SCOR IN SUDDEN CARDIAC DEATH

此SCOR应用程序的长期目标是调查 心源性猝死的致心律失常机制 冠心病室壁肥厚患者。这些 在30万起突发事件中，绝大多数是由两种疾病造成的 在美国，每年都有心脏死亡。贯穿所有这些主题的统一主题 研究表明，影响心肌结构异常的因素 细胞间通讯导致电生理障碍 对心律失常负责。其中一些反常现象，曾经 已识别、可更正或修改，并可消除或减少 心律失常的频率。此外，认识到这些 动物模型中的异常将导致特异性和 在识别有心脏性猝死风险的患者和 新的治疗干预措施。通过互动和协作 在研究中，我们将追求以下四个主要假设：1) 心肌重构改变心肌细胞的数量、分布或功能 几个重要的心脏结构，包括缝隙连接和 自主神经支配模式，直接和间接的 负责正常的细胞间通讯；2)这些变化 在缝隙连接和神经支配模式不同的不同 并产生不同的电生理模式， 导致不同机制的室性心律失常；3)矫正 这些基因工程细胞的异常将恢复 电生理学走向正常模式，有助于预防发展 室性心律失常；以及4)建立 动物的神经支配和细胞间通讯的异常 模型将为识别和治疗患者提供洞察力 心源性猝死的风险。已经完成了6个项目和2个核心 为实现这些目标而聚集在一起。项目1(Pressler)确定 并尝试修复缝隙连接的异常；项目2(华纳) 识别并尝试修复自主神经支配的改变 和电生理学；项目3(现场)使用心内移植 努力实现心肌再生和长期存活的技术 输送保护心脏的化合物以修复或纠正心脏 潜在的异常；项目4(Hutchins)将动物和 通过提供无创成像模式的临床项目 交感神经和M胆碱能神经支配以及全身心肌 功能；项目5(Mulholland)开发新的PET示踪剂进行研究 心肌和神经的异常；和项目6(Zipes) 与所有项目互动，并调查自主和 冠心病和冠心病患者的电生理模式 心脏肥厚。这些核心包括一个组织病理学核心 (Pressler)，将提供组织组织学资源，以及 负责日常运营的行政核心(Zipes) 司令部。这个SCOR应用程序结合了分子的方法 体外和体内动物的生物学和蛋白质生物化学 电生理学研究，以探索和了解原因 和心律失常导致心源性猝死的机制 病人。

The long term objective of this SCOR application is to investigate the arrhythmogenic mechanisms responsible for sudden cardiac death in patients with coronary heart disease and ventricular hypertrophy. These two disorders are responsible for the vast majority of the 300,000 sudden cardiac deaths annually in the US. The unifying theme through all of the studies is that structural abnormalities of the myocardium that affect cell-to-cell communication lead to electrophysiological disturbances responsible for cardiac arrhythmias. Some of these abnormalities, once identified, can be corrected or modified, with elimination or reduction in the frequency of cardiac arrhythmias. Further, recognition of these abnormalities in animal models will lead to increased specificity and sensitivity in identifying patients at risk for sudden cardiac death and to new therapeutic interventions. Through interactive and collaborative studies, we will pursue the following four major hypotheses: 1) myocardial remodeling alters the number, distribution or function of several important cardiac structures, including gap junctions and autonomic innervation patterns, that are directly and indirectly responsible for normal cell-to-cell communication; 2) these alterations in gap junctions and innervation patterns are different in the various cardiomyopathies and produce different electrophysiological patterns that result in ventricular arrhythmias of different mechanisms; 3) correction of these abnormalities with genetically-engineered cells will restore the electrophysiology toward normal patterns and help prevent the development of ventricular arrhythmias; and 4) establishing the patterns of abnormalities in innervation and cell-to-cell communication in the animal models will provide insight into identifying and treating patients at risk for sudden cardiac death. Six projects and 2 cores have been assembled to address these objectives. Project 1 (Pressler) identifies and attempts to repair abnormalities in gap junctions; Project 2 (Warner) identifies and attempts to repair alterations in autonomic innervation and electrophysiology; Project 3 (Field) uses intracardiac grafting techniques in an effort to effect myocardial regeneration and long term delivery of cardioprotective compounds to repair or correct the underlying abnormalities; Project 4 (Hutchins) bridges the animal and clinical projects by providing noninvasive imaging patterns of sympathetic and muscarinic innervation as well as general myocardial function; Project 5 (Mulholland) develops new PET tracers to study abnormalities of the myocardium and innervation; and Project 6 (Zipes) interacts with all projects and investigates the autonomic and electrophysiologic patterns in a patients with coronary disease and ventricular hypertrophy. The cores include a histopathology core (Pressler) that will provide tissue histology resources, and an administration core (Zipes) responsible for the day-to-day operation of the SCOR. This SCOR application combines the methodologies of molecular biology and protein biochemistry with in vitro and in vivo animal electrophysiology studies in order to explore and understand the causes and mechanisms of arrhythmias responsible for sudden cardiac death in patients.