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的可治疗原因是 动脉瘤性蛛网膜下腔出血(SAH)患者为迟发性脑缺血缺损症(DID)。这 这种现象本质上是脑血流量(CBF)降低到临界缺血阈值以下， 发生在出血发生后的几天。CBF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)和失去正常的自我调节 在远端循环中起作用。最近的初步研究表明，早期服用他汀类药物 可以减少DID和症状性动脉血管痉挛的发生率，这一好处可能是由于增加了 在脑血流中，对低流量或非血流动力学机制的自动调节反应。初级阶段 目的观察他汀类药物治疗对50例动脉瘤患者脑血流量的影响。 SAH患者采用盲法随机分组，接受或不接受他汀类药物治疗。我们将衡量和 用正电子发射断层扫描比较两组蛛网膜下腔出血后的整体脑血流 (PET)在两个时间点：在SAH发病后3至5天和第7天再次(目标1)。我们会 在第7天比较治疗组之间的自我调节功能(目标2)。宠物的测量 在基线和第7天测定氧摄取分数(OEF)，并进行组间比较 (目标3)。次要目标包括比较两个治疗组之间的发病率 症状性血管痉挛、动脉造影血管痉挛的发生率以及最终的神经学结果。更多 还将对血液动力学和代谢数据进行详细分析，包括比较 治疗组之间在局部CBF、OEF、脑血容量(CSV)方面进行测量，以 计算有或无动脉造影血管痉挛的动脉区域的OEF)和自动调节功能。 我们将确定他汀类药物是否能改善动脉瘤性蛛网膜下腔出血患者的脑血流。 这种改善，如果存在的话，可能是由于基础脑血流量的改善，自动调节功能的改善，或者 大动脉狭窄的缓解。从这项研究中获得的信息将有助于我们更好地理解 他汀类药物的作用机制。这一知识可能对他汀类药物未来研究的设计有用 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.