The Pathophysiology and Therapy of Pulseless Electrical Activity

无脉冲电活动的病理生理学和治疗

• 批准号: 8966043
• 负责人: HENRY R HALPERIN
• 金额: $ 69.87万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-11-10 至 2018-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8966043
• 关键词: Accident and Emergency department; Acute; Air; Animal Model; Area; Biological Preservation; Blood flow; Cannulas; Cardiac; Cardiopulmonary Resuscitation; Catheters; Chest; Chronic; Clinical Sciences; Development; Devices; Disodium Salt Nitroprusside; Electric Countershock; Failure; Functional disorder; Goals; Health; Heart; Heart Arrest; Hospitals; Hypoxia; Ischemia; Lead; Metabolic; Methods; Muscle; Myocardial Contraction; Nose; Outcome; Patients; Pharmaceutical Preparations; Physicians; Problem Solving; Pump; Reperfusion Injury; Reperfusion Therapy; Research; Residual state; Resuscitation; Survival Rate; Survivors; System; Technology; Translational Research; United States; Vasodilator Agents; Ventricular; Ventricular Fibrillation; Ventricular Tachycardia; base; conditioning; design; heart electrical activity; improved; improved outcome; induced hypothermia; insight; natural hypothermia; novel; operation; preconditioning; prevent; response

DESCRIPTION (provided by applicant): There are at least 500,000 victims of cardiac arrest each year in the United States. In the majority of these patients, the initial rhythm is not ventricular fibrillation (VF) or ventricular tachycardia (VT), but is pulseless electrical activity (PEA) or asystole. The survival rates for VT/VF arrests average around 20%. The survival rates for PEA and asystolic arrests are much lower, however, and average only around 5%. There is a critical need, therefore, for improved resuscitation strategies, since each 1% increase in survival rate would result in approximately 5000 additional survivors. This critical need is most apparent with PEA arrests, since little is known about the pathophysiology or the optimal treatment of these arrests, especially when compared to VT/VF arrests. Defibrillation is the definitive treatment for VT/VF arrest, but is not indicated in PEA arrest. We present the novel hypothesis that most PEA arrests are due to failure of ventricular muscle from acute ischemia and/or hypoxia in a substrate where there has been chronic ischemia and/or hypoxia. This contrasts with most VT/VF arrests where acute ischemia causes VT/VF in a healthier substrate. We further hypothesize that this chronic ischemia and/or hypoxia induces preconditioning, which prevents or delays the occurrence of VF, resulting in PEA arrest. We hypothesize, therefore, that therapy for PEA arrests must be directed at reversing this profound ischemia and/or hypoxia, as well as mitigating reperfusion injury. Even though there may be preconditioning, such preconditioning may not be uniform. In addition, the already severe compromise of the metabolic status of the heart would make any degree of reperfusion injury more detrimental in PEA arrests than in VT/VF arrests. Therapy should, therefore, be directed at generating substantial blood flow during resuscitation, including the use of vasodilators, to reverse the profound ischemia that may be present. Methods for augmenting blood flow should include the use of improved external compression devices, which may be particularly useful for treating out-of-hospital arrests; and the use of extracorporeal systems, which may be particularly useful for in-hospital arrests. Controlled reperfusion, including post conditioning, may be necessary at the beginning of reperfusion to reduce reperfusion injury. Additional preservation strategies may also be useful, including intra-arrest hypothermia. Finally, we hypothesize that each of these strategies will have incremental and additive improvement in outcomes from PEA cardiac arrest. The goals of this project are to improve our understanding of the pathophysiology of PEA cardiac arrest, develop improved methods for augmenting blood flow during resuscitation, and also develop synergistic, improved strategies for mitigating the effects of the profound ischemia and/or hypoxia present in PEA arrest. These studies should provide new information and insights about the pathophysiology of PEA cardiac arrests, and may lead to substantial improvements in the now dismal outcomes from PEA cardiac arrests.

描述（由申请人提供）：美国每年至少有 500,000 名心脏骤停受害者。大多数患者的初始心律不是室颤 (VF) 或室性心动过速 (VT)，而是无脉性电活动 (PEA) 或心搏停止。 VT/VF 逮捕的存活率平均约为 20%。然而，PEA 和心脏骤停的存活率要低得多，平均仅为 5% 左右。因此，迫切需要改进复苏策略，因为存活率每提高 1%，就会导致大约 5000 名额外的幸存者。这种迫切的需求在 PEA 逮捕中最为明显，因为人们对这些逮捕的病理生理学或最佳治疗知之甚少，特别是与 VT/VF 逮捕相比。除颤是 VT/VF 骤停的最终治疗方法，但在 PEA 骤停中并不适用。我们提出了一个新的假设，即大多数 PEA 停搏是由于在存在慢性缺血和/或缺氧的基质中因急性缺血和/或缺氧而导致心室肌衰竭。这与大多数 VT/VF 骤停形成鲜明对比，在大多数 VT/VF 骤停中，急性缺血会在更健康的基质中导致 VT/VF。我们进一步假设这种慢性缺血和/或缺氧会诱导预处理，从而防止或延迟 VF 的发生，从而导致 PEA 停滞。因此，我们假设 PEA 骤停的治疗必须旨在逆转这种严重的缺血和/或缺氧，并减轻再灌注损伤。即使可能存在预处理，但这种预处理可能不均匀。此外，心脏代谢状态已经严重受损，使得任何程度的再灌注损伤在 PEA 骤停中比在 VT/VF 骤停中更加有害。因此，治疗应致力于在复苏期间产生大量血流，包括使用血管扩张剂，以扭转可能存在的严重缺血。增加血流量的方法应包括使用改进的外部加压装置，这对于治疗院外逮捕可能特别有用；以及体外系统的使用，这对于院内逮捕可能特别有用。在再灌注开始时可能需要控制再灌注，包括后处理，以减少再灌注损伤。其他保存策略也可能有用，包括逮捕期间低温。最后，我们假设这些策略中的每一种都会对 PEA 心脏骤停的结果产生增量和附加的改善。该项目的目标是提高我们对 PEA 心脏骤停病理生理学的理解，开发在复苏期间增加血流的改进方法，并开发协同的、改进的策略来减轻 PEA 中存在的严重缺血和/或缺氧的影响逮捕。这些研究应该提供有关 PEA 心脏骤停病理生理学的新信息和见解，并可能使 PEA 心脏骤停目前令人沮丧的结果得到实质性改善。