Effects of a single aerobic exercise on perfused boundary region and microvascular perfusion: a field study.

The endothelium and the glycocalyx play a pivotal role in regulating microvascular function and perfusion in health and critical illness. It is unknown today, whether aerobic exercise immediately affects dimensions of the endothelial surface layer (ESL) in relation to microvascular perfusion as a physiologic adaption to increased nutritional demands. This monocentric observational study was designed to determine real-time ESL and perfusion measurements of the sublingual microcirculation using sidestream dark field imaging performed in 14 healthy subjects before and after completing a 10 km trial running distance. A novel image acquisition and analysis software automatically analysed the perfused boundary region (PBR), an inverse parameter for red blood cell (RBC) penetration of the ESL, in vessels between 5 and 25 µm diameter. Microvascular perfusion was assessed by calculating RBC filling percentage. There was no significant immediate effect of exercise on PBR and RBC filling percentage. Linear regression analysis revealed a distinct association between change of PBR and change of RBC filling percentage (regression coefficient ß: - 0.026; 95% confidence interval - 0.043 to - 0.009; p = 0.006). A single aerobic exercise did not induce a change of PBR or RBC filling percentage. The endothelium of the microvasculature facilitates efficient perfusion in vessels reacting with an increased endothelial surface layer.

Clinical impact of tissue sodium storage.

In recent times, the traditional nephrocentric, two-compartment model of body sodium has been challenged by long-term sodium balance studies and experimental work on the dermal interstitium and endothelial surface layer. In the new paradigm, sodium can be stored without commensurate water retention in the interstitium and endothelial surface layer, forming a dynamic third compartment for sodium. This has important implications for sodium homeostasis, osmoregulation and the hemodynamic response to salt intake. Sodium storage in the skin and endothelial surface layer may function as a buffer during periods of dietary depletion and excess, representing an extra-renal mechanism regulating body sodium and water. Interstitial sodium storage may also serve as a biomarker for sodium sensitivity and cardiovascular risk, as well as a target for hypertension treatment. Furthermore, sodium storage may explain the limitations of traditional techniques used to quantify sodium intake and determine infusion strategies for dysnatraemias. This review is aimed at outlining these new insights into sodium homeostasis, exploring their implications for clinical practice and potential areas for further research for paediatric and adult populations.

Effects of anaesthesia-induced hypotension and phenylephrine on plasma volume expansion by hydroxyethyl starch: A randomised controlled study.

BACKGROUND: Changes in blood haemoglobin concentration indicate plasma volume expansion following hydroxyethyl starch (HES) infusion, but may be affected by vascular tone and HES-induced shedding of the endothelial surface layer (ESL). We hypothesised that anaesthesia-induced hypotension enhances changes in plasma volume as assessed by blood haemoglobin concentration (ΔPVHb , %) following HES infusion. METHODS: Fifty-two patients undergoing abdominal surgery were randomised to receive a continuous infusion of saline (S group) or phenylephrine to restore vascular tone (P group) (n = 26 each). Both groups received an infusion of 8 mL/kg 6% HES solution after induction of general anaesthesia. We compared ΔPVHb at the end of fluid infusion (15 minutes) and 15 minutes later (30 minutes) between the two groups. We assessed changes in ESL structure by measuring plasma concentrations of hyaluronate and syndecan-1. P < .05 was considered statistically significant. RESULTS: Mean arterial blood pressure was lower in the S group approximately by 30-40% compared to the P group (P < .001). ΔPVHb was larger in the S group compared to the P group at 15 minutes (24.9 [5.2] % vs 19.0 [5.2] %; P < .001) and 30 minutes (26.5 [5.9] % vs 16.9 [6.6] %; P < .001). There were no clinically significant differences in plasma concentrations of hyaluronate and syndecan-1 with time and between the groups. CONCLUSIONS: Increased volume expansion of circulating plasma following HES infusion in anaesthesia-induced hypotension compared to when blood pressure is restored by phenylephrine may result from an attenuation of transcapillary fluid filtration, rather than ESL shedding. UMIN Clinical Trial Registration Number: UMIN000017394 (http://www.umin.ac.jp/ctr/index.htm).

Preventive effect on endothelial surface layer damage of Fusu agent in LPS-induced acute lung injury in rats.

Acute lung injury (ALI) is one of major causes of morbidity and mortality in intensive care. In pathophysiological events of ALI, endothelial surface layer (ESL) injury can result in capillary leakage as the initial event. The "Fusu agent", a traditional Chinese medicine, can inhibit inflammatory factors, attenuate lung capillary leak as seen in our previous study. This study was aimed to explore the molecular mechanism of Fusu agent treatment with ALI. Consistent with previous studies, we found that Fusu agent has the protective effect on LPS-induced ALI model rats. Further investigation demonstrated that heparanase activation is necessary for the LPS-induced ALI model to aggravate ESL loss. Fusu agent can inhibit heparanase activation and heparan sulfate proteoglycans' (HSPGs) degradation to mitigate the ESL injury. Furthermore, TNF-α and intercellular adhesion molecule-1 (ICAM-1) were significantly reduced upon Fusu agent pre-treatment to inhibit inflammatory cell influx and neutrophil adhesion in ALI. These findings shed light on the pharmacologic basis for the clinical application of traditional Chinese medicine in treating ALI.

The Pulmonary Endothelial Glycocalyx in ARDS: A Critical Role for Heparan Sulfate.

The endothelial glycocalyx is a glycosaminoglycan-enriched endovascular layer that, with the development of novel fixation and in vivo microscopy techniques, has been increasingly recognized as a major contributor to vascular homeostasis. Sepsis-associated degradation of the endothelial glycocalyx mediates the onset of the alveolar microvascular dysfunction characteristic of sepsis-induced lung injury (such as the Acute Respiratory Distress Syndrome, ARDS). Emerging evidence indicates that processes of glycocalyx reconstitution are necessary for endothelial repair and, as such, are promising therapeutic targets to accelerate lung injury recovery. This review discusses what has been learned about the homeostatic and pathophysiologic role of the pulmonary endothelial glycocalyx during lung health and injury, with the goal to identify promising new areas for future mechanistic investigation.

Coronary microcirculatory pathophysiology: can we afford it to remain a black box?

Coronary microvascular networks play the key role in determining blood flow distribution in the heart. Matching local blood supply to tissue metabolic demand entails continuous adaptation of coronary vessels via regulation of smooth muscle tone and structural dilated vessel diameter. The importance of coronary microcirculation for relevant pathological conditions including angina in patients with normal or near-normal coronary angiograms [microvascular angina (MVA)] and heart failure with preserved ejection fraction (HFpEF) is increasingly recognized. For MVA, clinical studies have shown a prevalence of up to 40% in patients with suspected coronary artery disease and a relevant impact on adverse cardiovascular events including cardiac death, stroke, and heart failure. Despite a continuously increasing number of corresponding clinical studies, the knowledge on pathophysiological cause-effect relations involving coronary microcirculation is, however, still very limited. A number of pathophysiological hypotheses for MVA and HFpEF have been suggested but are not established to a degree, which would allow definition of nosological entities, stratification of affected patients, or development of effective therapeutic strategies. This may be related to a steep decline in experimental (animal) pathophysiological studies in this area during the last 15 years. Since technology to experimentally investigate microvascular pathophysiology in the beating heart is increasingly, in principle, available, a concerted effort to build 'coronary microcirculatory observatories' to close this gap and to accelerate clinical progress in this area is suggested.

A microscopic view on the renal endothelial glycocalyx.

Endothelial cells perform key homeostatic functions such as regulating blood flow, permeability, and aiding immune surveillance for pathogens. While endothelial activation serves normal physiological adaptation, maladaptation of these endothelial functions has been identified as an important effector mechanism in the progression of renal disease as well as the associated development of cardiovascular disease. The primary interface between blood and the endothelium is the glycocalyx. This carbohydrate-rich gel-like structure with its associated proteins mediates most of the regulatory functions of the endothelium. Because the endothelial glycocalyx is a highly dynamic and fragile structure ex vivo, and traditional tissue processing for staining and perfusion-fixation usually results in a partial or complete loss of the glycocalyx, studying its dimensions and function has proven to be challenging. In this review, we will outline the core functions of the glycocalyx and focus on different techniques to study structure-function relationships in kidney and vasculature.

Glomerular endothelial cell injury and cross talk in diabetic kidney disease.

Diabetic kidney disease (DKD) remains a leading cause of new-onset end-stage renal disease (ESRD), and yet, at present, the treatment is still very limited. A better understanding of the pathogenesis of DKD is therefore necessary to develop more effective therapies. Increasing evidence suggests that glomerular endothelial cell (GEC) injury plays a major role in the development and progression of DKD. Alteration of the glomerular endothelial cell surface layer, including its major component, glycocalyx, is a leading cause of microalbuminuria observed in early DKD. Many studies suggest a presence of cross talk between glomerular cells, such as between GEC and mesangial cells or GEC and podocytes. PDGFB/PDGFRß is a major mediator for GEC and mesangial cell cross talk, while vascular endothelial growth factor (VEGF), angiopoietins, and endothelin-1 are the major mediators for GEC and podocyte communication. In DKD, GEC injury may lead to podocyte damage, while podocyte loss further exacerbates GEC injury, forming a vicious cycle. Therefore, GEC injury may predispose to albuminuria in diabetes either directly or indirectly by communication with neighboring podocytes and mesangial cells via secreted mediators. Identification of novel mediators of glomerular cell cross talk, such as microRNAs, will lead to a better understanding of the pathogenesis of DKD. Targeting these mediators may be a novel approach to develop more effective therapy for DKD.

Microvascular Endothelial Glycocalyx Surface Layer Visualization and Quantification.

As a primary interface between the blood and underlying vascular wall, the endothelial glycocalyx layer is common to all blood vessels and covers the luminal surface of all endothelial cells. The endothelial glycocalyx has important roles as a regulator of microvascular endothelial functions such as mechanotransduction, leukocyte adhesion, and microvascular permeability. Disruption of the molecular structure of the endothelial glycocalyx disturbs physiological, and hemodynamic processes associated with the microvascular wall leads to microvascular hyperpermeability. Studying the glycocalyx is challenging because cultured cells present aberrant glycocalyx structure and tissue fixation techniques lead to the degradation and loss of this fine and delicate layer. Therefore, studying the glycocalyx requires in vivo imaging of the microcirculation. Here we describe two techniques for direct imaging and assessment of the glycocalyx surface layer integrity using intravital microscopy (IVM), a method widely used in the study of the dynamic changes that occur in the microcirculation during inflammation or injury.

The effect of the endothelial surface layer on cell-cell interactions in microvessel bifurcations.

Red blood cells (RBCs) carry oxygen and make up 40-45% of blood by volume in large vessels down to 10% or less in smaller capillaries. Because of their finite size and large volume fraction, they are heterogeneously distributed throughout the body. This is partially because RBCs are distributed or partitioned nonuniformly at diverging vessel bifurcations where blood flows from one vessel into two. Despite its increased recognition as an important player in the microvasculature, few studies have explored how the endothelial surface layer (ESL; a vessel wall coating) may affect partitioning and RBC dynamics at diverging vessel bifurcations. Here, we use a mathematical and computational model to consider how altering ESL properties, as can occur in pathological scenarios, change RBC partitioning, deformation, and penetration of the ESL. The two-dimensional finite element model considers pairs of cells, represented by interconnected viscoelastic elements, passing through an ESL-lined diverging vessel bifurcation. The properties of the ESL include the hydraulic resistivity and an osmotic pressure difference modeling how easily fluid flows through the ESL and how easily the ESL is structurally compressed, respectively. We find that cell-cell interaction leads to more uniform partitioning and greatly enhances the effects of ESL properties, especially for deformation and penetration. This includes the trend that increased hydraulic resistivity leads to more uniform partitioning, increased deformation, and decreased penetration. It also includes the trend that decreased osmotic pressure increases penetration.

Nafion: New and Old Insights into Structure and Function.

The work reports a number of results on the dynamics of swelling and inferred nanostructure of the ion-exchange polymer membrane Nafion in different aqueous solutions. The techniques used were photoluminescent and Fourier transform IR (FTIR) spectroscopy. The centers of photoluminescence were identified as the sulfonic groups localized at the ends of the perfluorovinyl ether (Teflon) groups that form the backbone of Nafion. Changes in deuterium content of water induced unexpected results revealed in the process of polymer swelling. In these experiments, deionized (DI) water (deuterium content 157 ppm) and deuterium depleted water (DDW) with deuterium content 3 PPM, were investigated. The strong hydration of sulfonic groups involves a competition between ortho- and para-magnetic forms of a water molecule. Deuterium, as it seems, adsorbs competitively on the sulfonic groups and thus can change the geometry of the sulfate bonds. With photoluminescent spectroscopy experiments, this is reflected in the unwinding of the polymer fibers into the bulk of the adjoining water on swelling. The unwound fibers do not tear off from the polymer substrate. They form a vastly extended "brush" type structure normal to the membrane surface. This may have implications for specificity of ion transport in biology, where the ubiquitous glycocalyx of cells and tissues invariably involves highly sulfated polymers such asheparan and chondroitin sulfate.

Modeling of the cerebral blood circulation in a capillary network accounting for the influence of the endothelial surface layer.

BACKGROUND AND OBJECTIVE: The paper describes a mathematical model of blood flow in capillaries with accounting for the endothelial surface layer (ESL). METHOD: The influence of ESL is modeled by a boundary layer with zero flow velocity. Finite element modeling and an analytical approach based on the homogenization of the core region of blood flow occupied by erythrocytes are developed to describe the resistance of a capillary. The reliability of the results obtained is verified for different values of the discharge hematocrit and vessel diameter using known in vivo data. RESULTS: The proposed approach is applied to the numerical simulation of blood circulation in a capillary network of the germinal matrix of infants born at 25 gestational weeks. The influence of the hematocrit level and effective thickness of ESL on the resistance of the capillary network of the germinal matrix of preterm infants is studied. It was found that a decrease in the effective thickness of ESL in the capillary network (and/or a decrease in the hematocrit) leads to reducing the resistance of the capillary network. CONCLUSION: A decrease in the effective thickness of ESL in the capillary network leads to an increase in the pressure drop in arterioles, which may be considered as an additional risk factor for hemorrhages in fragile blood vessels within the germinal matrix.

Dependence of red blood cell dynamics in microvessel bifurcations on the endothelial surface layer's resistance to flow and compression.

Red blood cells (RBCs) make up 40-45% of blood and play an important role in oxygen transport. That transport depends on the RBC distribution throughout the body, which is highly heterogeneous. That distribution, in turn, depends on how RBCs are distributed or partitioned at diverging vessel bifurcations where blood flows from one vessel into two. Several studies have used mathematical modeling to consider RBC partitioning at such bifurcations in order to produce useful insights. These studies, however, assume that the vessel wall is a flat impenetrable homogeneous surface. While this is a good first approximation, especially for larger vessels, the vessel wall is typically coated by a flexible, porous endothelial glycocalyx or endothelial surface layer (ESL) that is on the order of 0.5-1 µm thick. To better understand the possible effects of this layer on RBC partitioning, a diverging capillary bifurcation is analyzed using a flexible, two-dimensional model. In addition, the model is also used to investigate RBC deformation and RBC penetration of the ESL region when ESL properties are varied. The RBC is represented using interconnected viscoelastic elements. Stokes flow equations (viscous flow) model the surrounding fluid. The flow in the ESL is modeled using the Brinkman approximation for porous media with a corresponding hydraulic resistivity. The ESL's resistance to compression is modeled using an osmotic pressure difference. One cell passes through the bifurcation at a time, so there are no cell-cell interactions. A range of physiologically relevant hydraulic resistivities and osmotic pressure differences are explored. Decreasing hydraulic resistivity and/or decreasing osmotic pressure differences (ESL resistance to compression) produced four behaviors: (1) RBC partitioning nonuniformity increased slightly; (2) RBC deformation decreased; (3) RBC velocity decreased relative to blood flow velocity; and (4) RBCs penetrated more deeply into the ESL. Decreasing the ESL's resistance to flow and/or compression to pathological levels could lead to more frequent cell adhesion and clotting as well as impaired vascular regulation due to weaker ATP and nitric oxide release. Potential mechanisms that can contribute to these behaviors are also discussed.

Studying the Endothelial Glycocalyx in vitro: What Is Missing?

All human cells are coated by a surface layer of proteoglycans, glycosaminoglycans (GAGs) and plasma proteins, called the glycocalyx. The glycocalyx transmits shear stress to the cytoskeleton of endothelial cells, maintains a selective permeability barrier, and modulates adhesion of blood leukocytes and platelets. Major components of the glycocalyx, including syndecans, heparan sulfate, and hyaluronan, are shed from the endothelial surface layer during conditions including ischaemia and hypoxia, sepsis, atherosclerosis, diabetes, renal disease, and some viral infections. Studying mechanisms of glycocalyx damage in vivo can be challenging due to the complexity of immuno-inflammatory responses which are inextricably involved. Previously, both static as well as perfused in vitro models have studied the glycocalyx, and have reported either imaging data, assessment of barrier function, or interactions of blood components with the endothelial monolayer. To date, no model has simultaneously incorporated all these features at once, however such a model would arguably enhance the study of vasculopathic processes. This review compiles a series of current in vitro models described in the literature that have targeted the glycocalyx layer, their limitations, and potential opportunities for further developments in this field.

The Effects of Resuscitative Fluid Therapy on the Endothelial Surface Layer.

The goal of resuscitative fluid therapy is to rapidly expand circulating blood volume in order to restore tissue perfusion. Although this therapy often serves to improve macrohemodynamic parameters, it can be associated with adverse effects on the microcirculation and endothelium. The endothelial surface layer (ESL) provides a protective barrier over the endothelium and is important for regulating transvascular fluid movement, vasomotor tone, coagulation, and inflammation. Shedding or thinning of the ESL can promote interstitial edema and inflammation and may cause microcirculatory dysfunction. The pathophysiologic perturbations of critical illness and rapid, large-volume fluid therapy both cause shedding or thinning of the ESL. Research suggests that restricting the volume of crystalloid, or "clear" fluid, may preserve some ESL integrity and improve outcome based on animal experimental models and preliminary clinical trials in people. This narrative review critically evaluates the evidence for the detrimental effects of resuscitative fluid therapy on the ESL and provides suggestions for future research directions in this field.

The Glomerular Endothelium Restricts Albumin Filtration.

Inflammatory activation and/or dysfunction of the glomerular endothelium triggers proteinuria in many systemic and localized vascular disorders. Among them are the thrombotic microangiopathies, many forms of glomerulonephritis, and acute inflammatory episodes like sepsis and COVID-19 illness. Another example is the chronic endothelial dysfunction that develops in cardiovascular disease and in metabolic disorders like diabetes. While the glomerular endothelium is a porous sieve that filters prodigious amounts of water and small solutes, it also bars the bulk of albumin and large plasma proteins from passing into the glomerular filtrate. This endothelial barrier function is ascribed predominantly to the endothelial glycocalyx with its endothelial surface layer, that together form a relatively thick, mucinous coat composed of glycosaminoglycans, proteoglycans, glycolipids, sialomucins and other glycoproteins, as well as secreted and circulating proteins. The glycocalyx/endothelial surface layer not only covers the glomerular endothelium; it extends into the endothelial fenestrae. Some glycocalyx components span or are attached to the apical endothelial cell plasma membrane and form the formal glycocalyx. Other components, including small proteoglycans and circulating proteins like albumin and orosomucoid, form the endothelial surface layer and are bound to the glycocalyx due to weak intermolecular interactions. Indeed, bound plasma albumin is a major constituent of the endothelial surface layer and contributes to its barrier function. A role for glomerular endothelial cells in the barrier of the glomerular capillary wall to protein filtration has been demonstrated by many elegant studies. However, it can only be fully understood in the context of other components, including the glomerular basement membrane, the podocytes and reabsorption of proteins by tubule epithelial cells. Discovery of the precise mechanisms that lead to glycocalyx/endothelial surface layer disruption within glomerular capillaries will hopefully lead to pharmacological interventions that specifically target this important structure.

Derangement of the endothelial glycocalyx in sepsis.

The vascular endothelial surface is coated by the glycocalyx, a ubiquitous gel-like layer composed of a membrane-binding domain that contains proteoglycans, glycosaminoglycan side-chains, and plasma proteins such as albumin and antithrombin. The endothelial glycocalyx plays a critical role in maintaining vascular homeostasis. However, this component is highly vulnerable to damage and is also difficult to examine. Recent advances in analytical techniques have enabled biochemical, visual and computational investigation of this vascular component. The glycocalyx modulates leukocyte-endothelial interactions, thrombus formation and other processes that lead to microcirculatory dysfunction and critical organ injury in sepsis. It also acts as a regulator of vascular permeability and contains mechanosensors as well as receptors for growth factors and anticoagulants. During the initial onset of sepsis, the glycocalyx is damaged and circulating levels of glycocalyx components, including syndecans, heparan sulfate and hyaluronic acid, can be measured and are reportedly useful as biomarkers for sepsis. Also, a new methodology using side-stream dark-field imaging is now clinically available for assessing the glycocalyx. Multiple factors including hypervolemia and hyperglycemia are toxic to the glycocalyx, and several agents have been proposed as therapeutic modalities, although no single treatment has been proven to be clinically effective. In this article, we review the derangement of the glycocalyx in sepsis. Despite the accumulated knowledge regarding the important roles of the glycocalyx, the relationship between derangement of the endothelial glycocalyx and severity of sepsis or disseminated intravascular coagulation has not been adequately elucidated and further work is needed.

The endothelial glycocalyx: Barrier functions versus red cell hemodynamics: A model of steady state ultrafiltration through a bi-layer formed by a porous outer layer and more selective membrane-associated inner layer.

BACKGROUND: Ultrastructural investigations of the endothelial glycocalyx reveal a layer adjacent to the cell surface with a structure consistent with the primary  ultrafilter of vascular walls. Theory predicts this layer can be no greater than 200-300 nm thick, a result  to be reconciled with observations that red cells and large macromolecules are excluded  from a region 1 micrometer or more from the cell membrane. OBJECTIVE: To determine whether this apparent inconsistency might be accounted for by a model of steady state water and protein transport through a glycocalyx bi-layer formed by a porous outer layer in series with a more selective inner layer. METHODS: Expressions for coupled water and albumin fluxes through the two layers were used to describe steady state ultra-filtration though the bi-layer model. RESULTS: Albumin accumulates at the interface between the porous layer and the selective inner layer. The osmotic pressure of accumulated albumin significantly modifies the observed permeability properties of the microvessel wall by an effective unstirred layer effect. CONCLUSIONS: The model places significant constraints on the outer layer permeability properties . The only outer layer properties that are consistent with measured steady state filtration rates and models of red cell flux through microvessels are an albumin permeability coefficient and hydraulic conductivity more than an order of magnitude larger than the those of the inner layer.

Contrasting effects of albumin and hydroxyethyl starch solutions on physical properties of sodium hyaluronate solution.

Hydroxyethyl starch (HES) solution reportedly sheds the endothelial surface layer (ESL) consisting of polysaccharide glycosaminoglycans, whereas albumin stabilizes the ESL. Here we compared the effects of albumin and HES (MW 130,000) solutions on the physical properties of sodium hyaluronate (NaHA, MW 1.3 × 106) solution, a constituent of the ESL. Partial specific volumes (v) and intrinsic viscosities ([η]) of NaHA in 0.15 M NaCl solution containing albumin or HES (1-3%) were calculated from densities and viscosities extrapolated at infinite dilutions. Flow activation energy (E) of 0.2% NaHA in phosphate-buffered saline containing albumin or HES was obtained from the temperature-dependence of viscosities. A 3% albumin solution decreased v of NaHA by 3% compared to HES. A 3% HES solution, but not albumin, decreased [η] of NaHA by 34%, and decreased E values by 11% compared to albumin. These findings suggest that HES locally restricts NaHA dispersion, whereas albumin contracts NaHA structure.

Shedding of the endothelial glycocalyx is quantitatively proportional to burn injury severity.

Limited information exists regarding endothelial dysfunction following burn injury. This project aims to evaluate whether thermal injury results in shedding of the endothelial glycocalyx in a manner quantitatively proportional to injury severity, and whether theloss of intact glycocalyx is measurable in end organs. C57BL/6 mice were grouped as uninjured controls, 10% or 25% Total Body Surface Area (TBSA) scald burns. Blood and tissue sampling was performed over a specific time course. Plasma levels of shed syndecan-1, a marker of glycocalyx damage, were quantified by ELISA. Lung and spleen sections were stained with immunofluorescent anti-syndecan-1 antibodies to evaluate intact glycocalyx. Plasma syndecan-1 levels were higher in injured versus uninjured animals. Normalized levels of syndecan-1 in burned mice were significantly increased compared to hour 0 (p<0.05) at hours 4 and 8 post-injury in the 10% TBSA, and at hour 4 in the 25% TBSA group. Levels in the 10% and 25% TBSA groups peaked at hour 4 with fold change of 2.3 and 2.4 respectively. There was less pulmonary syndecan-1 immunostaining in burned animals compared to controls, and the levels inversely correlated with systemic shed syndecan- 1, beginning at hour 4 in the 10% TBSA injury group and at all time points in the 25% TBSA injury group, (0.27±0.06 and 0.14±0.04 respectively for hour 4). Similarly, there was less spleen syndecan-1 immunostaining in burned animals compared to controls at all time points. Burn injury causes shedding of syndecan-1 in a murine model, with levels correlated to injury severity and loss of the glycocalyx in lung and spleen. This work provides further insight into quantification and temporality of glycocalyx damage and systemic response to burn.

Les données concernant la dysfonction endothéliale après brûlure sont parcellaires. Les buts de cette étude étaient d'établir une corrélation entre la perte de glycocalyx et la gravité de la brûlure et si cette perte était mesurable au niveau des organes. Des souris C57BL/6 ont été réparties en groupes contrôle, brûlure 10% et brûlure 25% de SCT. Des prélèvements de sang et de tissus ont été réalisés à intervalles prédéterminés. Les taux plasmatiques de syndecan 1 (S1), marqueur de lésion du glycocalyx, ont été mesuré par méthode ELISA. Des échantillons de poumon et de rate ont été mis en présence d'anticorps anti S1, afin d'évaluer le glycocalyx intact. Les taux plasmatiques de S1 étaient plus élevés que ceux du groupe contrôle. Chez les souris brûlées sur 10% de SCT, les taux de S1 à 4h et 8 h étaient supérieurs au taux avant brûlure, ceci n'étant observé qu'à h4 chez les souris brûlées sur 25% de SCT. Le pic de S1 se produisait à h4, avec un rapport de x2,3 (10%) et x2,4 (25%) par rapport à la valeur de base. A partir de h4, on observait une baisse de complexes S1-antiS1 dans les poumons des souris brûlées sur 10% (0,27 +/- 0,06), inversement corrélée aux taux plasmatiques de S1. Cette observation se répétait lors de tous les dosages chez les 25% (0,14 +/- 0,04 à h4). Les mêmes constatations étaient faites sur les échantillons de rate. La brûlure cause des lésions du glycocalyx, parallèles à sa gravité. Ces travaux ouvrent le champ à des recherches futures sur les lésions du glycocalyx et la réponse inflammatoire aux brûlures.