The Pathophysiology and Therapy of Pulseless Electrical Activity

描述(申请人提供)：在美国，每年至少有500,000名心脏骤停患者。在这些患者中，大多数患者的初始节律不是室颤(VF)或室性心动过速(VT)，而是无脉搏电活动 (豌豆)或停搏。VT/VF逮捕的存活率平均在20%左右。然而，PEA和心搏骤停的存活率要低得多，平均只有5%左右。因此，迫切需要改进复苏策略，因为存活率每增加1%，就会增加约5000名幸存者。这种迫切的需要在PEA止血中最为明显，因为人们对这些止血的病理生理学或最佳治疗方法知之甚少，尤其是与VT/VF止血相比。除颤是VT/VF停搏的最终治疗方法，但不适用于PEA停搏。我们提出了一个新的假设，即大多数PEA停搏是由于存在慢性缺血和/或缺氧的基质中的急性缺血和/或缺氧引起的心室肌衰竭所致。这与大多数VT/VF停搏不同，在那里，急性缺血导致VT/VF在更健康的基质中。我们进一步假设，这种慢性缺血和/或低氧可诱导预适应，从而防止或延缓室颤的发生，导致PEA停搏。因此，我们假设，PEA停搏的治疗必须针对逆转这种严重的缺血和/或缺氧，以及减轻再灌注损伤。即使可能存在预适应，这种预适应也可能不是统一的。此外，心脏代谢状态的严重损害将使任何程度的再灌注损伤在PEA停搏中比VT/VF停搏中更有害。因此，治疗应该针对在复苏期间产生大量血流量，包括使用血管扩张剂，以逆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按压装置，这可能对治疗院外止血特别有用；以及使用体外系统，这可能对院内止血特别有用。控制再灌注，包括后处理，在再灌流开始时可能是必要的，以减少再灌流损伤。其他的保存策略也可能是有用的，包括心内低温。最后，我们假设这些策略中的每一种都将对PEA心脏骤停的结果有递增和相加的改善。该项目的目标是提高我们对PEA心脏骤停的病理生理学的了解，开发在复苏过程中增加血流量的改进方法，并开发协同的、改进的策略来减轻PEA骤停中存在的深度缺血和/或缺氧的影响。这些研究应该为PEA心脏骤停的病理生理学提供新的信息和见解，并可能导致PEA心脏骤停目前令人沮丧的结果的实质性改善。

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.