title: Acute Effect of Intravenous Sildenafil on Cerebral Blood Flow in Patients with Vasospasm After Subarachnoid Hemorrhage.
abstract: The phosphodiesterase-5 inhibitor sildenafil has been shown to attenuate delayed cerebral ischemia (DCI) and improve neurologic function in experimental subarachnoid hemorrhage (SAH). We recently demonstrated that it could improve cerebral vasospasm (CVS) in humans after SAH. However, successful therapies for DCI must also restore cerebral blood flow (CBF) and/or autoregulatory capacity. In this study, we tested the effects of sildenafil on CBF in SAH patients at-risk for DCI.
  
  
  
  Six subjects with angiographically confirmed CVS received 30-mg of intravenous sildenafil (mean 9 ± 2 days after aneurysmal SAH). Each underwent (15)O-PET imaging to measure global and regional CBF at baseline and post-sildenafil.
  
  
  
  Mean arterial pressure declined by 10 mm Hg on average post-sildenafil (8 %, p = 0.01), while ICP was unchanged. There was no change in global CBF (mean 34.5 ± 7 ml/100g/min at baseline vs. 33.9 ± 8.0 ml/100g/min post-sildenafil, p = 0.84). The proportion of brain regions with low CBF (<25 ml/100g/min) was also unchanged after sildenafil infusion.
  
  
  
  Infusion of sildenafil does not lead to a change in global or regional perfusion despite a significant reduction in cerebral perfusion pressure. While this could reflect the ineffectiveness of sildenafil-induced proximal vasodilatation to alter brain perfusion, it also suggests that cerebral autoregulatory function was preserved in this group. Future studies should assess whether sildenafil can restore or enhance autoregulation after SAH.
authors.affiliation: Division of Neurocritical Care, Department of Neurology, Washington University in St. Louis, 660 S Euclid Avenue, St. Louis, MO, 63110, USA. dharr@neuro.wustl.edu.
authors.forename: Rajat
authors.identifier: 0000-0002-5167-5097
authors.initials: R
authors.lastname: Dhar
authors.affiliation: Department of Neurosurgery, Washington University in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Chad
authors.initials: C
authors.lastname: Washington
authors.affiliation: Division of Neurocritical Care, Department of Neurology, Washington University in St. Louis, 660 S Euclid Avenue, St. Louis, MO, 63110, USA.|Department of Neurosurgery, Washington University in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Diringer
authors.affiliation: Division of Neurocritical Care, Department of Neurology, Washington University in St. Louis, 660 S Euclid Avenue, St. Louis, MO, 63110, USA.|Department of Radiology, Washington University in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Allyson
authors.initials: A
authors.lastname: Zazulia
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Hussain
authors.initials: H
authors.lastname: Jafri
authors.affiliation: Division of Neurocritical Care, Department of Neurology, Washington University in St. Louis, 660 S Euclid Avenue, St. Louis, MO, 63110, USA.|Department of Neurosurgery, Washington University in St. Louis, St. Louis, MO, 63110, USA.|Department of Radiology, Washington University in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Derdeyn
authors.affiliation: Division of Neurocritical Care, Department of Neurology, Washington University in St. Louis, 660 S Euclid Avenue, St. Louis, MO, 63110, USA.|Department of Neurosurgery, Washington University in St. Louis, St. Louis, MO, 63110, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Zipfel
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000068677:Sildenafil Citrate / Q000008:administration & dosage / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D020301:Vasospasm, Intracranial / Q000178:diet therapy* / Q000209:etiology
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate
keywords: Cerebral blood flow; Phosphodiesterase; Sildenafil; Subarachnoid hemorrhage; Vasospasm