SCOR IN SUDDEN CARDIAC DEATH

室性心动过速（VT）和纤颤（VF），最常见的 猝死的原因，仍然是一个棘手的健康问题。 的 拟议的SCOR代表了多学科的努力， 临床、整个器官、细胞和计算机建模研究， 了解促进VF和其他室性心律失常的机制， 混沌在这些心律失常中的作用，以及应用的可行性 基于混沌控制理论的心律失常起搏策略。 SCOR将由5个独立项目和3个核心单元组成。 项目1 "人类室性心动过速的交感神经反应"是 主要临床组成部分，并将评估压力感受器的作用- 交感神经活动的介导调节，通过腓神经测量 显微神经造影，作为VT期间血流动力学稳定性的决定因素， VT向VF退化的诱发因素。 混沌理论将 应用于研究交感神经系统的潜在不稳定作用 对心脏功能的影响 项目2 "在大气中的折返波前 心室颤动”将使用高分辨率激动标测， 人和犬的体内心脏，以及犬的体外心室 心外膜切片准备，以描绘电生理 启动和维持VF的机制，特别是 关于促进形成的电生理参数， 多个非平稳的循环波阵面 项目3 "混乱和 心律失常"将与来自项目的实验数据相关联， 2与二维心脏传播的计算机模型， 模拟体外犬制备，以确定是否spatio- 时间混乱在纤颤和其他心室颤动中发挥作用 心律失常，如果是这样，是否可以应用混沌控制策略 治疗上 项目4 '细胞内的机制和后果 心脏钙超载"将探讨潜在的机制异常 在受损心脏代谢过程中的细胞内Ca调节中， 膜片钳和荧光钙指示剂技术是孤立的 心室肌细胞，并将探索条件下，蔡- 在分离的心肌细胞中的超负荷可能导致混乱的心律失常介导 后去极化 项目5 '细胞钾的代谢调节 平衡"将集中在早期细胞钾损失的机制， 缺血和缺氧，一个主要的致瘤因素， 缺血性VF，并将表征ATP敏感性K通道的特性 和跨膜乳酸运动（及其与钾流失的关系）， 分离的肌细胞。 电脑核心A将有助推行 所有项目中使用的计算机模拟， 仪表核心B将为仪表提供支持 开发和维护。 行政核心C将提供 行政支援 项目和核心的共同目标是 提高我们对VF病理生理学的理解，并提供 为新的预防和治疗方法奠定基础。

Ventricular tachycardia (VT) and fibrillation (VF), the most common causes of sudden death, remain an intractable health problem. The proposed SCOR represents a multidisciplinary effort to integrate clinical, whole organ, cellular and computer modelling studies to better understand the mechanisms promoting VF and other ventricular arrhythmias, the role of chaos in these arrhythmias, and the feasibility of applying pacing strategies based on chaos control theory to cardiac arrhythmias. The SCOR will be composed of 5 individual projects and 3 core units. Project 1 "Sympathetic responses in human ventricular tachycardia" is the major clinical component, and will assess the role of baroreceptor- mediated modulation of sympathetic nerve activity, measured by peroneal microneurography, as a determinant of hemodynamic stability during VT and a predisposing factor for degeneration of VT to VF. Chaos theory will be applied to study potentially destabilizing effects of sympathetic nerve activity on cardiac function. Project 2 "Reentrant wavefronts in ventricular fibrillation' will use high resolution activation mapping in the in vivo human and canine heart, and an in vitro canine ventricular epicardial slice preparation to delineate the electrophysiologic mechanisms by which VF is initiated and maintained, particularly with respect to the electrophysiological parameters which promote formation of multiple nonstationary circulating wavefronts. Project 3 'Chaos and cardiac arrhythmias' will correlate the experimental data from Project 2 with computer models of cardiac propagation in two dimensions, simulating the in vitro canine preparation, to determine whether spatio- temporal chaos plays a role in fibrillation and other ventricular arrhythmias, and, if so, whether chaos control strategies can be applied therapeutically. Project 4 'Mechanisms and consequences of intracellular Ca overload in heart' will probe the mechanisms underlying abnormalities in intracellular Ca regulation during impaired cardiac metabolism using patch clamp and fluorescent Ca indicator techniques is isolated ventricular myocytes, and will explore conditions under which Cai- overload in isolated myocytes may lead to chaotic arrhythmias mediated by afterdepolarizations. Project 5 'Metabolic regulation of cellular K balance' will focus on mechanisms of cellular K loss during early ischemia and hypoxia, a major arrhythmogenic factor contributing to ischemic VF, and will characterize properties of ATP-sensitive K channels and transmembrane lactate movement (and its relationship to K loss) in isolated myocytes. Computer Core A will facilitate implementation of computer simulations used in all of the projects, and Biomedical Instrumentation Core B will provide support for instrumentation development and maintenance. Administrative Core C will provide administrative support. The common goal of the projects and cores is to improve our understanding of the pathophysiology of VF, and provide the groundwork for new approaches to its prevention and treatment.