SCOR IN SUDDEN CARDIAC DEATH

我们建议更新犹他大学猝死研究专业中心。我们的长期目标仍然是研究异常复极与“心律失常死亡”之间的关系。这项研究的目标是通过在实验台上的基本观察来开发预防猝死的治疗方法。为了达到这个目标，我们提出了六个相互关联的研究项目，由四个核心实验室支持。涉及22名调查人员。室性心律失常的分子遗传学由MT Keating领导。他将发现遗传性长QT综合征（LQT）和特发性心室颤动（IVF）的新突变，这两种疾病都是由离子通道功能障碍引起的。MC Sanguinetti和MF Sheet在LQT和IVF的分子生理学中提出对Keating发现的突变型和野生型疾病基因进行生物物理研究。重极化的细胞电生理机制，由KW Spitzer领导。本研究探讨了复极相关心律失常的电生理机制，包括细胞间偶联缺陷、细胞内钙和钠/钙交换器的作用。项目4，由RL Lux领导的复极测量，提供了精确测量心脏复极和人类恢复均匀性的新方法，如果我们要将先前项目中的基础科学观察与项目的人体试验联系起来，这是必不可少的。项目5，复极测量的预后价值，由LS Green领导，继续在上一个资助周期启动的临床研究，目标是发现复极测量预测急性心肌梗死后随后的猝死。在其他情况下，复极相关的预后因子也是该SCOR的人类治疗组成部分。提出了基于基因的药物治疗LQT和IVF。管理、仪器、细胞处理和信号处理核心实验室支持这六个项目。这种多学科研究的结构已经得到优化，可以从疾病基因发现中开发知识，并迅速将其转化为预防猝死。

We propose renewal of the Specialized Center of Research in Sudden Death at the University of Utah. Our long-term objective continues to be an investigation of the relationship between abnormal repolarization and ` arrhythmic death. The goal of this investigation is development of therapies that prevent sudden death through fundamental observations at the bench. To achieve this goal we propose six inter-related research projects supported by four core laboratories. Twenty-two investigators are involved. Molecular Genetics of Ventricular Arrhythmias is led by MT Keating. He will identify new mutations underlying the hereditary long QT syndrome (LQT) and idiopathic ventricular fibrillation (IVF), both of which are caused by ion channel dysfunction during repolarization. MC Sanguinetti and MF Sheet, in Molecular Physiology of LQT and IVF, propose biophysical studies of the mutant and wild type disease genes discovered by Keating. Cellular electrophysiological mechanisms of Repolarization, is headed by KW Spitzer. This explores electrophysiological mechanisms of repolarization-related arryhthmias, including contributions by intercellular coupling defects, intracellular calcium and the sodium/calcium exchanger. Project 4, Measurement of Repolarization led by RL Lux, provides new methods for precise measurement of cardiac repolarization and in homogeneities of recovery in humans which are essential if we are to link the basic science observations in the previous Projects with the human trials of Projects. Project 5, Prognostic Value of Repolarization Measures, headed by LS Green, continues a clinical study initiated in the previous grant cycle with the goal of discovery measures of repolarization that predict subsequent sudden death after acute myocardial infarction. Repolarization-related prognosticators in other conditions are also human treatment component of this SCOR. Gene- based pharmacologic therapies of LQT and IVF are proposed. Administration, Instrumentation, Cell Processing and Signal Processing Core laboratories support the six projects. The structure of this multi-disciplinary research effort has been optimized to develop knowledge from disease gene discoveries and rapidly translate it to prevention of sudden death.