Release of Hyaluronan in Aneurysmal Subarachnoid Hemorrhage and Cerebral Vasospasm: A Pilot Study Indicating a Shedding of the Endothelial Glycocalyx.

Background: This pilot study investigated plasma concentrations of hyaluronan, heparan sulfate, and syndecan-1 as possible biomarkers for glycocalyx integrity after aneurysmal subarachnoid hemorrhage (aSAH).
Methods: Daily blood samples for biomarker assay were obtained in aSAH patients on the intensive care unit stay and compared with samples from a historic cohort of 40 healthy controls. In post hoc subgroup analyses in patients with and without cerebral vasospasm, we explored the influence of aSAH-related cerebral vasospasm on biomarker levels.
Results: A total of 18 aSAH patients and 40 historic controls were included in the study. Median (interquartile range) plasma levels of hyaluronan were higher in aSAH patients compared with controls (131 [84 to 179] vs. 92 [82 to 98] ng/mL, respectively; P=0.009), whereas heparan sulfate (mean±SD: 754±428 vs. 1329±316 ng/mL; P<0.001) and syndecan-1 (median: 23 [17 to 36] vs. 30 [23 to 52] ng/mL; P=0.02) levels were lower. Patients who developed vasospasm had significantly higher median hyaluronan concentrations at day 7 (206 [165 to 288] vs. 133 [108 to 164] ng/mL, respectively; P=0.009) and at day of first vasospasm detection (203 [155 to 231] vs. 133 [108 to 164] ng/mL, respectively; P=0.01) compared with those without vasospasm. Heparan sulfate and syndecan-1 concentrations were similar in patients with and without vasospasm.
Conclusions: The increased plasma concentrations of hyaluronan after aSAH suggest selective shedding of this component of the glycocalyx. Increased levels of hyaluronan in patients with cerebral vasospasm, underlines a potential role for hyaluronan in vasospasm processes.
Competing Interests: A.I. reports research grants from the Koeln Fortune Program, Faculty of Medicine, University of Cologne, Germany (216/2016) and from the German Research Council (DFG; RA 2838/2-1). T.A. reports research funding from Aerogen, B. Braun Foundation, CIOKoeln Bonn, Corpuls, CytoSorbents Europe, Medtronic and PULSION Medical Systems, Federal Ministry for Economic Affairs and Energy. The remaining authors have no conflicts of interest to disclose.
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