Events leading to intestinal barrier failure and systemic inflammation following hemorrhagic shock

Abstract

Hemorrhagic shock (HS) leads to systemic inflammatory response syndrome (SIRS), a potential deleterious complication. A current hypothesis states that gut barrier loss is crucial in the development of SIRS. We aimed at elucidating the sequence of events leading to gut barrier loss and SIRS following HS.Rats were subjected to HS and sacrificed at 15, 30, 60, 90 min after HS, and compared with sham controls. Intestinal neutrophil influx (NI), tight junction (TJ) integrity, enterocyte integrity, bacterial translocation (BT), and SIRS were assessed.HS leads to early NI from 15 min after HS, followed by a significant loss of TJ proteins Claudin‐3 and ZO‐1 from 30 and 60 min after HS, respectively (100% versus 71% and 100% versus 41%, respectively, P<0.05, students t‐test (stt)). Enterocyte integrity loss measured by plasma Ileal Lipid Binding Protein levels, is markedly increased from 60 min after HS (0.6 versus 11.8 ng/ml, P<0.0001, stt). Intestinal barrier function loss detectable from 60 min after HS is represented by BT (0.0 versus 47.9 CFU/g tissue, p<0.005, wilcoxon signed rank test (wsrt)). SIRS measured by plasma TNFα levels is significantly elevated from 60 min after HS (0.0 versus 26.1 pg/ml, p<0.05, wsrt).HS leads to NI and gut barrier integrity loss, followed by BT and SIRS within 90 min after shock. Ongoing studies are directed at unraveling the causal relation between succeeding events.