Abstract
BackgroundThe endothelial glycocalyx layer (EGL) is a key regulator of vascular permeability, cell adhesion, and inflammation. The EGL is primarily composed of syndecan-1, hyaluronic acid (HA), heparan sulfate (HS) and chondroitin sulfate (CS). While many studies have observed increased shedding of syndecan-1 during hemorrhagic shock, little is known about the shedding of other EGL components, and their effects on altered permeability and coagulation. We characterized shedding of all four primary components of the EGL, as well as the plasma’s effect on permeability and thrombin generation in a cohort of trauma patients.MethodsPlasma samples were collected from 5 healthy consented volunteers and 22 severely injured trauma patients upon admission to the emergency department. ELISA assays were performed to quantify shed HA, HS, CS and syndecan-1 in plasma. A colloid osmometer and Electric Cell-substrate Impedance Sensing (ECIS) system were used to measure plasma colloid osmotic pressure (COP) and cell permeability, respectively. Thrombin generation was measured using a calibrated automated thrombogram (CAT). Initial vital signs, routine laboratory values, and injury severity scores (ISS) were recorded. Non-parametric statistical tests were used to compare differences between groups.ResultsWe observed increased shedding of all four proteins in trauma patient plasma compared to healthy controls: 31.7 vs. 21.2 U/L of CS, 175.8 vs. 121.9 ng/ml of HS, 946.7 vs. 618.6 ng/ml of HA and 245.8 vs. 31.6 ng/ml of syndecan-1 (all p < 0.05). Patients with low plasma COP (≤16 mmHg) had significantly increased syndecan-1 and HA compared to those with normal COP, which corresponded to increased cell permeability via ECIS. CS and HS did not vary between COP groups. Lastly, patients with low COP displayed reduced peak thrombin generation of less than 250 nM on average (p < 0.05).ConclusionsGlycocalyx components were shed more in trauma patients compared to healthy controls in this cohort. However, only syndecan-1 and HA shedding were significantly higher in patients with reduced plasma COP. Thrombin generation was impaired in patients with low plasma COP. These data suggest that low plasma COP correlates well to glycocalyx degradation and thrombin loss following trauma, which consequently affect permeability and coagulation.
Highlights
The endothelial glycocalyx layer (EGL) is a key regulator of vascular permeability, cell adhesion, and inflammation
Patients in the low colloid osmotic pressure (COP) group were more severely injured as demonstrated by the higher injury severity scores (ISS), had worse pH and base excess levels and received more blood transfusions within 24 hours compared to the normal COP group (Table 1)
Glycocalyx shedding, catecholamines and endothelial permeability We observed significant increases in shedding of syndecan-1 and hyaluronic acid (HA) in trauma patients with low plasma COP compared to those with normal COP (Table 2)
Summary
The endothelial glycocalyx layer (EGL) is a key regulator of vascular permeability, cell adhesion, and inflammation. While many studies have observed increased shedding of syndecan-1 during hemorrhagic shock, little is known about the shedding of other EGL components, and their effects on altered permeability and coagulation. 50% of hemorrhagic deaths occur within 3–6 hours of injury [1]. Many of these deaths are considered potentially preventable with appropriate care and resuscitation. Recent efforts in resuscitation for massively injured patients have focused on restoring the blood volume lost, and ameliorating the inflammatory and coagulopathic responses, vascular permeability and endothelial dysfunction [2,3,4]. Endothelial dysfunction and vascular permeability (i.e. “capillary leak”) have been associated with increased morbidity and mortality; in particular, sepsis, multiorgan failure and hemorrhagic shock [5,6]
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