Ventricular Fibrillation and its Alteration by Pacing

描述（由申请人提供）：本提案的目的是回答心室颤动（VF）期间再入的重要问题，这对改善心脏骤停的治疗至关重要：如何维持再入？这些机制是如何被疾病或药物改变的？是否可以通过起搏来阻止或停止VF期间的再入？具体目标1：使用电成像来确定猪体内是否存在母转子。在小心脏中，有一个稳定的、静止的重入电路，称为母转子，被报道在VF期间最快的激活区域，称为主导域。这些发现可能不适用于更大的心脏。我们将在猪的大心脏中进行电图研究，以验证以下假设：(1)母转子位于左室后乳头肌的插入处；(2)该再入的稳定性受到药物和心肌梗死的影响。具体目标2：使用电子和光学映射来优化起搏技术，以阻止或防止VF。我们将使用映射来优化刺激波形和电极，这些波形和电极将用于测试以下假设：在主导域或其附近的起搏(1)将捕获最大容量的心肌，(2)可以阻止再入心性和心室颤动，(3)如果在心律失常再入心性形成之前的第一个周期进行起搏，可以预防心室颤动。具体目标3：利用电图和单相动作电位（MAP）记录来研究人类VF维持的机制。我们将对接受心脏手术的患者进行心外膜电测绘和心外膜MAP记录，并将在临床电生理实验室对患者进行篮状电极记录，以验证以下假设：(1)存在一个单一的主导区域，其VF激活率比心室其他部分快；(2)传导阻滞更常发生在沿冠状血管路径或难阻性空间弥散性高的区域；(3)心脏病和药物改变了VF的组织。具体目标4：使用电和MAP记录来确定是否有可能通过人类心室颤动期间的起搏来捕获一部分心肌。我们将检验以下假设：从优势域起搏(1)捕获VF期间最大数量的组织，(2)停止最有组织的VF类型。

DESCRIPTION (provided by applicant): The goal of this proposal is to answer important questions about reentry during ventricular fibrillation (VF) that are crucial for improving therapy for sudden cardiac arrest: How is reentry maintained? How are these mechanisms altered by disease or drugs? Can reentry during VF be prevented or halted by pacing. Specific Aim 1: Use electrical mapping to determine if a mother rotor exists in swine. In small hearts a stable, stationary reentrant circuit, called the mother rotor, has been reported in the fastest activating region during VF, called the dominant domain. These findings may not be true in larger hearts. We will perform electrical mapping studies in the larger hearts of pigs to test the hypotheses that (1) a mother rotor is located at the insertion of the posterior LV papillary muscle and (2) the stability of this reentry is affected by drugs and myocardial infarction. Specific Aim 2: Use electrical and optical mapping to optimize pacing techniques to halt or prevent VF. We will use mapping to optimize stimulation waveforms and electrodes which will be used to test the hypotheses that pacing in or near the dominant domain (1) will capture the largest volume of myocardium, (2) can halt reentry and VF, and (3) can prevent VF if performed during the first cycles of an arrhythmia before reentry has developed. Specific Aim 3: Use electrical mapping and monophasic action potential (MAP) recordings to investigate the mechanisms of VF maintenance in humans. We will perform electrical epicardial mapping and epicardial MAP recordings during VF in patients undergoing cardiac surgery and will record from basket electrodes in patients in the clinical electrophysiology laboratory to test the hypotheses that (1) there is a single dominant domain with a VF activation rate faster than in the remainder of the ventricles, (2) conduction block occurs more frequently along the paths of coronary vessels or in regions with a high spatial dispersion of refractoriness, and (3) cardiac disease and drugs alter the organization of VF. Specific Aim 4: Use electrical and MAP recordings to determine if it is possible to capture a portion of the myocardium by pacing during VF in humans. We will test the hypotheses that pacing from the dominant domain (1) captures the maximum amount of tissue during VF and (2) halts the most organized types of VF.