Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients.

Abstract

BACKGROUND:

The 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.

METHODS:

Plasma 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.

RESULTS:

We 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).

CONCLUSIONS:

Glycocalyx 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.

• Authors: Elaheh Rahbar, Jessica C Cardenas, Gyulnar Baimukanova, Benjamin Usadi, Roberta Bruhn, Shibani Pati, Sisse R Ostrowski, Pär I Johansson, John B Holcomb, Charles E Wade
• Journal: Journal of translational medicine (J Transl Med) Vol. 13 Pg. 117 (Apr 12 2015) ISSN: 1479-5876 [Electronic] England
• PMID: 25889764 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catecholamines
• Thrombin

Topics

• Adult
• Capillary Permeability
• Case-Control Studies
• Catecholamines (metabolism)
• Endothelium, Vascular (metabolism)
• Enzyme-Linked Immunosorbent Assay
• Female
• Glycocalyx (metabolism)
• Humans
• Male
• Middle Aged
• Prospective Studies
• Severity of Illness Index
• Thrombin (biosynthesis)
• Wounds and Injuries (metabolism, physiopathology)