MECHANISMS FOR MAINTENANCE OF VENTRICULAR FIBRILLATION

描述(改编自申请者的摘要)： 该项目旨在阐明室颤(VF)的发病机制。 维护好了。具体目标1将决定代理如何解开 类似二乙酰单肟(DAM)或细胞松弛素D(Cyto-D)的兴奋-收缩 和/或电压敏感染料影响VF激活模式。的影响 这些机械解偶联药物将通过绘制猪心图进行检查 体表电信号记录：1)原位记录，2)离体心电记录，3) 用解偶联药物隔离灌流的心脏和4)隔离和灌流 心脏含有解偶联药物和电压敏感染料。特定目标2将 VF过程中传播阻断区域与静态和动态的关联 复极化特性。这项研究将确定传播是否受阻于 VF的光学标绘数据与1)色散不均匀的区域相关 固有动作电位时程(Apd)和2)频率依赖的 复极不稳定性导致动作电位时程振荡的幅度越来越大 最终导致VF中的阻塞。具体目标3将决定流行的 VF期间的传播模式及其与阻塞的关系。申请者将会 开发一种方法来记录完整的心外膜激活图，使用2 摄像机，如“全景地图”，将使用新的算法来 明确描述由(1)转子、(2)游荡引起的激活 小波或(3)心外膜突破。数据将区别于 另一种假想的VF机制。该项目将测试与以下相关的假设 对旋翼漂移的阻挡以及壁内再入与 心外膜表面。

DESCRIPTION (Adapted from Applicant's) Abstract): The central goal of the project is to clarify the mechanisms by which ventricular fibrillation (VF) is maintained. Specific Aim 1 will determine how agents that uncouple excitation-contraction like diacetyl monoxime (DAM) or cytochalasin D (cyto-D) and/or the voltage-sensitive dye affect VF activation patterns. The effects of these mechanical uncoupling drugs will be examined by mapping pig hearts with surface electrogram recordings 1) in situ, 2) in isolated perfused hearts, 3) isolated perfused hearts with uncoupling drugs and 4) isolated and perfused hearts with uncoupling drugs and voltage sensitive dyes. Specific Aim 2 will correlate the regions of propagation block during VF with static and dynamic repolarization properties. The study will determine if propagation block in optical mapping data of VF correlate with 1) areas of non-uniform dispersion of intrinsic action potential duration (APD) and 2) if rate-dependent repolarization instabilities cause APD oscillations of growing amplitude that eventually lead to block in VF. Specific Aim 3 will determine the prevalent mode of propagation during VF and its relationship to block. The applicant will develop a method to record a complete epicardial map of activation using 2 cameras as in "Panoramic Mapping" and will use novel algorithms to unambiguously characterize activation arising from (1) rotors, (2) wandering wavelets or (3) epicardial breakthrough. The data will differentiate between alternate hypothesized VF mechanisms. The project will test hypotheses relating block to the drift of rotors and the interaction of intramural reentry with the epicardial surface.