Attenuating reperfusion injury with combined hypothermia and gradual reperfusion.

通过低温和逐渐再灌注相结合来减轻再灌注损伤。

• 批准号: 8453308
• 负责人: THOMAS L MERRILL
• 金额: $ 29.98万
• 依托单位: FOCALCOOL, LLC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8453308
• 关键词: Acute myocardial infarction; Affect; Angioplasty; Animal Model; Animal Testing; Animals; Area; Attenuated; Biochemical Process; Blood; Blood flow; Canis familiaris; Caring; Catheters; Combined Modality Therapy; Controlled Study; Coronary; Coronary artery; Custom; Devices; Educational workshop; Emergency Situation; Event; Family suidae; Freezing; Goals; Heart; Infarction; Intervention; Ischemia; Joints; Legal patent; Marketing; Mechanics; Modeling; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; National Heart, Lung, and Blood Institute; Organ; Organ Survival; Outcome; Patients; Performance; Perfusion; Phase; Pre-Clinical Model; Primary Health Care; Procedures; Protocols documentation; Ramp; Reperfusion Injury; Reperfusion Therapy; Risk; Safety; System; Techniques; Technology; Temperature; Test Result; Testing; Therapeutic; Time; Tissues; Universities; Work; attack victim; base; blood perfusion; clinically relevant; design; improved; in vivo; innovation; natural hypothermia; percutaneous coronary intervention; pressure; prototype; public health relevance; statistics; technological innovation

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.

描述（由申请人提供）：心脏病发作期间的初级护理目标是快速恢复血液灌注。然而，再灌注虽然能够使器官存活，但却是矛盾的。它还会导致破坏性的生化过程。虽然已经研究了许多急性心肌梗死 (AMI) 的辅助疗法，但仍需要创新的联合疗法。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结合起来，以产生附加的甚至协同的效益，从而改善 AMI 的结果。具体目标：1）开发一种组合治疗装置，可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，并在大型动物转化缺血再灌注模型中提供组织挽救益处。为了实现目标#1，将开发一套固定的设计输入要求和可行性点，将创建五个完全表征和强大的设备原型，为体内测试做好准备，并根据组织冷却能力和潜在功效制定最佳操作方案将选择体内测试。对于目标#2，最佳操作方案将在大型动物缺血再灌注模型中进行测试。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，证明了临床相关组织挽救的潜力。相关性：美国每年约有 110,000 人接受紧急血管成形术。根据美国心脏协会 2010 年统计数据，20% 的首次心脏病发作患者在发病后一年内死亡。 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，从而改善紧急血管成形术患者的预后。如果第一阶段的目标是证明联合技术的安全性、冷却能力和组织挽救可行性成功，第二阶段将冻结 GLP 动物测试和 IDE 应用的设计，并在转化临床前模型中证明组织挽救的功效。