Remote Ischemic Conditioning: A collateral therapeutic and neuroprotectant

溶栓和血管内血栓切除术（ET）仍然是仅有的两种FDA批准的缺血性卒中治疗方法。尽管ET有效，但50%的患者在3个月时仍然残疾。需要溶栓和ET的辅助治疗，以提供“桥接神经保护”并改善侧支血流。由于侧支循环的存在是ET预后的主要预测因素，因此一种有前途的新治疗途径是开发“侧支循环疗法”。远程缺血预处理（RIC）是对肢体血压（BP）袖带进行简单安全的重复充气-放气，可减少梗死面积，改善功能结局，并改善急性卒中的脑和侧支血流。RIC可以在救护车、直升机、急诊室、介入室、医院或康复机构中进行，因此是ET的理想预防性治疗。我们的总体假设是，RIC是一种廉价、通用、安全和有效的单独治疗方法，也是与tPA联合治疗的方法。急性卒中中的ET。我们的目标包括：目标1：与协调中心和指导委员会合作，制定标准操作规程、卒中模型的选择、随机化和设盲方法、样本量估计和数据共享方法。在一项临床前多中心随机对照试验（pRCT）中，比较RIC和其他5种药物/干预措施在最佳给药方案下作为啮齿动物急性卒中模型再灌注的连续治疗设计并推进最有效的干预措施进入II期临床试验。

Thrombolysis and endovascular thrombectomy (ET), remain the only two FDA-approved ischemic stroke therapies. Despite the efficacy of ET, 50% of the patients remain disabled at 3 months. Adjunctive therapies to thrombolysis and ET are needed that provide “bridging neuroprotection” and improve collateral blood flow. Since presence of collaterals is a major predictor of outcome with ET, a promising new therapeutic avenue is development of “collateral therapeutics.” Remote ischemic conditioning (RIC), the simple and safe repetitive inflation-deflation of a blood pressure (BP) cuff on the limb, reduces infarct size, improves functional outcome, and improves cerebral and collateral blood flow in acute stroke. RIC can be administered in the ambulance, the helicopter, the Emergency Department, in the interventional suite, and in the hospital or rehabilitation facility and is therefore an ideal adjunctive treatment to ET. Our overall hypothesis is that RIC is an inexpensive, versatile, safe and effective therapy alone and in combination with tPA./ET in acute stroke. Our aims include: Aim 1: Working with the Coordinating Center and the Steering Committee, develop standard operation procedures, choice of stroke model, methods of randomization and blinding, sample size estimation and methods of data sharing Aim 2: Compare RIC and 5 other agents/interventions at optimal dosing regimens as adjunctive therapies to reperfusion in rodent acute stroke models in a pre-clinical multicenter randomized controlled trial (pRCT) design and advance the most effective intervention into phase II clinical trial.