期刊
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
卷 92, 期 5, 页码 812-820出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TA.0000000000003548
关键词
Tranexamic acid; endothelial glycocalyx; microfluidic device
Early administration of TXA protects against degradation of endothelial glycocalyx, reduces increased permeability and the development of a fibrinolytic phenotype. This results in decreased neutrophil adherence and transmigration, leading to reduced vascular leakiness.
BACKGROUND: Improved outcomes with early tranexamic acid (TXA) following trauma hemorrhagic shock (T/HS) may be related to its antifibrinolytic, as well as anti-inflammatory properties. Previous in vitro studies have shown that early TXA administration protects against T/HS endothelial barrier dysfunction and associated glycocalyx degradation. An intact endothelial glycocalyx may protect against subsequent neutrophil mediated tissue injury. We postulated that early TXA administration would mitigate against glycocalyx damage and resultant neutrophil adherence and transmigration through the endothelial barrier. This was studied in vitro using a microfluidic flow platform. METHODS: Human umbilical vein endothelial cell monolayers were subjected to control or shock conditions (hypoxia + epinephrine) followed by administration of TXA 90 minutes or 180 minutes later. RESULTS: Early TXA administration protected against glycocalyx degradation, biomarkers of increased permeability and the development of a fibrinolytic phenotype. This was associated with decreased neutrophil endothelial adherence and transmigration. There were no differences in low versus high TXA concentrations. The protective effects were only significant with early TXA administration. CONCLUSION: There was a concentration and temporal effect of TXA administration on endothelial glycocalyx degradation. This was associated with vascular leakiness as indexed by the relative ratio of Ang-2/1 and polymorphonuclear neutrophil transmigration. Tranexamic acid if administered in patients with T/HS should be administered early; this includes in the prehospital setting. Copyright (c) 2022 American Association for the Surgery of Trauma.
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