SPLANCHNIC AND SYSTEMIC HEMODYNAMIC-RESPONSES TO PORTAL-VEIN ENDOTOXIN AFTER RESUSCITATION FROM HEMORRHAGIC-SHOCK

Background. Hemorrhagic shock and sepsis are usually studied separatel y or in rodents. This study combined the two insults in a large animal model. Methods. Anesthetized pigs were bled, held in shock for 1 hour , and then resuscitated with fluid. After 3 days, Escherichia coli end otoxin LPS) was infused into the portal vein (150 mu g/kg X 30 min) to mimic the effect of enteric substances breaching the mucosal barrier. Systemic and splanchnic hemodynamics, circulating leukocytes, and pla sma levels of tumor necrosis factor (TNF) were measured in five groups : 40% hemorrhage plus fluid only resuscitation, 40% hemorrhage plus fl uid-blood resuscitation, 50% hemorrhage plus fluid-blood resuscitation , sham, or sham plus 5 mu g/kg LPS priming dose instead of hemorrhage. Results. On day 4 before infusion of LPS, there were no differences b etween groups in hemodynamics or O-2 utilization, but systemic O-2 del ivery and O-2 consumption were each reduced in the hemorrhaged groups because of the hemodilution associated with resuscitation. For 3 hours after infusion of LPS, all animals received aggressive fluid and resp iratory support, but arterial blood pressure decreased, and systemic O -2 utilization, splanchnic O-2 utilization, and arterial lactate level increased; there were no differences between groups. In the 50% group compared with sham, LPS-evoked decreases in cardiac index and stroke index were eliminated, and LPS-evoked tachycardia, pulmonary and syste mic vasoconstriction, and increases in hepatic and portal vein lactate levels were blunted. Despite similar leukocyte counts before infusion of LPS and similar leukopenia after LPS infusion, plasma LPS level wa s higher in the 50% compared with sham. Furthermore, LPS evoked increa ses in portal and hepatic vein plasma TNF in the shams, but those chan ges were reduced in the 50% group. Conclusions. Most responses to LPS were similar after hemorrhagic shock or a sham operation, which is inc onsistent with the concept of ''priming.'' LPS-evoked increases in pla sma TNF were blunted after shock, probably because of trauma-induced i mmune dysfunction. A combined shock plus septic challenge in a large a nimal model may be valuable for investigating the pathogenic mechanism in human beings.