High levels of soluble VEGF receptor 1 early after trauma are associated with shock, sympathoadrenal activation, glycocalyx degradation and inflammation in severely injured patients: a prospective study

Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine

Pär I Johansson⁴  Claus F Larsen⁶  Michael Wanscher³  Karen-Lise Welling⁵  Anders Perner¹  Nis A Windeløv²  Anne Marie Sørensen⁶  Sisse R Ostrowski⁴ 

[1] Department of Intensive Care, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark;Department of Anesthesia, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark;Department of Cardiothoracic Anesthesia, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark;Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark;Department of Neurointensive Care, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark;The Trauma Centre, Centre of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, Copenhagen DK-2100, Denmark

关键词: Sympathoadrenal activation;    Catecholamines;    Adrenaline;    Syndecan-1;    sFlt-1;    sVEGFR1;    Soluble vascular growth factor receptor 1;    Glycocalyx;    Endothelial cells;    Endothelium;    Trauma;   

Others  :  826621
DOI  :  10.1186/1757-7241-20-27

 received in 2011-12-07, accepted in 2012-04-10,  发布年份 2012

【 摘 要 】

Background

The level of soluble vascular endothelial growth factor receptor 1 (sVEGFR1) is increased in sepsis and strongly associated with disease severity and mortality. Endothelial activation and damage contribute to both sepsis and trauma pathology. Therefore, this study measured sVEGFR1 levels in trauma patients upon hospital admission hypothesizing that sVEGFR1 would increase with higher injury severity and predict a poor outcome.

Methods

Prospective observational study of 80 trauma patients admitted to a Level I Trauma Centre. Data on demography, biochemistry, Injury Severity Score (ISS), transfusions and 30-day mortality were recorded and plasma/serum (sampled a median of 68 min (IQR 48-88) post-injury) was analyzed for sVEGFR1 and biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), tissue injury (histone-complexed DNA fragments, hcDNA), endothelial activation and damage (von Willebrand Factor Antigen, Angiopoietin-2, soluble endothelial protein C receptor, syndecan-1, soluble thrombomodulin (sTM)), coagulation activation/inhibition and fibrinolysis (prothrombinfragment 1 + 2, protein C, activated Protein C, tissue-type plasminogen activator, plasminogen activator inhibitor-1, D-dimer) and inflammation (interleukin-6). Spearman correlations and regression analyses to identify variables associated with sVEGFR1 and its predictive value.

Results

Circulating sVEGFR1 correlated with injury severity (ISS, rho = 0.46), shock (SBE, rho = -0.38; adrenaline, rho = 0.47), tissue injury (hcDNA, rho = 0.44) and inflammation (IL-6, rho = 0.54) (all p < 0.01) but by multivariate linear regression analysis only lower SBE and higher adrenaline and IL-6 were independent predictors of higher sVEGFR1. sVEGFR1 also correlated with biomarkers indicative of endothelial glycocalyx degradation (syndecan-1, rho = 0.67), endothelial cell damage (sTM, rho = 0.66) and activation (Ang-2, rho = 0.31) and hyperfibrinolysis (tPA, rho = 0.39; D-dimer, rho = 0.58) and with activated protein C (rho = 0.31) (all p < 0.01). High circulating sVEGFR1 correlated with high early and late transfusion requirements (number of packed red blood cells (RBC) at 1 h (rho = 0.27, p = 0.016), 6 h (rho = 0.27, p = 0.017) and 24 h (rho = 0.31, p = 0.004) but was not associated with mortality.

Conclusions

sVEGFR1 increased with increasing injury severity, shock and inflammation early after trauma but only sympathoadrenal activation, hypoperfusion, and inflammation were independent predictors of sVEGFR1 levels. sVEGFR1 correlated strongly with other biomarkers of endothelial activation and damage and with RBC transfusion requirements. Sympathoadrenal activation, shock and inflammation may be critical drivers of endothelial activation and damage early after trauma.

【 授权许可】

   
2012 Ostrowski et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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