title: Effect of delayed onset prostacyclin on markers of endothelial function and damage after subarachnoid hemorrhage.
abstract: 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.
  
  
  
  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.
  
  
  
  Ninety patients were randomized. Prostacyclin infusion influenced neither biomarkers of sympathoadrenal activation, endothelial activation and damage nor biomarkers of endothelial glycocalyx breakdown.
  
  
  
  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.
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark. mikkel.gybel-brask@regionh.dk.
authors.forename: Mikkel
authors.identifier: 0000-0002-5716-5899
authors.initials: M
authors.lastname: Gybel-Brask
authors.affiliation: Department of Neurosurgery, Neurocenter, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: Rune
authors.initials: R
authors.lastname: Rasmussen
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.|Department of Anesthesia, Center of Head and Orthopedics, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Stensballe
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.|Department of Surgery, University of Texas Health Medical School, Houston, TX, USA.|Center for Systems Biology, School of Engineering and Natural Sciences, University of Iceland, Reykjavík, Iceland.
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark.
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004730:Endothelium, Vascular / Q000378:metabolism; D011464:Epoprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D019276:Glycocalyx / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000188:drug therapy*
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D011464:Epoprostenol
keywords: Endothelium; Glycocalyx; Prostacyclin; Subarachnoid hemorrhage