Therapeutic Window for Acute Stroke Therapy

我们建议加州大学圣地亚哥分校卒中中心(UCSD)开设一个专门的急性卒中转化研究项目(SPOTRIAS)。核心设施和项目将达到SPOTRIAS的目标，增加接受溶栓治疗的患者数量，特别是那些在中风后2小时内接受治疗的患者。为了实现这一目标，我们提供了4个相互关联的项目。1)为了寻找一种简单的急性卒中的血清标志物，我们将表征急性卒中患者的游离脂肪酸(FFA)反应，包括时间进程。我们将确定FFA水平是否与不同的中风结局相关，并试图区分缺血和常见的模拟物。我们将描述与有效的溶栓相关的FFA反应。2)在第一阶段试验中，通过研究卒中后3-6小时开始的溶栓，结合24小时的血管内降温，利用低体温延长溶栓时间窗。我们假设低温对这类患者是安全的。我们将继续进行第二阶段的试验，以证明低温可以降低出血率并改善3到6小时溶栓患者的预后。3)使用非侵入性的床边试验-增强经颅超声，以确定溶栓前后的血管闭塞和灌注缺陷。我们将测试超声波是否可以区分中风和模拟中风，并从2小时内出现轻度或波动缺陷的患者中确定潜在的治疗候选对象。4)确定新型宽带无线互联网 这项技术将允许加州大学圣地亚哥分校卒中团队的教职员工通过在圣地亚哥的远程急诊科安装音频/视频会诊功能，在偏远的医院指导溶栓治疗。紧急会诊可能会增加2小时溶栓治疗的数量。这些项目建立在加州大学圣地亚哥分校卒中中心的核心设施上，其中包括一支全国认可的卒中团队、一个培训计划、一个数据收集和统计分析单位以及一个标本收集和存储设施。所有需要的团队、协作和设施都已就位。SPOTRIAS计划将允许我们加强和启动转化性研究，最终将通过在2小时内治疗更多患者并找到以后治疗更多患者的方法来使中风患者受益。

We propose a Specialized Program of Translational Research in Acute Stroke (SPOTRIAS) at the University of California, San Diego, Stroke Center (UCSD). The Core facilities and projects will meet SPOTRIAS target goals, increasing the number of thrombolytic-treated patients, particularly those treated within 2 hours following stroke. To achieve this, we offer 4 inter-related projects. 1) To find a simple, serum marker of acute stroke, we will characterize the free fatty acid (FFA) response in acute stroke patients, including the time course. We will determine whether FFA levels correlate with various stroke outcomes, and attempt to distinguish ischemia from common mimics. We will characterize the FFA response associated with effective thrombolysis. 2) To use hypotherrnia to prolong the time window for thrombolysis in a Phase 1 trial, by studying thrombolysis beginning 3 to 6 hours following stroke onset, combined with 24 hours of intravascular cooling. We hypothesize that hypothermia will be safe in such patients. We will proceed to a Phase 2 trial to show that hypothermia reduces hemorrhage rates and improves outcomes in 3 to 6 hour thrombolysis patients. 3) To use a non-invasive, bedside test---contrast enhanced transcranial ultrasoundmto identify vascular occlusion and perfusion defects before and after thrombolysis. We will test whether ultrasound may separate stroke from mimics, and identify potential treatment candidates from among patients with mild or fluctuating deficits presenting within 2 hours. 4) To determine whether novel broadband wireless Internet technology will allow UCSD Stroke Team faculty to direct thrombolysis at remote hospitals by placing audio/video consultation capability at remote Emergency Departments in San Diego. Acute consults may increase the number of 2-hour thrombolytic treatments. These projects are built on the core facilities of the UCSD Stroke Center, which include a nationally recognized stroke team, a training program, a data collection and statistical analysis unit, and a specimen collection and storage facility. All of the needed teams, collaborations, and facilities are in place. The SPOTRIAS program will allow us to enhance and initiate translational research that ultimately will benefit stroke patients by treating more patients under 2 hours, and finding ways to treat additional patients later.