Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients

Journal of Translational Medicine

Charles E Wade⁵  John B Holcomb⁵  Pär I Johansson³  Sisse R Ostrowski³  Shibani Pati¹  Roberta Bruhn²  Benjamin Usadi²  Gyulnar Baimukanova²  Jessica C Cardenas⁵  Elaheh Rahbar⁴ 

[1] Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA;Blood Systems Research Institute, San Francisco, CA, USA;Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark;Department of Biomedical Engineering, Wake Forest University, 575 N. Patterson Ave, Suite 120, Winston-Salem 27101, NC, USA;Department of Surgery, Center for Translational Injury Research, University of Texas Health Science Center, Houston, TX, USA

关键词: Thrombin;    Trauma;    Permeability;    Syndecan-1;    Hyaluronic acid;    COP;    Glycocalyx;   

Others  :  1207757
DOI  :  10.1186/s12967-015-0481-5

 received in 2014-10-23, accepted in 2015-04-01,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Rahbar et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

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