Attenuating reperfusion injury with combined hypothermia and gradual reperfusion.

描述（由申请人提供）：心脏病发作期间的主要护理目标是快速恢复血液灌注。然而，再灌注是自相矛盾的，虽然它使器官存活;它也使破坏性的生化过程。虽然已经研究了许多急性心肌梗死（AMI）的预防性治疗，但需要创新的联合治疗。低温和逐渐再灌注都显示出在缺血-再灌注后保存心脏组织方面的益处。这项工作的总体目标是将这两种技术联合收割机用于改善AMI结果的附加或协同益处。具体目标：1）开发一种组合治疗装置，其精确控制再灌注流量以及组织冷却和复温。2)证明所提出的联合治疗技术能够仔细、安全地控制再灌注和组织温度，并在大型动物平移缺血-再灌注模型中提供组织挽救获益。为实现目标1，将开发一组固定的设计输入要求和可行性点，将创建5个充分表征和稳健的器械原型，以备体内试验，并将根据组织冷却能力和体内试验的潜在有效性选择最佳操作方案。对于目标#2，将在大型动物缺血-再灌注模型中测试最佳操作方案。这些结果将表明该方案在减少组织损伤方面是安全有效的，证明存在临床相关组织挽救的可能性。相关性：美国每年约有11万人接受紧急血管成形术。根据AHA 2010年的统计数据，20%的首次心脏病发作患者在事件发生后一年内死亡。FocalCool，LLC的目标是通过安全有效地使用受控再灌注低温来减少再灌注损伤，从而改善急诊血管成形术患者的结局。如果I期旨在证明关节技术的安全性、冷却能力和组织挽救可行性，则II期工作将冻结GLP动物试验和IDE申请的设计，并在转化临床前模型中证明组织挽救的有效性。

DESCRIPTION (provided by applicant): The primary care goal during a heart attack is to quickly restore blood perfusion. Reperfusion, however, is paradoxical, while it enables organ survival; it also enables destructive biochemical processes. While numerous adjunctive therapies for acute myocardial infarctions (AMI) have been studied, innovative combination therapies are needed. Both hypothermia and gradual reperfusion have shown benefit in terms of saving heart tissue following ischemia-reperfusion. The overall goal of this work is to combine these two techniques for additive and perhaps synergistic benefits for improving AMI outcomes. Specific Aims: 1) Develop a combination therapy device that precisely controls reperfusion flow as well as tissue cooling and re-warming. 2) Demonstrate that the proposed combination therapy technology has the ability to carefully and safely control both reperfusion and tissue temperature and provides tissue salvage benefit in a large animal translational ischemia-reperfusion model. To achieve aim #1, a fixed set of design input requirements and feasibility points will be developed, five fully characterized and robust device prototypes will be created ready for in vivo testing, and an optimal operational protocol based on tissue cooling ability and potential efficacy for in vivo testing will be selected. For aim #2, the optimal operational protocl will be tested in a large animal ischemia-reperfusion model. These results will show that the protocol is safe and effective at reducing tissue damage, demonstrating that there is a potential for clinically relevant tissue salvage. Relevance: Approximately 110,000 people each year in the U.S. have an emergency angioplasty procedure. According to the AHA 2010 Statistics, 20% of first time heart attack victims die within one year of the event. FocalCool, LLC's goal is to improve emergency angioplasty patient outcomes by reducing reperfusion injury through safe and effective use of controlled reperfusion hypothermia. If Phase I goals to demonstrate safety, cooling ability, and tissue salvage feasibility of the joint technology are successful, Phase II wok will freeze the design for GLP animal testing and an IDE application and demonstrate efficacy of tissue salvage in a translational preclinical model.