Mechanisms for Maintenance of Ventricular Fibrillation

该项目的主要目标是阐明维持室颤(VF)的机制并开发新的治疗方法。最终目标是防止心源性猝死。 具体目的1.猪脑室纤维板中是否存在持续性折返的试验。目前VF研究中最大的争议之一是VF是由少量持续的折返源驱动的，还是由短期波前的持续碎裂驱动的。该项目将在猪的心肌切片上结合心外膜和心内电标测来测试持续折返的存在。 特定目的2.MAP在培养的心肌细胞单层中的繁殖，以测试表面和纤维曲率的影响。在VF过程中，当波前遇到具有不同于其周围环境的性质的区域时，它们会经历局部传播阻塞和碎片。这种异质性通常被认为是由于细胞属性的差异造成的。最近的理论研究表明，即使在均匀的组织中，异质性也可能仅由组织或肌肉纤维的曲率造成。该项目将在培养的心肌细胞单层中测试这些现象的存在。 具体目的3.使用新技术映射和参数化VF模式，测试传播阻塞是由固定的还是动态的非均质性引起的。最近有人提出，VF过程中导致传播阻塞的非均质性是动态的，即由激活/恢复模式引起的，而不是空间上固定的。利用猪心纤颤的全景光学图和新的模式分析算法，该项目将确定室颤期间的传导阻滞是由于静态不均匀、动态不均匀还是这些因素的组合。具体目的4.测试新型模拟控制电路在起搏刺激下捕捉纤颤心肌的能力。先前的研究表明，起搏刺激可以捕捉到纤颤心肌的区域.一类新的模拟电路将被用来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。该项目将开发单部位和多部位起搏电路，并使用分离的灌流猪心的全景光学标测来评估其性能。

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.