KINETICS OF ENDOTOXIN AND TUMOR-NECROSIS-FACTOR APPEARANCE IN PORTAL AND SYSTEMIC CIRCULATION AFTER HEMORRHAGIC-SHOCK IN RATS

Objective This study was performed to investigate gut-derived bacteria l translocation and the time course of endotoxin (lipopolysaccharide [ LPS]) and tumor necrosis factor (TNF) appearance, both in portal and s ystemic circulation. Summary Background Data The significance of intes tinal bacteria/endotoxin translocation or TNF formation in the develop ment of systemic sepsis has been disputed. Methods A rat model of hemo rrhagic shock (30-35 mm Hg for 90 min) and resuscitation was used. Res ults Bacterial translocation was histologically observed in the small intestinal wall 30 minutes after resuscitation. A significant increase in LPS concentrations was found in the portal vein (91.7 +/- 30.6 pg/ mL) at 90 minutes, which remained steady until 150 minutes after shock . Lipopolysaccharide increased in the systemic circulation, the levels became significant at 120 minutes, and peaked (66.5 +/- 39.2 pg/mL) 1 50 minutes after shock. Tumor necrosis factor concentrations were foun d to be significantly elevated in both portal and systemic circulation (75.6 +/- 22.1 vs. 58.4 +/- 14.1 pg/mL) at 90 minutes post-shock. Alt hough there was no further increase in TNF concentration in the portal blood, TNF peaked (83.5 +/- 17.7 pg/mL) in systemic circulation at 12 0 minutes and still was markedly increased at 150 minutes post-shock. In addition, higher LPS and TNF concentrations in systemic circulation were found in the nonsurvivors than in the surviving animals at the e nd of resuscitation. Conclusions These results suggest that hemorrhagi c shock may lead to early bacterial translocation in the intestinal wa ll and transient access of gut-derived LPS and LPS-induced mediators i nto the circulation predominantly via the portal circulation.