Tranexamic Acid Suppresses the Release of Mitochondrial Damps and Reduces Lung Inflammation in a Murine Burn Model

Background Severe burn injuries are known to initiate a profound systemic inflammatory response (SIRS) that may lead to burn shock and other SIRS related complications. Damage associated molecular patterns (DAMPs) are important early signaling molecules that initiate SIRS after burn injury. Previous work in a rodent model has shown that application of a topical immune modulator (p38MAPK inhibitor) applied directly to the burn wound decreases cytokine expression, reduces pulmonary inflammation and edema. Our group has demonstrated that tranexamic acid (TXA) – in addition to its use as an anti-fibrinolytic – has cell protective in vitro effects. We hypothesized that administration of TXA after burn injury would attenuate DAMP release and reduce lung inflammation. Methods C57/BL6 male mice underwent a 40% TBSA scald burn. Sham animals underwent the same procedure in room temperature water. One treatment group received the topical application of p38MAPK inhibitor after burn injury. The other treatment group received an IP administration of TXA after burn injury. Animals were sacrificed at 5 hours. Plasma was collected by cardiac puncture. MtDNA levels in plasma were determined by qPCR. Syndecan-1 levels in plasma were measured by ELISA. Lungs were harvested, fixed and paraffin embedded. Sections of lungs were stained for antigen to detect macrophages. Results Topical p38MAPK inhibitor and TXA significantly attenuated mtDNA release. Both TXA and the topical p38MAPK inhibitor reduced lung inflammation as represented by decreased macrophage infiltration. Syndecan-1 levels showed no difference between burn and treatment groups. Conclusion Both p38 MAPK inhibitor and TXA demonstrated the ability to attenuate burn induced DAMP release and lung inflammation. Beyond its role as an anti-fibrinolytic, TXA may have significant anti-inflammatory effects pertinent to burn resuscitation. Further study is required; however, TXA may be a useful adjunct in burn resuscitation. Correspondence Author: Damien Wilson Carter, MD, FACS, Assistant Professor of Surgery, Tufts University School of Medicine, Maine Medical Center, Department of Surgery, Acute Care Surgery Division, 887 Congress Street, Suite #210, Portland, Maine 04102. Email: dcarter@mmc.org. Office: 207-661-7078, Cell: 206-234-6828 The authors have NO conflicts of interest to declare. Funding: This project was funded by the American Association for the Surgery of Trauma (AAST) Research & Education Scholarship This manuscript has never been previously presented. It is slated for a podium presentation at the 77th Annual Meeting of the American Association for the Surgery of Trauma September 26th - 29th, 2018 in San Diego, California © 2018 Lippincott Williams & Wilkins, Inc.

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