Ventricular Fibrillation and its Alteration by Pacing

本提案的目的是回答有关心室颤动（VF）期间折返的重要问题 对于改善心脏骤停的治疗至关重要：如何维持折返？这些是怎么 疾病或药物改变的机制？心室颤动期间的折返是否可以通过起搏来防止或停止。 具体目标1：使用电标测确定猪体内是否存在母转子。在小小的心里 在最快的激活区，已经报道了一个稳定的，静止的重入回路，称为母转子 在VF期间，称为优势域。这些发现在更大的心脏中可能不是真的。我们将执行 在猪的较大心脏中进行电标测研究，以检验以下假设：（1）母转子位于 在左心室后乳头肌的插入处，以及（2）这种折返的稳定性受药物的影响 和心肌梗塞。 具体目标2：使用电气和光学标测优化起搏技术，以停止或预防VF。 我们将使用标测来优化刺激波形和电极，这些波形和电极将用于测试 假设在主导域（1）中或附近起搏将捕获最大体积的心肌， (2)可以停止折返和VF，以及（3）如果在心律失常的第一个周期期间执行，则可以防止VF 在重返大气层之前 具体目标3：使用电标测和单相动作电位（MAP）记录来研究 人类VF维持的机制。我们将进行心外膜电标测， 接受心脏手术的患者VF期间的MAP记录， 患者在临床电生理实验室测试的假设，（1）有一个单一的优势 心室激活速率快于心室其余部分的区域，（2）发生传导阻滞 更频繁地沿着冠状血管的路径或在具有高空间离散度的区域中， 难治性;（3）心脏疾病和药物改变VF的组织。 具体目标4：使用电子和MAP记录来确定是否有可能捕获部分的 心脏起搏在VF在人类。我们将检验从属音开始的步频 域（1）在VF期间捕获最大量的组织，以及（2）停止最有组织的VF类型。

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 myocardialinfarction. 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.