Research ArticlesSHOCK

Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock

Science Translational Medicine  23 Jan 2013:
Vol. 5, Issue 169, pp. 169ra11
DOI: 10.1126/scitranslmed.3005046

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Stopping Shock

In emergency medicine, shock can be, indeed, shocking. Shock arises from several conditions, including heart attacks, infection, internal bleeding, and trauma, and results in rapid multiorgan failure. Despite its prevalence in the emergency room, the causes of shock are not well understood. DeLano et al. hypothesized that the underlying cause of shock is the leakage of pancreatic enzymes from the lumen into the wall of the intestine, which “self-digest” the intestinal tissue, leading to inflammation and organ damage. To test this hypothesis and ultimately stop shock, the authors treated animal models of experimental shock with various enzyme inhibitors delivered into the lumen of the intestine.

Three rat models of experimental shock were used: hemorrhagic (bleeding), septic (infection), and toxic (endotoxin). Because of its rapid onset and damaging sequelae, suspected shock needs to be treated immediately. One hour after induction of shock, animals were treated with one of three enzymatic inhibitors, including tranexamic acid, which is approved for use in people in the United States. In all treated groups, enzymatic blockade prevented microhemorrhages and increased survival compared with untreated animals. Most (>80%) of untreated animals suffered cardiac and respiratory arrest and died from shock. Moreover, treatment with the enzyme inhibitors prevented loss of villi and destruction of the mucosal layer associated with autodigestion of intestinal wall tissue.

Owing to the prolonged survival in three different rodent models, this enzymatic blockade approach is poised for translation to clinical trials. Notably, a recent case study by these authors showed success of this enzymatic blockade approach in one patient, which gives hope for stopping more cases of shock in humans.