Effect of Statins on Cerebral Blood Flow after Subarachnoid Hemorrhage (SAH)

在这一人群中，继发性神经损伤的最常见和潜在可治疗的原因是 蛛网膜下腔出血（SAH）是一种迟发性缺血性脑损伤（DID）。这 这种现象基本上是脑血流量（CBF）降低到临界缺血阈值以下， 发生在出血开始后数天。CBF中涉及的两个重要生理过程 减少是颅内动脉严重狭窄（血管痉挛）和正常的自动调节功能丧失 在远端循环中发挥作用。最近的初步研究表明，早期服用他汀类药物 可降低DID和症状性动脉血管痉挛的发生率。 在脑血流中，对低流量的自动调节反应，或非血液动力学机制。主 本课题的目的是研究他汀类药物治疗对50例脑梗死患者脑血流的影响。 SAH患者随机平均接受或不接受他汀类药物治疗。我们将测量， 使用正电子发射断层扫描比较两个治疗组之间SAH后的总体CBF (PET)在两个时间点：SAH发作后3 - 5天和第7天。(Aim 1）。我们将 在第7天比较治疗组之间的自动调节功能（目的2）。PET测量 还将在基线和第7天时进行氧摄取分数（OEF）测定，并进行组间比较 (Aim 3）。次要目的包括比较两个治疗组之间的 症状性血管痉挛、动脉造影性血管痉挛的发生率和最终的神经学结局。更 还将对血流动力学和代谢数据进行详细分析，包括比较 治疗组之间的局部CBF、OEF、脑血容量（CSV，测量以 计算OEF）和有和无动脉造影性血管痉挛的动脉区域的自动调节功能。 我们将确定他汀类药物治疗是否能改善蛛网膜下腔出血患者的CBF。 这种改善（如果存在）可能是由于基础CBF改善、自身调节功能改善或 缓解大动脉狭窄。从这项研究中获得的信息将有助于我们更好地了解 他汀类药物的作用机制。这一知识可能有助于设计未来的研究与他汀类药物 以及针对类似机制的其他疗法的开发。

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.