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      Resuscitating the Endothelial Glycocalyx in Trauma and Hemorrhagic Shock

      review-article
      , MD, MPH, MT(ASCP), FACS * , , , BS , , BS , , MD, MS, FACS * , , MD, FACS *
      Annals of Surgery Open
      Wolters Kluwer Health, Inc.
      endothelial glycocalyx, hemorrhagic shock, resuscitation

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          Abstract

          The endothelium is lined by a protective mesh of proteins and carbohydrates called the endothelial glycocalyx (EG). This layer creates a negatively charged gel-like barrier between the vascular environment and the surface of the endothelial cell. When intact the EG serves multiple functions, including mechanotransduction, cell signaling, regulation of permeability and fluid exchange across the microvasculature, and management of cell-cell interactions. In trauma and/or hemorrhagic shock, the glycocalyx is broken down, resulting in the shedding of its individual components. The shedding of the EG is associated with increased systemic inflammation, microvascular permeability, and flow-induced vasodilation, leading to further physiologic derangements. Animal and human studies have shown that the greater the severity of the injury, the greater the degree of shedding, which is associated with poor patient outcomes. Additional studies have shown that prioritizing certain resuscitation fluids, such as plasma, cryoprecipitate, and whole blood over crystalloid shows improved outcomes in hemorrhaging patients, potentially through a decrease in EG shedding impacting downstream signaling. The purpose of the following paragraphs is to briefly describe the EG, review the impact of EG shedding and hemorrhagic shock, and begin entertaining the notion of directed resuscitation. Directed resuscitation emphasizes transitioning from macroscopic 1:1 resuscitation to efforts that focus on minimizing EG shedding and maximizing its reconstitution.

          Abstract

          Mini Abstract

          This review is aimed to seek to give the reader a brief introduction regarding the structure and function of the endothelial glycocalyx, review and summarize significant findings noted in hemorrhagic shock, and suggest future directions for research and exploration.

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          The endothelial glycocalyx: composition, functions, and visualization

          This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging.
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            Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock

            After a person has been injured, prehospital administration of plasma in addition to the initiation of standard resuscitation procedures in the prehospital environment may reduce the risk of downstream complications from hemorrhage and shock. Data from large clinical trials are lacking to show either the efficacy or the risks associated with plasma transfusion in the prehospital setting.
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              A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients.

              To investigate the association between markers of acute endothelial glycocalyx degradation, inflammation, coagulopathy, and mortality after trauma. Hyperinflammation and acute coagulopathy of trauma predict increased mortality. High catecholamine levels can directly damage the endothelium and may be associated with enhanced endothelial glycocalyx degradation, evidenced by high circulating syndecan-1. Prospective cohort study of trauma patients admitted to a Level 1 Trauma Centre in 2003 to 2005. Seventy-five patients were selected blindly post hoc from 3 predefined injury severity score (ISS) groups ( 27). In all patients, we measured 17 markers of glycocalyx degradation, inflammation, tissue and endothelial damage, natural anticoagulation, and fibrinolysis (syndecan-1, IL-6, IL-10, histone-complexed DNA fragments, high-mobility group box 1 (HMGB1), thrombomodulin, von Willebrand factor, intercellular adhesion molecule-1, E-selectin, protein C, tissue factor pathway inhibitor (TFPI), antithrombin, D-dimer, tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), soluble uPA receptor, and plasminogen activator inhibitor-1), hematology, coagulation, catecholamines, and assessed 30-day mortality. Variables were compared in patients stratified according to syndecan-1 median. Patients with high circulating syndecan-1 had higher catecholamines, IL-6, IL-10, histone-complexed DNA fragments, HMGB1, thrombomodulin, D-dimer, tPA, uPA (all P < 0.05), and 3-fold increased mortality (42% vs. 14%, P = 0.006) despite comparable ISS (P = 0.351). Only in patients with high glycocalyx degradation was higher ISS correlated with higher adrenaline, IL-6, histone-complexed DNA fragments, HMGB1, thrombomodulin, and APTT, lower protein C (all P < 0.05), unchanged TFPI and blunted D-dimer response (P < 0.001) because D-dimer was profoundly increased even at low ISS. After adjusting for age and ISS, syndecan-1 was an independent predictor of mortality (OR: 1.01 [95%CI, 1.00-1.02]; P = 0.043). In trauma patients, high circulating syndecan-1, a marker of endothelial glycocalyx degradation, is associated with inflammation, coagulopathy and increased mortality.
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                Author and article information

                Journal
                Ann Surg Open
                Ann Surg Open
                AS9
                Annals of Surgery Open
                Wolters Kluwer Health, Inc. (Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103 )
                2691-3593
                September 2023
                28 June 2023
                : 4
                : 3
                : e298
                Affiliations
                From the [* ]Department of Surgery, Division of Trauma, Critical Care, Burns, and Emergency Surgery, The University of Arizona, Tucson, AZ
                []Department of Surgery, University of Arizona College of Medicine, Tucson, AZ.
                Author notes
                Reprints: Tanya Anand, MD, MPH, MT(ASCP), FACS, University of Arizona Department of Surgery, Division of Trauma, Critical Care, Burn & Emergency Surgery, 1501 N. Campbell Ave, PO Box 245063, Rm 5411, Tucson, AZ 85724. E-mail: tanyaanand@ 123456arizona.edu .
                Article
                00002
                10.1097/AS9.0000000000000298
                10513357
                37746602
                e3e9dd04-8e1b-4e92-843b-474c93b9fd87
                Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 23 November 2022
                : 20 May 2023
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                Review Paper
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                endothelial glycocalyx,hemorrhagic shock,resuscitation

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