SCOR IN SUDDEN CARDIAC DEATH

我们建议更新犹他州大学的猝死专门研究中心。我们的长期目标仍然是研究异常复极和“猝死”之间的关系。这项研究的目的是通过在实验室的基本观察来开发预防猝死的疗法。为了实现这一目标，我们提出了由四个核心实验室支持的六个相互关联的研究项目。有22名调查人员参与其中。室性心律失常的分子遗传学由MT Keating领导。他将确定遗传性长QT综合征（LQT）和特发性心室颤动（IVF）的新突变，这两种疾病都是由复极期间的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了基廷发现的突变和野生型疾病基因的生物物理学研究。复极化的细胞电生理机制，由KW Spitzer领导。本文探讨了复极化相关心律失常的电生理机制，包括细胞间偶联缺陷、细胞内钙离子和钠/钙交换剂的作用。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，如果我们要将以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。由LS绿色领导的项目5，复极测量的预后价值，继续在前一个资助周期发起的临床研究，目的是发现预测急性心肌梗死后随后猝死的复极测量。在其他条件下的复极化相关介导因子也是该SCOR的人类治疗组分。基于基因的药物治疗LQT和IVF的建议。行政、仪器、细胞处理和信号处理核心实验室支持这六个项目。这种多学科研究工作的结构已经得到优化，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.