title: Effect of acute hypobaric hypoxia on the endothelial glycocalyx and digital reactive hyperemia in humans.
abstract: BACKGROUND
  Hypoxia is associated with increased capillary permeability. This study tested whether acute hypobaric hypoxia involves degradation of the endothelial glycocalyx.
  
  
  METHODS
  We exposed 12 subjects to acute hypobaric hypoxia (equivalent to 4500 m for 2-4 h) and measured venous blood concentrations of biomarkers reflecting endothelial and glycocalyx degradation (catecholamines, syndecan-1, soluble CD40 ligand, protein C, soluble thrombomodulin, tissue-type plasminogen activators, histone-complexed DNA fragments, and nitrite/nitrate). Endothelial function was assessed by the hyperemic response to brachial artery occlusion by peripheral arterial tonometry.
  
  
  RESULTS
  Compared with normoxic baseline levels, hypoxia increased concentrations of syndecan-1 from 22 (95% confidence interval: 17-27) to 25 (19-30) ng/ml (p < 0.02) and protein C from 76 (70-83)% to 81 (74-88)% (p < 0.02). Nitrite/nitrate decreased from 23 (18-27) μM at baseline to 19 (14-24) μM and 18 (14-21) μM in hypoxia and recovery, respectively (p < 0.05). Other biomarkers remained unchanged. The post-occlusion/pre-occlusion ratio (reactive hyperemia index, RHI) decreased from 1.80 (1.52-2.07) in normoxia to 1.62 (1.28-1.96) after 2-4 h of hypobaric hypoxia and thereafter increased to 2.43 (1.99-2.86) during normoxic recovery (p < 0.01).
  
  
  CONCLUSIONS
  The increase in syndecan-1 and protein C suggests that acute hypobaric hypoxia produces a minor degree of glycocalyx degradation and overall cellular damage. After hypoxia RHI rebounded to higher than baseline levels suggesting improved endothelial functionality.
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, The Diagnostic Centre, Copenhagen University Hospital (Rigshospitalet) Copenhagen, Denmark ; Department of Surgery, University of Texas Medical School Houston, TX, USA.
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.affiliation: Department of Neuroanaesthesia, The Neuroscience Centre, Copenhagen University Hospital (Rigshospitalet) Copenhagen, Denmark.
authors.forename: Anita
authors.initials: A
authors.lastname: Bergström
authors.affiliation: BrainLab, Department of Neuroscience and Pharmacology, University of Copenhagen Copenhagen, Denmark.
authors.forename: Niels J
authors.initials: NJ
authors.lastname: Aachmann-Andersen
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, The Diagnostic Centre, Copenhagen University Hospital (Rigshospitalet) Copenhagen, Denmark.
authors.forename: Martin A S
authors.initials: MA
authors.lastname: Meyer
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, The Diagnostic Centre, Copenhagen University Hospital (Rigshospitalet) Copenhagen, Denmark.
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
authors.affiliation: Department of Nutrition, Exercise and Sport, University of Copenhagen Copenhagen, Denmark.
authors.forename: Nikolai B
authors.initials: NB
authors.lastname: Nordsborg
authors.affiliation: Department of Neuroanaesthesia, The Neuroscience Centre, Copenhagen University Hospital (Rigshospitalet) Copenhagen, Denmark ; BrainLab, Department of Neuroscience and Pharmacology, University of Copenhagen Copenhagen, Denmark.
authors.forename: Niels V
authors.initials: NV
authors.lastname: Olsen
keywords: endothelium; glycocalyx; hypoxia; nitrite/nitrate; peripheral arterial tonometry; protein C; syndecan-1