Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock

Jordan E. Fishman, Sharvil U. Sheth, Gal Levy, Vamsi Alli, Qu Lu, Dazhong Xu, Yung Qin, Xiaofa Qin, Edwin A. Deitch

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Objective: To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in the pathogenesis of trauma shock-induced gut and lung injury. Background: Gut origin sepsis studies have highlighted the importance of the systemic component (ischemia-reperfusion) of gut injury, whereas the intraluminal component is less well studied. Methods: In rats subjected to trauma hemorrhagic shock (T/HS) or sham shock, the role of pancreatic enzymes in gut injury was tested by diversion of pancreatic enzymes via pancreatic duct exteriorization whereas the role of the mucus layer was tested via the enteral administration of a mucus surrogate. In addition, the role of mast cells was assessed by measuring mast cell activation and the ability of pharmacologic inhibition of mast cells to abrogate gut and lung injury. Gut and mucus injury was characterized functionally, morphologically, and chemically. Results: Pancreatic duct exteriorization abrogated T/HS-induced gut barrier loss and limited chemical mucus changes. The mucus surrogate prevented T/HS-induced gut and lung injury. Finally, pancreatic enzyme-induced gut and lung injury seems to involve mast cell activation because T/HS activates mast cells and pharmacologic inhibition of intestinal mast cells prevented T/HS-induced gut and lung injury. Conclusions: These results indicate that gut and gut-induced lung injury after T/HS involves a complex process consisting of intraluminal digestive enzymes, the unstirred mucus layer, and a systemic ischemic-reperfusion injury. This suggests the possibility of intraluminal therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)1112-1120
Number of pages9
JournalAnnals of surgery
Volume260
Issue number6
DOIs
StatePublished - 2014

Keywords

  • Hemorrhagic shock
  • Intestinal mast cells
  • Intestinal mucus
  • Ischemic-reperfusion injury
  • Shock
  • Trauma

ASJC Scopus subject areas

  • Surgery

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    Fishman, J. E., Sheth, S. U., Levy, G., Alli, V., Lu, Q., Xu, D., Qin, Y., Qin, X., & Deitch, E. A. (2014). Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock. Annals of surgery, 260(6), 1112-1120. https://doi.org/10.1097/SLA.0000000000000631