GUT-DERIVED MESENTERIC LYMPH BUT NOT PORTAL BLOOD INCREASES ENDOTHELIAL-CELL PERMEABILITY AND PROMOTES LUNG INJURY AFTER HEMORRHAGIC-SHOCK

Objective To determine whether gut-derived factors leading to organ in jury and increased endothelial cell permeability would be present in t he mesenteric lymph at higher levels than in the portal blood of rats subjected to hemorrhagic shock. This hypothesis was tested by examinin g the effect of portal blood plasma and mesenteric lymph on endothelia l cell monolayers and the interruption of mesenteric lymph flow on sho ck-induced lung injury. Summary Background Data The absence of detecta ble bacteremia or endotoxemia in the portal blood of trauma victims ca sts doubt on the role of the gut in the generation of multiple organ f ailure. Nevertheless, previous experimental work has clearly documente d the connection between shock and gut injury as well as the concept o f gut-induced sepsis and distant organ failure. One explanation for th is apparent paradox would be that gut-derived inflammatory factors are reaching the lung and systemic circulation via the gut lymphatics rat her than the portal circulation. Methods Human umbilical vein endothel ial cell monolayers, grown in two-compartment systems, were exposed to media, shamshock, or postshock portal blood plasma or lymph, and perm eability to rhodamine (10K) was measured. Sprague-Dawley rats were sub jected to 90 minutes of sham or actual shock and shock plus lymphatic division (before and after shock). Lung permeability, pulmonary myelop eroxidase levels, alveolar apoptosis, and bronchoalveolar fluid protei n content were used to quantitate lung injury. Results Postshock lymph increased endothelial cell monolayer permeability but not postshock p lasma, sham-shock lymph/plasma, or medium. Lymphatic division before h emorrhagic shock prevented shock-induced increases in lung permeabilit y to Evans blue dye and alveolar apoptosis and reduced pulmonary MPO l evels. In contrast, division of the mesenteric lymphatics at the end o f the shock period but before reperfusion ameliorated but failed to pr event increased lung permeability; alveolar apoptosis, and MPO accumul ation. Conclusions Gut barrier failure after hemorrhagic shock may be involved in the pathogenesis of shock-induced distant organ injury via gut-derived factors carried in the mesenteric lymph rather than the p ortal circulation.