogen / Q000652:urine; D009929:Organ Size; D011446:Prospective Studies; D011506:Proteins / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D013950:Thymus Gland / Q000382:microbiology / Q000473:pathology; D013997:Time Factors
D011506:Proteins; D009584:Nitrogen