title: Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage.
abstract: Statins may promote vasodilation following subarachnoid hemorrhage (SAH) and improve the response to blood pressure elevation. We sought to determine whether simvastatin increases cerebral blood flow (CBF) and alters the response to induced hypertension after SAH.
  
  
  
  Statin-naïve patients admitted <72 h after WFNS ≥2 aneurysmal SAH were randomly assigned to 80 mg simvastatin/day or placebo for 21 days. Regional CBF was measured with quantitative (15)O PET on SAH day 7-10 before and after raising mean arterial pressure (MAP) 20-25 %. Autoregulatory index (AI) was calculated as the ratio of % change in resistance (MAP/CBF) to % change in MAP. Angiography was performed within 24 h of PET. Results are presented as simvastatin vs. placebo.
  
  
  
  Thirteen patients received simvastatin and 12 placebo. Clinical characteristics were similar. Moderate or severe angiographic vasospasm occurred in 42 vs. 45 % and delayed cerebral ischemia in 14 vs. 55 % (p = 0.074). During PET studies, MAP (110 ± 10 vs. 111 ± 12), global CBF (41 ± 12 vs. 43 ± 13), and CVR (2.95 ± 1.0 vs. 2.81 ± 1.0) did not differ at baseline. When MAP was raised to 135 ± 7 mm Hg vs. 137 ± 15, global CBF did not change. Global AI did not differ (107 ± 59 vs. 0. 89 ± 52 %, p = 0.68). CBF did not change in regions with low baseline flow or in regions supplied by vessels with angiographic vasospasm in either group. Six-month modified Rankin Scale scores did not differ.
  
  
  
  Our data indicate that initiation of therapy with high-dose simvastatin does not alter baseline CBF or response to induced hypertension.
authors.affiliation: Department of Neurology, Washington University, Campus Box 8111, 660 S Euclid Ave, St Louis, MO, 63110, USA. diringerm@neuro.wustl.edu.|Department of Neurological Surgery, Washington University, St. Louis, MO, USA. diringerm@neuro.wustl.edu.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Diringer
authors.affiliation: Department of Neurology, Washington University, Campus Box 8111, 660 S Euclid Ave, St Louis, MO, 63110, USA.
authors.forename: Rajat
authors.initials: R
authors.lastname: Dhar
authors.affiliation: Kansas City University of Medicine and Biosciences, Kansas City, MO, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Scalfani
authors.affiliation: Department of Neurology, Washington University, Campus Box 8111, 660 S Euclid Ave, St Louis, MO, 63110, USA.|Department of Radiology, Washington University, St. Louis, MO, USA.
authors.forename: Allyson R
authors.initials: AR
authors.lastname: Zazulia
authors.affiliation: Department of Neurological Surgery, Washington University, St. Louis, MO, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Chicoine
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Powers
authors.affiliation: Department of Neurology, Washington University, Campus Box 8111, 660 S Euclid Ave, St Louis, MO, 63110, USA.|Department of Neurological Surgery, Washington University, St. Louis, MO, USA.|Department of Radiology, Washington University, St. Louis, MO, USA.
authors.forename: Colin P
authors.initials: CP
authors.lastname: Derdeyn
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000000981:diagnostic imaging / Q000517:prevention & control*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D013345:Subarachnoid Hemorrhage / Q000000981:diagnostic imaging / Q000188:drug therapy*; D020301:Vasospasm, Intracranial / Q000000981:diagnostic imaging / Q000517:prevention & control*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin
keywords: Blood pressure; Delayed cerebral ischemia; Induced hypertension; Positon emission tomography; Vasopressors; Vasospasm