TY - JOUR

T1 - Effect of acute hypobaric hypoxia on the endothelial glycocalyx and digital reactive hyperemia in humans

AU - Johansson, Pär I

AU - Bergström, Anita

AU - Aachmann-Andersen, Niels Jacob

AU - Meyer, Martin A S

AU - Ostrowski, Sisse Rye

AU - Nordsborg, Nikolai Baastrup

AU - Olsen, Niels Vidiendal

N1 - CURIS 2014 NEXS 378

PY - 2014

Y1 - 2014

N2 - INTRODUCTION: 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.

AB - INTRODUCTION: 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.

U2 - 10.3389/fphys.2014.00459

DO - 10.3389/fphys.2014.00459

M3 - Journal article

C2 - 25505423

VL - 5

JO - Frontiers in Physiology

JF - Frontiers in Physiology

SN - 1664-042X

M1 - 459

ER -