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。在这些患者的大多数中，初始节奏不是心室纤颤（VF）或心室心动过速（VT），而是无脉冲的电活动 （豌豆）或助长。 VT/VF逮捕的生存率平均约20％。然而，豌豆和体面逮捕的生存率要低得多，平均仅约5％。因此，迫切需要改善复苏策略，因为生存率每增加1％的生存率将导致大约5000名其他幸存者。豌豆逮捕最明显的是，这种关键需求最为明显，因为对这些逮捕的病理生理学或最佳治疗知之甚少，尤其是与VT/VF逮捕相比。除颤是对VT/VF停滞的确切治疗方法，但在PEA逮捕中没有指示。我们提出了一个新的假设，即大多数豌豆逮捕是由于急性缺血和/或缺氧在患有慢性缺血和/或缺氧的底物中失败。这与大多数VT/VF逮捕形成鲜明对比，急性缺血在更健康的底物中引起VT/VF。我们进一步假设这种慢性缺血和/或缺氧会引起预处理，从而阻止或延迟VF的发生，从而导致PEA停滞。因此，我们假设必须将pea毒治疗疗法用于逆转这种深刻的缺血和/或缺氧，以及减轻再灌注损伤。即使可能存在预处理，这种预处理可能并不统一。此外，已经严重的心脏代谢状况妥协将使任何程度的再灌注损伤在豌豆逮捕中比在VT/VF逮捕中更有损害。因此，应在复苏期间（包括使用血管扩张剂）来扭转可能存在的深刻缺血时，应致力于产生大量的血流。增加血流的方法应包括使用改进的外部压缩装置，这对于治疗院外逮捕特别有用；以及使用体外系统，这可能对于院内逮捕特别有用。在再灌注开始时，可​​能需要受控再灌注，包括后置调节，以减少再灌注损伤。其他保存策略也可能有用，包括逮捕内部体温过低。最后，我们假设这些策略中的每一种都将在豌豆心脏骤停的结果中取得渐进和添加剂的改善。该项目的目标是提高我们对豌豆心脏骤停的病理生理学的理解，开发改进复苏期间血液流动的方法，并制定协同的，改进的策略，以减轻豌豆中存在的深刻缺血和/或缺氧的影响。这些研究应提供有关豌豆心脏骤停的病理生理学的新信息和见解，并可能导致豌豆心脏骤停的惨淡结局得到显着改善。