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Early tranexamic acid administration: A protective effect on gut barrier function following ischemia/reperfusion injury

Diebel, Mark E. MD; Diebel, Lawrence N. MD; Manke, Charles W. PhD; Liberati, David M. MS; Whittaker, John R.

Journal of Trauma and Acute Care Surgery: December 2015 - Volume 79 - Issue 6 - p 1015–1022
doi: 10.1097/TA.0000000000000703
WTA Plenary Papers
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BACKGROUND The mucus barrier is a critical component of the gut barrier and may be disrupted by pancreatic enzymes following trauma/hemorrhagic shock (T/HS). Luminal strategies against pancreatic enzyme activation or contact with the intestine are protective of the mucus layer and gut barrier integrity following T/HS. There is increasing evidence the use of tranexamic acid (TA) attenuates inflammatory responses in cardiac surgery and is readily absorbed from the gut. We therefore postulated that systemic administration of TA would attenuate mucus degradation and gut barrier failure following T/HS. This was studied in an in vitro model.

METHODS Confluent monolayers of HT29-MTX (mucus-producing clone) and Caco-2 cocultures were exposed to 90 minutes of hypoxia followed by reoxygenation (H/R), luminal trypsin (5 μM), or both treatment groups. In a subset of experiments, TA (40 μM or 150 μM) was added to the basal chamber (systemic side) of intestinal cell cultures immediately following the hypoxic period. Mucus barrier function was indexed by rheologic measurement of both mucus thickness and viscosity (G’, dyne/cm2) and oxidant stress. Intestinal cell barrier integrity was indexed by transepithelial electrical resistance, permeability to fluorescein isothiocyanate–dextran, and apoptosis by flow cytometry.

RESULTS Exposure to both trypsin and H/R of Caco-2/HT29-MTX cocultures led to the most severe effect on mucus barrier function. Administration of TA immediately following hypoxia abrogated the effects noted on mucus barrier function. The epithelial barrier was also most severely impacted by both trypsin and H/R. Addition of TA after the hypoxic event was shown to be protective.

CONCLUSION Intestinal mucus physiochemical properties and intestinal barrier function were most severely impacted by exposure to both trypsin (concentration related) and H/R. The “systemic” administration of TA immediately after the hypoxic period was protective and suggests an additional role for early administration of TA in trauma patients in shock.

From the Marian and Michael Ilitch Department of Surgery (M.E.D., L.N.D., D.M.L., J.R.W.), and Department of Chemical Engineering (C.W.M.), Wayne State University, Detroit, Michigan.

Submitted: February 16, 2015, Revised: March 18, 2015, Accepted: March 23, 2015, Published online: August 28, 2015.

This study was presented at the 45th annual meeting of the Western Trauma Association, March 1–6, 2015, in Telluride, Colorado.

Address for reprints: Lawrence N. Diebel, MD, Department of Surgery, 6C-University Health Center, 4201 Saint Antoine, Detroit, MI 48201; email: ldiebel@med.wayne.edu.

© 2015 Lippincott Williams & Wilkins, Inc.