Abstract | BACKGROUND: Systemic vascular endothelial injury is a consequence of trauma (T)/ hemorrhagic shock (HS) which results in disturbances of coagulation, inflammation, and endothelial barrier integrity. The effect of T/HS on the endothelium (endotheliopathy of trauma [EoT]) is of intense research interest and may lead to EoT-directed therapies. Administration of tranexamic acid (TXA) in trauma patients is associated with a survival benefit and fewer complications if given early after injury. Mechanisms for this protective effect include the antifibrinolytic and anti-inflammatory effects of TXA. We hypothesized that "early" administration of TXA would abrogate vascular endothelial cell activation and injury after T/HS. This was studied in vitro. METHODS: RESULTS: Endothelial activation and injury as indexed by permeability, ICAM expression, soluble thrombomodulin were increased by H2O2 and/or epinephrine exposure. Biomarkers of endothelial coagulation profile (tPA/PAI-1) demonstrated a profibrinolytic profile (increased tPA and tPA/PAI-1 ratio) after challenge by H2O2 and/or epinephrine. Vascular "leakiness" as indexed by APO-2/APO-1 ratio was also evident. The most profound effects were noted with H2O2/ epinephrine exposure. TXA administration within 60 minutes of H2O2/ epinephrine challenge abolished the adverse effects noted on the endothelial-glycocalyx "double barrier." TXA administration after 60 minutes was not protective. CONCLUSION:
Antifibrinolytic and other protective effects of TXA administration on endothelial injury are time-dependent. This study supports the concept that the clinical efficacy of TXA administration requires "early administration."
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Authors | Lawrence N Diebel, Jonathan V Martin, David M Liberati |
Journal | The journal of trauma and acute care surgery
(J Trauma Acute Care Surg)
Vol. 82
Issue 6
Pg. 1080-1086
(06 2017)
ISSN: 2163-0763 [Electronic] United States |
PMID | 28328682
(Publication Type: Journal Article)
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Chemical References |
- Angiopoietin-1
- Angiopoietin-2
- Antifibrinolytic Agents
- Cell Adhesion Molecules
- Plasminogen Activator Inhibitor 1
- Syndecans
- Thrombomodulin
- Tranexamic Acid
- Hydrogen Peroxide
- Tissue Plasminogen Activator
- Epinephrine
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Topics |
- Angiopoietin-1
(metabolism)
- Angiopoietin-2
(metabolism)
- Antifibrinolytic Agents
(administration & dosage, therapeutic use)
- Cell Adhesion Molecules
(metabolism)
- Endothelium, Vascular
(drug effects, injuries, physiopathology)
- Epinephrine
(pharmacology)
- Human Umbilical Vein Endothelial Cells
(drug effects, physiology)
- Humans
- Hydrogen Peroxide
(pharmacology)
- In Vitro Techniques
- Plasminogen Activator Inhibitor 1
(metabolism)
- Shock, Hemorrhagic
(drug therapy, physiopathology)
- Syndecans
(metabolism)
- Thrombomodulin
(metabolism)
- Tissue Plasminogen Activator
(metabolism)
- Tranexamic Acid
(administration & dosage, therapeutic use)
- Wounds and Injuries
(drug therapy, physiopathology)
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