Mild Hypothermia Catheter for Reperfusion Injury

摘要 ST段心肌梗死（STEMI）是一种严重的急性冠状动脉疾病， 美国人每年都有大量的心肌梗死患者，导致美国医疗保健成本显著增加（急性心肌梗死治疗每年310亿美元）。 STEMI死亡率与心肌损伤程度直接相关，甚至与 在再灌注损伤中，高达50%的总心肌损伤可与直接发生的再灌注损伤（RI）相关 在缺血心肌的血流恢复之后。轻度低温（MH -温度~ 34 ℃）提供心脏保护，并可通过减少心肌代谢需求， 自由基生成、血小板聚集和总梗死面积。然而，MH和所有其他目前的治疗选择， （药理学等）在RI的治疗中基本上不成功。这是因为， 在PCI完成之前，动脉阻塞不允许对感兴趣区域进行治疗， 来不及阻止RI。因此，需要一种创新的经皮方法用于MH输送， 到PCI。选择性自体逆灌流（SARP）是一种新颖有效的经皮治疗MH的方法 PCI之前的输送不需要打开动脉阻塞。MH-SARP用品 将冷却的动脉血通过冠状静脉系统的选定部分逆行灌注到 因此，在PCI之前提供对梗塞区域的治疗以限制RI。逆行灌注 没有MH的情况下，已经进行了大量的研究，但由于需要复杂的设备， 以调节动脉灌注压，避免血管和心肌损伤。我们先前已经表明 冠状静脉系统的部分的选择性插管（即，SARP）可以避免这种可能 损伤并在使用自动灌注的完全动脉闭塞期间提供安全有效的治疗（患者的 自身的动脉压作为驱动力）通过快速连接到由 简单的阀门（不需要复杂的设备）。然而，我们尚未将SARP与 MH降低RI。因此，本I期提案的目的是确认MH-SARP导管， 给予选择性MH治疗并降低心肌梗死猪的RI和梗死面积。基于 我们出色的初步体内结果与SARP单独和我们的实验室测试结果表明，流动 和热交换能力，所提出的系统可以提供临床相关的工具， ST段抬高型心肌梗死患者的RI降低和梗死面积缩小。该项目有能力影响患者， 多种合并症，并覆盖包括NIDDK和NHLBI在内的各个NIH研究所和中心。

ABSTRACT ST segment myocardial infarction (STEMI) is a serious acute coronary condition that affects 500,000 Americans each year and results in significant U.S. healthcare costs ($31B/year for acute MI treatment). STEMI mortality directly relates to the extent of the total myocardial injury and even with the "gold standard" of reperfusion, up to 50% of the total myocardial injury can be related to reperfusion injury (RI) that occurs directly following the restoration of blood flow to the ischemic myocardium. Mild hypothermia (MH - temperature ~ 34¿C) provides cardioprotection and may greatly diminish RI by reducing myocardial metabolic demand, free radical creation, platelet aggregation, and total infarct size. However, MH and all other current therapy options (pharmacologics, etc.) have been largely unsuccessful in the treatment of RI. This is due to the fact that the arterial obstruction does not allow for therapy delivery to the region of interest until PCI is completed, which would be too late to prevent RI. Thus, an innovative, percutaneous approach is needed for MH delivery prior to PCI. Selective auto-retroperfusion (SARP) is a novel and effective percutaneous approach for MH therapy delivery prior to PCI that does not require the opening of the arterial obstruction. MH-SARP supplies retrograde perfusion of cooled arterial blood through selected portions of the coronary venous system to the infarct region of interest, thus providing treatment to the infarct region prior to PCI to limit RI. Retroperfusion without MH has been significantly studied, but largely unadopted because complicated equipment is required to regulate the arterial perfusion pressure to avoid vascular and myocardial injury. We have previously shown that selective cannulation of portions of the coronary venous system (i.e., SARP) can avoid this possible damage and provide safe and effective therapy during a total arterial occlusion using auto-perfusion (patient's own arterial pressure as the driving force) through a quick connection to an arterial source regulated by a simple valve (no need for complicated equipment). However, we have not combined and validated SARP with MH to reduce RI. Thus, the purpose of this Phase I proposal is the validation of a MH-SARP catheter to deliver selective MH treatment and reduce RI and infarct size in swine with myocardial infarction. Based on our excellent preliminary in vivo results with SARP alone and our bench testing results demonstrating the flow and heat exchange capabilities of our catheter, the proposed system may provide a clinically relevant tool for the reduction of RI and infarct size in STEMI patients. This project has the ability to impact patients with multiple comorbidities and reach across various NIH Institutes and Centers including the NIDDK and NHLBI.