Abstract 206: Characterization of Glycocalyx Shedding in Trauma Patients

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Background: The endothelial glycocalyx layer is a key regulator of vascular permeability, cell adhesion, and inflammation. This organized mesh of membranous proteins 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, none have investigated the other three components of the glycocalyx in response to injury. In this study, we characterized the shedding of all four primary components of the glycocalyx in trauma patients. Methods and Results: Plasma samples were collected from five healthy consented volunteers and 20 severely injured trauma patients upon admission to the emergency department. ELISA assays were performed to determine amounts of shed HA, HS, CS and syndecan-1 in plasma. Oncotic pressure and serum protein levels were also measured. Initial vital signs, routine laboratory values, and injury severity scores (ISS) were recorded. ANOVA was used to compare statistical significance between groups; median values are reported. We observed increased shedding of all four components compared to normal controls: 32.3 vs. 23.1 U/L of CS, 180 vs. 136.1 ng/ml of HS, 29.2 vs. 11.6 ng/ml of HA and 45.8 vs. 27 ng/ml of syndecan-1 (p<0.05). Further, we found a correlation between ISS, plasma oncotic pressure, shed syndecan-1 and HA levels. Patients with reduced oncotic pressure (<16 mmHg) had exponentially increased shedding of syndecan-1 (221.7 vs. 34.6 ng/ml, p=0.03) and HA (146 vs. 23.4 ng/ml, p=0.02), which correlated to higher ISS (34 vs. 19, p=0.04) compared to those with normal oncotic pressures. Surprisingly, CS and HS levels did not correlate with ISS and remained constant for all trauma patients. Conclusions: All four components of the glycocalyx are shed in trauma patients compared to normal controls. However, only syndecan-1 and HA shedding strongly correlated with increased severity of anatomic injury and reduced plasma oncotic pressure. These data suggest that syndecan-1 and HA could play a role in the restoration of the glycocalyx during hemorrhagic shock and resuscitation, especially in more severely injured patients who experience glycocalyx shedding and increased membrane permeability.