Defibrillation mechanisms during ischemic arrhythmias

心脏性猝死是美国死亡的主要原因。为了解决这个问题，提出了生存链的概念，作为成功复苏所需任务的特征。很明显，早期除颤对提高院外心脏骤停后的存活率至关重要。1)心律失常的心律失常成功除颤，2）如果心律失常除颤后复发，3）除颤后心脏功能不良本项目将解决前两个问题。对于急性缺血时自发性心律失常的除颤效果知之甚少。与在非缺血性心脏中停止电诱发的心室纤颤相比，在急性缺血的情况下停止自发发生的心室纤颤需要更大的电击。我们将研究成功和失败的除颤电击后的激活模式，心脏在四种条件下设计用于模拟缺血性室颤的不同方面，电击心脏在四种条件下设计用于模拟缺血性室颤的不同方面：（1）急性局部缺血引起自发性心室颤动，（2）急性局部缺血后电诱发心室颤动，（3）急性局部缺血引起自发性心室纤维性颤动，其又引起长期的全脑缺血，和（4）急性局部缺血引起长期的全脑缺血情况下的自发性心室纤维性颤动，和（4）急性局部缺血引起陈旧性心肌梗塞情况下的自发性心室纤维性颤动。我们将检验以下假设：在缺血诱发的自发性心律失常的情况下，除颤电击必须完成三件事：（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。我们将检验一个假设，即是否是自发性心律失常的一个主要决定因素，除颤电击必须做三件事：（1）停止所有纤颤波阵面，（2）m不重新开始纤颤和（3）停止触发的原始。我们将检验一个假设，即急性缺血引起的自发性心律失常是否容易除颤的主要决定因素取决于心律失常的起始机制和心律失常的持续时间。我们还将检验以下假设：初始房颤发作后发生的心律失常是由局灶性而非折返性机制引发的，并且比初始心律失常更难消除。为了检验这些假设，我们将通过在冠状动脉中形成血栓来诱导急性缺血，并使用电标测技术来标测室性心律失常的起始以及除颤电击后的前几次电击后激活。通过了解除颤电击在这些条件下是如何成功或失败的，我们将能够更好地开发新的除颤技术，提高心脏性猝死患者的生存率。

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.