Defibrillation mechanisms during ischemic arrhythmias

心脏性猝死是美国人死亡的主要原因。为了解决这个问题，人们提出了生存链的概念，以此来描述成功复苏所必需的任务。很明显，院外心脏骤停后早期除颤是提高存活率的关键。1)心律失常的心律失常的成功除颤，2)除颤后心律失常的复发，以及3)除颤后心功能不佳这个项目将解决前两个问题。对急性缺血时自发性心律失常的除颤效果知之甚少。与在非缺血心脏中停止电诱导的室颤相比，需要更大的电击来阻止在急性缺血存在时自发发生的室颤。我们将在四种条件下研究心脏除颤成功和失败后的激活模式，这些条件旨在模拟缺血性室颤的不同方面，在四种条件下电击心脏：(1)急性局部缺血导致自发性室颤，(2)急性局部缺血继而电诱导室颤，(3)急性区域缺血引起自发性室颤，继而导致长时间的全球缺血，(4)急性区域缺血在长时间全脑缺血的情况下引起自发性室颤，以及(4)急性区域缺血在陈旧性心肌梗死的情况下引起自发性室颤。我们将检验这一假设，即在缺血性诱发的自发性心律失常的设置中，除颤电击必须做三件事：(1)停止所有纤颤波前；(2)不重新启动纤颤；(3)停止触发原始心律失常。我们将检验这一假设，即除颤电击是否为自发性心律失常的主要决定因素必须做三件事：(1)停止所有纤颤波前，(2)不重新启动纤颤和(3)停止触发原始的纤颤。我们将检验这一假设，即由急性缺血引起的自发性心律失常能否容易地除颤的主要决定因素取决于心律失常的发生机制和持续时间。我们还将测试这样的假设，即最初的纤颤发作后发生的心律失常是由局灶性机制而不是折返性机制引发的，并且比最初的心律失常更难除颤。为了验证这些假设，我们将通过在冠状动脉中形成血栓来诱导急性缺血，并使用电子标测技术来绘制室性心律失常的起始点，以及除颤休克后最初几次电击后的激活。通过了解除颤电击在这些条件下是如何成功或失败的，我们将更好地开发新的除颤技术，提高心脏性猝死患者的存活率。

Sudden cardiac death is a major cause of mortality in the United States. In an effort to attach this problem, the concept of a Chain of Survival has been presented as a way to characterized the tasks necessary for successful resuscitation. It is clear that early defibrillation is central to improved survival rates following out-of-hospital cardiac arrest. 1) successful defibrillation of the arrhythmia of the arrhythmia, 2) recurrence if arrhythmias following defibrillation, and 3) poor cardiac function following defibrillation This project will address the first two problems. Very little is known about defibrillation efficacy of spontaneous arrhythmias in the presence of acute ischemia. A much larger shock is needed to halt ventricular fibrillation that occurs spontaneously in the presence of acute is ischemia than to halt electrically induced ventricular fibrillation in the non-ischemic heart. We will study the activation patter following successful and failed defibrillation shocks with the heart in four conditions designed to model different aspects of ischemic ventricular fibrillation shocks the heart in four conditions designed to model different aspects of ischemic ventricular fibrillation: (1) acute regional ischemia causing spontaneous ventricular fibrillation, (2) acute regional ischemia followed by electrically induced ventricular fibrillation, (3) acute regional ischemia causing spontaneous ventricular fibrillation which in turn causes prolonged global ischemia, and (4) acute regional ischemia causing spontaneous ventricular fibrillation in the setting of prolonged global ischemia, and (4) acute regional ischemia causing spontaneous ventricular fibrillation in the setting of an old myocardial infarction. We will test the hypothesis that, in the setting of an ischemically induced spontaneous arrhythmia, a defibrillation shock must do three things: (1) stop all fibrillation wavefronts, (2) not restart fibrillation, and (3) stop the trigger of the original arrhythmia. We will test the hypothesis that a major determinant of whether or not a spontaneous arrhythmia, a defibrillation shock must do three things: (1) stop all fibrillation wavefronts, (2)m not restart fibrillation and (3) stop the trigger of the original. We will test the hypothesis that a major determinant f whether or not a spontaneous arrhythmia caused by acute ischemia can be easily defibrillated depends upon the mechanism of initiation of the arrhythmia and duration of the arrhythmia. We will also test the hypothesis that arrhythmias that occur following the initial fibrillation episode are initiated by focal rather than reentrant mechanisms and will be harder to defibrillate than the initial arrhythmia. To test these hypothesis, we will induce acute ischemia by creating a thrombus in a coronary artery and use electrical mapping techniques to map the initiation of ventricular arrhythmias, and the first few post-shock activations following delivery of a defibrillation shock. By developing an understanding of how a defibrillation shock succeeds or fails under these conditions, we will be in a better position to develop new defibrillation techniques that increase survival rates of patients suffering an episode of sudden cardiac death.