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Effect of delayed onset prostacyclin on markers of endothelial function and damage after subarachnoid hemorrhage

  • Original Article - Vascular
  • Published:
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Abstract

Background

Subarachnoid hemorrhage (SAH) is a neurological emergency. Delayed ischemic neurological deficit is one of the main causes of poor outcome after SAH and is probably caused, at least in part, by cerebral vasospasm. The pathophysiology of this is multifaceted, but endothelial damage and activation as well as glycocalyx damage have been implicated. Prostacyclin has been shown to protect damaged and activated endothelium and to facilitate glycocalyx repair. We investigated biomarkers of endothelial activation and damage in patients with SAH randomized to 5 days prostacyclin infusion or placebo.

Methods

Patients with aneurysmal SAH managed by coiling or surgery, and a World Federation of Neurological Surgeons score between 1 and 4, and Fisher grade 3 or 4, were treated with a continuous low-dose intravenous prostacyclin infusion or placebo initiated on day 5 and discontinued on day 10 after SAH. Blood samples were drawn from the patients before, during and after prostacyclin/placebo infusion. Soluble biomarkers of endothelial cell activation (sE-selectin, sVE-cadherin) and damage (sTM), glycocalyx damage (syndecan-1) and sympathoadrenal activation (adrenaline, noradrenaline), were measured by ELISA.

Results

Ninety patients were randomized. Prostacyclin infusion influenced neither biomarkers of sympathoadrenal activation, endothelial activation and damage nor biomarkers of endothelial glycocalyx breakdown.

Conclusions

We did not find any effects on markers of sympathoadrenal activation, endothelial damage and activation, or glycocalyx degradation of delayed onset prostacyclin infusion compared to placebo. Further trials investigating early onset endothelial repair using prostacyclin are warranted.

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Acknowledgements

We acknowledge the technical assistance of Marie Helena Stjernkvist and Mehwish Jubeen Hussain for analysis of biomarkers in this study.

The trial was funded by the Copenhagen University Hospital research fund, a non-profit organization with no influence on the trial protocol, conduct or analysis.

Author information

Authors and Affiliations

  1. Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Mikkel Gybel-Brask, Jakob Stensballe, Pär I. Johansson & Sisse R. Ostrowski

  2. Department of Neurosurgery, Neurocenter, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark

    Rune Rasmussen

  3. Department of Anesthesia, Center of Head and Orthopedics, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark

    Jakob Stensballe

  4. Department of Surgery, University of Texas Health Medical School, Houston, TX, USA

    Pär I. Johansson

  5. Center for Systems Biology, School of Engineering and Natural Sciences, University of Iceland, Reykjavík, Iceland

    Pär I. Johansson

Authors
  1. Mikkel Gybel-Brask
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  2. Rune Rasmussen
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  3. Jakob Stensballe
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  4. Pär I. Johansson
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  5. Sisse R. Ostrowski
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Corresponding author

Correspondence to Mikkel Gybel-Brask.

Ethics declarations

Ethical standards

This study has been approved by the Danish Ethical Committee on Human Research (ref. no. H-1-2011-087), the Danish Medicines Agency (EudraCT 2011–002798-5), and registered on clinicaltrials.gov (ref. no. NCT01447095), and it has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

All patients gave their informed consent prior to their inclusion in the study.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Additional information

Clinical Trials Registration, Unique Indentifier: NCT01447095

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Gybel-Brask, M., Rasmussen, R., Stensballe, J. et al. Effect of delayed onset prostacyclin on markers of endothelial function and damage after subarachnoid hemorrhage. Acta Neurochir 159, 1073–1078 (2017). https://doi.org/10.1007/s00701-017-3168-2

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  • DOI: https://doi.org/10.1007/s00701-017-3168-2

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