The most common and potentially treatable cause of secondary neurological injury in this population in patients with aneurysmal subarachnoid hemorrhage (SAH) is delayed ischemic deficit (DID). This phenomenon 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 CBF reduction are the severe narrowing of intracranial arteries (vasospasm) and a loss of normal autoregulatory function in the distal circulation. Recent preliminary studies have shown that early administration of statins can reduce the incidence of DID and symptomatic arterial vasospasm This benefit may be due an increase in cerebral blood flow, autoregulatory responses to low flow, or non-hemodynamic mechanisms. The primary objective of this project is to investigate the effect of statin therapy on CBF in 50 patients with aneurysmal SAH who are randomized evenly to receive or not receive statins in a blinded design. We will measure and compare 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 will compare autoregulatory function between treatment groups at days 7 (Aim 2). PET measurements of Oxygen 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 of symptomatic vasospasm, incidence of arteriographic vasospasm, and ultimate neurological outcome. More detailed analyses of hemodynamic and metabolic data will also be performed, including comparisons between treatment groups in regional CBF, OEF, Cerebral Blood Volume (CSV, measured in order to calculate 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 a mitigation of large arterial narrowing. The information gain from this study will help us to better understand the mechanism of action of statins. This knowledge may be useful in the design of future studies with statins and 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 #
5P50NS055977-05
Application #
8375985
Study Section
Special Emphasis Panel (ZNS1-SRB-G)
Project Start
Project End
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
5
Fiscal Year
2012
Total Cost
$152,926
Indirect Cost
$61,775
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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