The most common and potentially treatable cause of secondary neurological injury in this population inpatients with aneurysmal subarachnoid hemorrhage (SAH) is delayed ischemic deficit (DID). Thisphenomenon is fundamentally a reduction of cerebral blood flow (CBF) below critical ischemic thresholds,occurring days after the onset of hemorrhage. Two important physiological processes involved in the CBFreduction are the severe narrowing of intracranial arteries (vasospasm) and a loss of normal autoregulatoryfunction in the distal circulation. Recent preliminary studies have shown that early administration of statinscan reduce the incidence of DID and symptomatic arterial vasospasm This benefit may be due an increasein cerebral blood flow, autoregulatory responses to low flow, or non-hemodynamic mechanisms. The primaryobjective of this project is to investigate the effect of statin therapy on CBF in 50 patients with aneurysmalSAH who are randomized evenly to receive or not receive statins in a blinded design. We will measure andcompare global CBF after SAH between the two treatment groups using Positron Emission Tomography(PET) at two time points: between 3 and 5 days after onset of SAH and again at day 7.
(Aim 1). We willcompare autoregulatory function between treatment groups at days 7 (Aim 2). PET measurements ofOxygen Extraction Fraction (OEF) will also be made at baseline and 7 days and compared between groups(Aim 3). Secondary aims include the comparison between the two treatment groups of the incidence ofsymptomatic vasospasm, incidence of arteriographic vasospasm, and ultimate neurological outcome. Moredetailed analyses of hemodynamic and metabolic data will also be performed, including comparisonsbetween treatment groups in regional CBF, OEF, Cerebral Blood Volume (CSV, measured in order tocalculate OEF) and autoregulatory function for arterial territories with and without arteriographic vasospasm.We will determine if statin therapy improves CBF in patients with aneurysmal subarachnoid hemorrhage.This improvement, if present, may be due to improved basal CBF, improved autoregulatory function, or amitigation of large arterial narrowing. The information gain from this study will help us to better understandthe mechanism of action of statins. This knowledge may be useful in the design of future studies with statinsand in the development of other therapies aimed at similar mechanisms.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
1P50NS055977-01A2
Application #
7524053
Study Section
Special Emphasis Panel (ZNS1-SRB-G (24))
Project Start
Project End
Budget Start
2008-07-01
Budget End
2009-04-30
Support Year
1
Fiscal Year
2008
Total Cost
$111,834
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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