Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage

Michael N Diringer; Rajat Dhar; Michael Scalfani; Allyson R Zazulia; Michael Chicoine; William J Powers; Colin P Derdeyn

doi:10.1007/s12028-015-0233-7

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Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage

Journal article

Peer reviewed

Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage

Michael N Diringer, Rajat Dhar, Michael Scalfani, Allyson R Zazulia, Michael Chicoine, William J Powers and Colin P Derdeyn

Neurocritical care, Vol.25(1), pp.56-63

08/2016

DOI: 10.1007/s12028-015-0233-7

PMCID: PMC4930426

PMID: 26721259

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http://doi.org/10.1007/s12028-015-0233-7View

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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.

Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage

Cerebrovascular Circulation - drug effects

Simvastatin - administration & dosage

Humans

Middle Aged

Vasospasm, Intracranial - diagnostic imaging

Male

Brain Ischemia - prevention & control

Positron-Emission Tomography

Subarachnoid Hemorrhage - diagnostic imaging

Simvastatin - pharmacology

Vasospasm, Intracranial - prevention & control

Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology

Female

Aged

Homeostasis - drug effects

Brain Ischemia - diagnostic imaging

Subarachnoid Hemorrhage - drug therapy

Details

Title: Subtitle: Effect of High-Dose Simvastatin on Cerebral Blood Flow and Static Autoregulation in Subarachnoid Hemorrhage
Creators: Michael N Diringer - Department of Neurological Surgery, Washington University, St. Louis, MO, USA. diringerm@neuro.wustl.edu
Rajat Dhar - Department of Neurology, Washington University, Campus Box 8111, 660 S Euclid Ave, St Louis, MO, 63110, USA
Michael Scalfani - Kansas City University of Medicine and Biosciences, Kansas City, MO, USA
Allyson R Zazulia - Department of Radiology, Washington University, St. Louis, MO, USA
Michael Chicoine - Department of Neurological Surgery, Washington University, St. Louis, MO, USA
William J Powers - Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Colin P Derdeyn - Department of Radiology, Washington University, St. Louis, MO, USA
Resource Type: Journal article
Publication Details: Neurocritical care, Vol.25(1), pp.56-63
DOI: 10.1007/s12028-015-0233-7
PMID: 26721259
PMCID: PMC4930426
NLM abbreviation: Neurocrit Care
ISSN: 1541-6933
eISSN: 1556-0961
Publisher: United States
Grant note: P50 NS055977 / NINDS NIH HHS
Language: English
Date published: 08/2016
Academic Unit: Neurology; Radiology; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984020769002771

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