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

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.