Mechanisms for Maintenance of Ventricular Fibrillation

该项目的主要目标是阐明维持心室颤动（VF）的机制，并开发新的治疗方法。最终目的是防止心脏性猝死。 具体目标1。在猪心室板上进行持续折返的试验。目前VF研究中最大的争议之一是VF是由少量持续的重入源驱动的，还是由短寿命波前的持续碎片驱动的。本项目将通过结合猪心肌平板的心外膜和壁内心电标测来测试持续折返的存在。 具体目标2。在培养的肌细胞单层中进行映射传播，以测试表面和纤维曲率的影响。在VF期间，当波前遇到具有与其周围环境不同的属性的区域时，波前经历局部传播块和片段。这种异质性通常被认为是由于细胞特性的差异。最近的理论研究表明，即使在同质组织中，异质性也可能仅仅由组织或肌纤维的弯曲引起。本项目将测试这些现象在单层培养的心肌细胞中的存在 具体目标3。使用新技术映射和参数化VF模式，测试传播阻塞是由于固定还是动态异质性。最近已经提出，在VF期间导致传播阻塞的异质性是动态的，即，由激活/恢复模式诱导，并且不是空间固定的。使用全景光学地图的猪心脏和新的模式分析算法，该项目将确定是否在VF块是由于静态异质性，动态异质性，或这些因素的组合。具体目标4。测试新型模拟控制电路在起搏刺激下捕获舒张心肌的能力。先前的工作已经表明，起搏刺激可以捕获心肌的区域。一种新型的模拟电路将用于控制起搏刺激的传递。最终目标是捕获整个心脏并终止纤颤。本计画将开发单点及多点起搏电路，并利用离体灌注猪心的全景光学标测来评估其效能。

The broad objectives of this project are to elucidate the mechanisms by which ventricular fibrillation (VF) is maintained and to develop novel treatment modalities. The ultimate goal is to prevent sudden cardiac death. Specific Aim 1. Test for the presence of sustained reentry in fibrillating slabs of swine ventricle. One of the largest current controversies in VF research is whether VF is driven by a small number of sustained reentrant sources or by the continual fragmentation of short-lived wavefronts. This project will test for the presence of sustained reentry by combining epicardial and intramural electrical cardiac mapping in slabs of swine myocardium. Specific Aim 2. Map propagation in monolayers of cultured myocytes to test for the effects of surface and fiber curvature. During VF, wavefronts experience local propagation block and fragment when they encounter regions with properties that differ from their surroundings. Such heterogeneity has classically been thought to be due to differences in cellular properties. Recent theoretical work suggests that even in homogeneous tissue, heterogeneity can result solely from the curvature of the tissue or of the muscle fibers. This project will test for the presence of these phenomena in monolayers of cultured myocytes Specific Aim 3. Using novel technology to map and parameterize VF patterns, test whether propagation block is due to fixed or to dynamic heterogeneities. It has recently been proposed that the heterogeneities leading to propagation block during VF are dynamic, i.e., induced by the activation/recovery pattern, and not spatially fixed. Using panoramic optical maps of fibrillating swine hearts and novel pattern analysis algorithms, this project will determine whether block during VF is due to static heterogeneities, dynamic heterogeneities, or a combination of these factors. Specific Aim 4. Test the ability of novel analog control circuits to capture fibrillating myocardium With pacing stimuli. Previous work has shown that pacing stimuli can capture regions of'fibrillating myocardium. A novel class of analog circuits will be used to control the delivery of pacing stimuli. The ultimate goal is to capture the entire heart and terminate fibrillation. This project will develop single anld multisite pacing circuits and evaluate their performance using panoramic optical mapping of isolated perfused swine hearts.