Ventricular Fibrillation and its Alteration by Pacing

描述（由申请人提供）：本提案的目标是回答关于室颤（VF）期间折返的重要问题，这些问题对于改善心脏骤停的治疗至关重要：如何维持折返？疾病或药物如何改变这些机制？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。据报道，在小心脏中，在VF期间最快激活区域（称为优势域）中存在稳定的静止折返回路（称为母转子）。这些发现在更大的心脏中可能不是真的。我们将在猪的较大心脏中进行电标测研究，以检验以下假设：（1）母转子位于左心室后乳头肌的插入处，（2）这种折返的稳定性受药物和心肌梗死的影响。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以下假设：在主导域中或附近起搏（1）将捕获最大体积的心肌，（2）可以停止折返和VF，以及（3）如果在折返发生之前的心律失常的第一个周期内进行，则可以预防VF。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。我们将在接受心脏手术的患者中进行VF期间的心外膜电标测和心外膜MAP记录，并将在临床电生理实验室中从患者的网篮电极记录，以测试以下假设：（1）存在单个优势域，其VF激活速率快于心室的其余部分，（2）传导阻滞更频繁地发生在沿着冠状血管的路径或具有高度空间离散的不应性的区域中，以及（3）心脏疾病和药物改变VF的组织。具体目标4：使用电气和MAP记录确定是否可以在人体VF期间通过起搏夺获部分心肌。我们将测试以下假设：从优势域起搏（1）在VF期间捕获最大量的组织，（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.