A combination endovascular device:thrombectomy with localized hypothermia

描述（由申请人提供）：中风是美国第三大死亡原因和成人残疾的头号原因。缺血性卒中治疗的主要目标是快速恢复血液灌注。然而，研究表明，这种血流的恢复虽然对改善患者预后是必要的，但可能会对局部组织造成损伤。低温已被证明可以减少这种“再灌注损伤”。这项拟议研究的总体目标是使用治疗性低温来增强现有机械凝块清除装置的组织挽救能力，这些装置通过减少再灌注损伤来恢复灌注。我们提出的器械是一种冷却导引导管，其功能与传统导引导管相同，但具有血液冷却能力，可挽救存在再灌注损伤风险的缺血组织。具体目标：1.）设计一种冷却导引导管，可与现有的机械凝块清除装置一起使用，并可快速降低靶组织温度，2.）在体外脑模型中表征装置热流体性能，以及3.）在小动物初步研究中证明冷却导管可以安全有效地降低靶组织温度。为实现这些目标，将开展以下工作：热-流体建模、设计输入要求和可行性点、原型设计的开发、冷却剂压力-流动行为表征、模拟颅内血流的系统中每个原型的体外热-流体性能测试，体内试验表明，快速局部组织冷却是可行的，导管具有血液相容性，无明显损伤血管或组织。相关性：结合中风治疗疗法的技术创新-机械凝块清除和再灌注低温-可能产生协同效益，与单独使用任一技术的结果相比，可减少梗死面积并改善神经学结局。如果在I期研究中显示快速和安全的冷却是可行的，则II期研究将使用动物中风模型来研究疗效。 公共卫生相关性：中风是美国第三大死亡原因和成人残疾的头号原因。对于中风治疗，快速恢复血流已被证明可以改善结果，尽管一些专家发现再灌注损伤会减轻这些益处。FocalCool，LLC寻求使用新型冷却导引导管将血栓切除术和治疗性低温这两种技术联合收割机结合起来，从而最大限度地提高血流恢复的受益，同时最大限度地降低再灌注损伤的破坏性影响。

DESCRIPTION (provided by applicant): Stroke is the 3rd leading cause of death and number one cause of adult disability in the United States. The primary goal of ischemic stroke treatment is quickly restoring blood perfusion. However, studies have shown that this return of blood flow, while necessary to bettering patient outcome, can cause damage to local tissue. Hypothermia has been shown to decrease this "reperfusion injury". The overall goal of this proposed research is to use therapeutic hypothermia to augment the tissue salvage capabilities of existing mechanical clot removal devices that restore perfusion by reducing reperfusion injury. Our proposed device is a cooling guide catheter which will function identically to conventional guide catheters but with blood cooling capabilities to save ischemic tissue at risk of reperfusion injury. Specific Aims: 1.) Design a cooling guide catheter that can be used with existing mechanical clot removal devices and that can quickly reduce target tissue temperatures, 2.) characterize device thermal-fluid performance in an in vitro brain model, and 3.) demonstrate that the cooling catheter can safely and effectively decrease target tissue temperature in a small animal pilot study. To achieve these aims the following will be performed: thermal-fluid modeling, design input requirements and feasibility points, development of prototype designs, coolant pressure-flow behavior characterization, in vitro thermal-fluid performance testing for each prototype in system that mimics intracranial blood flow, and in vivo testing demonstrating that rapid localized tissue cooling is feasible and that the catheter is hemocompatibile with no significant damage to vessels or tissue. Relevance: The technological innovation of combining stroke treatment therapies - mechanical clot removal and reperfusion hypothermia - may yield synergistic benefits, resulting in reduced infarct size and improved neurological outcomes compared to outcomes using either technology separately. If fast and safe cooling is shown feasible in Phase I, Phase II would investigate efficacy using an animal stroke model. PUBLIC HEALTH RELEVANCE: Stroke is the 3rd leading cause of death and number one cause of adult disability in the United States. For stroke treatment, quickly restoring blood flow has been shown to improve outcome, although some experts have found reperfusion injury mitigates these benefits. FocalCool, LLC seeks to combine two technologies, thrombectomy and therapeutic hypothermia using a novel cooling guide catheter potentially maximizing the benefit of blood flow restoration while minimizing damaging effects of reperfusion injury.