Reperfusion Injury Protection During Cardiac Arrest: A Novel CPR Method

心脏骤停期间的再灌注损伤保护：一种新型心肺复苏方法

• 批准号: 8394471
• 负责人: Keith Lurie
• 金额: $ 37.05万
• 依托单位: RESQSYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2015-06-13
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8394471
• 关键词: American; Animal Model; Animals; Applications Grants; Basic Life Support; Blood Circulation; Blood Vessels; Blood flow; Brain; Cardiac; Cardiopulmonary Resuscitation; Caring; Cause of Death; Cerebrovascular Circulation; Cerebrum; Chest; Clinical; Clinical Trials; Combined Modality Therapy; Complex; Computer software; Development; Devices; Disease; Electric Countershock; Emergency Situation; Employee Strikes; Environmental air flow; Epinephrine; Event; Family suidae; Feedback; Foundations; Funding; Goals; Heart; Heart Arrest; Home environment; Hospitals; Hour; Human Resources; Infarction; Intracranial Pressure; Ischemia; Life; Manuals; Medical; Metabolic; Methods; Modeling; Morbidity - disease rate; Multi-Institutional Clinical Trial; Myocardial Infarction; Nervous System Physiology; Neurological outcome; Organ; Outcome; Patients; Phase; Physiological; Physiology; Prevention; Process; Provider; Recovery; Relative (related person); Reperfusion Injury; Reperfusion Therapy; Research; Resistance; Resuscitation; Scientific Advances and Accomplishments; Simulate; Small Business Innovation Research Grant; Stroke; Survival Rate; Survivors; System; Technology; Time; Translating; United States; United States National Institutes of Health; Ventricular Fibrillation; Work; base; design; electric impedance; heart function; heart rhythm; hemodynamics; improved; mortality; novel; novel strategies; phase 1 study; pre-clinical; pressure; prevent; programs; prototype; sound; sudden cardiac death; tool

DESCRIPTION (provided by applicant): On average, >90% of patients who suffer from a cardiac arrest die. Nearly all die unexpectedly from this leading cause of death, in part, because the essential components of standard CPR (S-CPR): manual chest compressions at a rate of 100/min, 1 to 1.5 inches in depth and positive pressure ventilations, are an inherently inefficient process, providing less than 25% of normal blood flow to the heart and brain. Despite intensive research, little or no improvement in outcomes has been observed for over half a century. This application builds upon our new understanding of ways to optimize blood flow to the heart and brain during CPR and protect these organs from reperfusion injury. It promises to provide new hope for patients who suffer from sudden cardiac death. The proposed research is focused on demonstrating proof of concept that reducing or preventing reperfusion injury by ischemic postconditioning (PC) is both feasible and critical to markedly enhancing survival with favorable neurological function after cardiac arrest. Building upon recent and significant advances in the treatment of cerebral and cardiac ischemia, where controlled reperfusion has been shown to strikingly reduce stroke and infarct size in patients with cerebral vascular events and myocardial infarction, we have recently temporarily restricted blood flow during the first three minutes of CPR in a pig model of prolonged untreated cardiac arrest. The results have been striking: after 15 minutes of untreated ventricular fibrillation, performing CPR with a number of defined and controlled pauses during the first three minutes of circulation in conjunction with a means to optimize blood flow to the heart and brain during CPR has normalized brain and heart function < 24-hours after arrest. These exciting observations contradict what was previously thought impossible; to restore full life in the setting of prolonged absence of flow and severe metabolic derangement. While antithetical to current practice, this novel approach that significantly reduces and in some cases prevents reperfusion injury may result in a novel and clinically important method of CPR that is easy to implement by EMS personnel and in the home. It provides the promise, based upon sound physiological principles and concepts, to markedly improve neurologically intact survival in patients that have heretofore never been possible to resuscitate. In this application we propose to further explore these findings. In the current application we propose to a) verify that the anticipated improvement in circulation and resuscitation rates can be translated into neurologically intact survival in animal models of cardiac arrest, and b) design and prototype a tool to help perform CPR with PC. If successful, this therapy will result in saving >10,000 more Americans each year from out of hospital cardiac arrest and a similar number of in-hospital survivors based upon the superior blood flow and the ability afforded by PC to protect the brain and heart from reperfusion injury during CPR. PUBLIC HEALTH RELEVANCE: Based upon a combination of multiple newly discovered mechanisms to enhance circulation during CPR, in the current application we propose to a) verify that after prolonged untreated cardiac arrest, controlled re-introduction of blood flow with postconditioning (controlled CPR pauses) combined with a superior hemodynamic method of CPR can be translated into higher rates of neurologically intact survival in animal models of cardiac arrest, and b) develop a CPR device that provides continuous user feedback on quality of CPR and guides the user to perform a novel type of CPR which is key to improving brain and heart blood flow during cardiac arrest with the goal of improving neurologically intact survival. This technology is needed because high quality STD CPR provides less than 20% of normal blood flow to the heart and little more to the brain. Even in the most efficient emergency medical systems, less than 20% of all patients with an out-of-hospital cardiac arrest are discharged from the hospital with intact neurological function. Strikingly, the average national survival to hospitl discharge after out-of-hospital cardiac arrest has remained less than 5% for decades. This complex disease state remains the nation's #1 killer, claiming more than 1000 lives outside the hospital and 1000 lives inside the hospital each day in the United States alone. Improved circulation to the brain and other vital organs during CPR, especially when combined in an overall systems-based approach to pre and post-resuscitation care, has the potential to significantly reduce morbidity and mortality from cardiac arrest.

描述（由申请人提供）：平均而言，>90% 的心脏骤停患者会死亡。几乎所有人都因这一主要原因而意外死亡，部分原因在于标准心肺复苏 (S-CPR) 的基本组成部分：以 100 次/分钟的速度、深度为 1 至 1.5 英寸的手动胸外按压以及正压通气，本质上是低效率的 过程中，向心脏和大脑提供的血流量低于正常血流量的 25%。尽管进行了深入的研究，但半个多世纪以来，观察到的结果很少或根本没有改善。该应用建立在我们对心肺复苏期间优化心脏和大脑血流并保护这些器官免受再灌注损伤的方法的新理解之上。它有望为心源性猝死的患者带来新的希望。拟议的研究重点是证明概念证明，即通过缺血后处理（PC）减少或预防再灌注损伤对于显着提高心脏骤停后的生存率和良好的神经功能来说既可行又至关重要。基于最近在脑和心脏缺血治疗方面取得的重大进展，控制再灌注已被证明可以显着减少脑血管事件和心肌梗塞患者的中风和梗塞范围，我们最近在前三分钟内暂时限制了血流在长期未经治疗的心脏骤停的猪模型中进行心肺复苏。结果令人震惊：未经治疗的心室颤动 15 分钟后，在循环的前三分钟内进行多次定义和受控暂停的心肺复苏，并结合心肺复苏过程中优化流向心脏和大脑的血流的方法，使大脑正常化心脏功能< 24 小时后逮捕。这些令人兴奋的观察结果与以前认为不可能的事情相矛盾。在长期缺乏血流和严重代谢紊乱的情况下恢复完整的生命。虽然与当前的实践相反，这种显着减少甚至在某些情况下预防再灌注损伤的新方法可能会产生一种新颖且具有临床意义的心肺复苏方法，该方法易于由 EMS 人员和在家中实施。它基于合理的生理学原理和概念，有望显着提高迄今为止从未可能复苏的患者的神经完整存活率。在此应用中，我们建议进一步探索这些发现。在当前的应用中，我们建议 a) 验证循环和复苏率的预期改善可以转化为心脏骤停动物模型中神经系统完整的存活率，b) 设计和原型设计一个工具来帮助使用 PC 进行心肺复苏。如果成功，基于优质的血流和 PC 保护大脑和心脏免于再灌注的能力，这种疗法每年将挽救超过 10,000 名院外心脏骤停的美国人，并拯救类似数量的院内幸存者心肺复苏期间受伤。 公共健康相关性：基于多种新发现的增强心肺复苏期间循环的机制的组合，在当前的应用中，我们建议 a) 验证在长时间未经治疗的心脏骤停后，通过以下方式控制血流重新引入： 后处理（受控心肺复苏暂停）与卓越的心肺复苏血流动力学方法相结合，可以转化为心脏骤停动物模型中更高的神经完整存活率，b) 开发一种心肺复苏设备，为用户提供关于心肺复苏质量的持续反馈，并指导用户执行一种新型心肺复苏术，这对于改善心脏骤停期间的大脑和心脏血流至关重要，目的是提高神经系统完整的存活率。之所以需要这项技术，是因为高质量的 STD CPR 提供的心脏血流量不到正常血流量的 20%，而流向大脑的血流量也很少。即使在最高效的紧急医疗系统中，只有不到 20% 的院外心脏骤停患者出院时神经功能完好。引人注目的是，几十年来，全国院外心脏骤停后出院的平均存活率一直低于 5%。这种复杂的疾病状态仍然是美国第一大杀手，仅在美国每天就夺去了医院外 1000 多人的生命和医院内 1000 多人的生命。在心肺复苏期间改善大脑和其他重要器官的循环，特别是与基于整体系统的复苏前和复苏后护理方法相结合，有可能显着降低心脏骤停的发病率和死亡率。

项目成果

Post-conditioning to improve cardiopulmonary resuscitation.

后处理以改善心肺复苏。

• 发表时间: 2014-06
• 作者: Bartos, Jason A;Debaty, Guillaume;Matsuura, Timothy;Yannopoulos, Demetris
• 通讯作者: Yannopoulos, Demetris

Outcomes of intermediate-risk patients treated with transcatheter and surgical aortic valve replacement in the Veterans Affairs Healthcare System: A single center 20-year experience.

退伍军人事务医疗保健系统中接受经导管和外科主动脉瓣置换术治疗的中危患者的结果：单中心 20 年经验。

• 发表时间: 2018
• 作者: Garcia, Santiago;Kelly, Rosemary;Mbai, Mackenzie;Gurevich, Sergey;Oestreich, Brett;Yannopoulos, Demetris;Adabag, Selcuk
• 通讯作者: Adabag, Selcuk

Novelties in pharmacological management of cardiopulmonary resuscitation.

心肺复苏药物管理的新颖性。

• 发表时间: 2013-10
• 作者: Bartos, Jason A;Yannopoulos, Demetris
• 通讯作者: Yannopoulos, Demetris

Enhanced perfusion during advanced life support improves survival with favorable neurologic function in a porcine model of refractory cardiac arrest.

在难治性心脏骤停的猪模型中，高级生命支持期间增强的灌注可提高存活率并具有良好的神经功能。

• 发表时间: 2015-05
• 影响因子: 8.8
• 作者: Debaty, Guillaume;Metzger, Anja;Rees, Jennifer;McKnite, Scott;Puertas, Laura;Yannopoulos, Demetris;Lurie, Keith
• 通讯作者: Lurie, Keith