Tranexamic Acid Attenuates the Loss of Lung Barrier Function in a Rat Model of Polytrauma and Hemorrhage with Resuscitation

Xiaowu Wu, Michael A. Dubick, Martin G. Schwacha, Andrew P. Cap, Daniel N. Darlington

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

INTRODUCTION:: Severe trauma, hemorrhage and resuscitation can lead to a trauma related acute lung injury that involves rapid infiltration of immune cells and platelets. This infiltration involves exymatic degradation of matrix proteins, including plasmin, and causes loss of barrier function. Since tranexamic acid (TXA) inhibits plasminogen/ plasmin binding to target substrates, it may attenuate loss of barrier function after severe trauma, hemorrhage and resuscitation. METHODS:: Sprague-Dawley rats were subjected to polytrauma (laparotomy, and trauma to intestines, liver, right leg skeletal muscle and right femur fracture), then bled 40% of their blood volume. One hour after completion of polytrauma and hemorrhage, resuscitation was begun with fresh whole blood (FWB) or FWB with prior bolus administration of TXA (10?mg/kg in 0.2?ml). RESULTS:: Polytrauma, hemorrhage and resuscitation with FWB led to an elevation in lung water content that was significantly reduced with TXA administration. Polytrauma and hemorrhage led to rise in the number of neutrophils/monocytes and platelets in the lungs, and a rise in myeloperoxidase (MPO), neutrophil elastase and complement C5a content. While resuscitation with FWB significantly reduced the cellular infiltrate and MPO, FWB/TXA further reduced the levels of neutrophil/ monocytes, neutrophil elastase, and complement C5a. Polytrauma and hemorrhage led to rise in lung plasmin activity that was significantly reduced with either FWB or FWB/TXA resuscitation. CONCLUSION:: Severe trauma and hemorrhage leads to increases in lung water content, and immune cell, platelets, MPO, elastase and C5a content in lung tissue, all markers of inflammation and acute lung injury. The addition of TXA to FWB resuscitation markedly attenuated the rise in these parameters suggesting its utility in treating acute lung injury.

Original languageEnglish (US)
JournalShock
DOIs
StateAccepted/In press - Sep 19 2016

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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