Core B: Human Cell and Tissue Core

核心B：摘要 人体细胞和组织核心(核心B)将为所有3个项目提供可获得的人体心脏组织 和Core C。衰竭的心脏表现为左心室(LV)收缩功能严重受压。 以及自发发生的室性心律失常(这可能导致心源性猝死)，而不是衰竭 心脏有保存的心功能，将作为适当的控制。人体心脏组织的研究 而肌细胞对于验证生理生化的发现是否重要 动物和细胞模型的特性也适用于人类。因此，不合格和不合格的采购 人体心脏组织衰竭将是所有PPG项目的关键。核心B将负责采购 接受临床指征心脏移植的终末期心力衰竭患者的心脏衰竭。 左心室收缩功能正常的无衰竭心脏将从脑死亡的供者那里获得，这些供体 由于技术原因，心脏不适合移植。人体心脏组织的获取和 处理包括快速冷冻和在液氮中储存组织，分离小梁组织和 用于病理分析的人心脏组织的固定和加工。其核心是 还将负责根据HIPAA获取相关的临床和人口统计信息 和IRB法规。所执行的程序是专门的，但涉及的人员都是专家。 因此，组织和肌细胞将得到高效和有效的利用。我们目前的试点数据 证明利用这些组织和细胞获取、分发和获得高质量数据的可行性。 使用来自共同来源的人类心脏组织将允许集成和组合生化， 人体衰竭和非衰竭心脏组织和心肌细胞的蛋白质组学和电生理学评估。 该中心所提供的服务对顺利完成拟议的研究至为重要。 项目1-3阐明肌节调节的收缩功能障碍的机制 心力衰竭的发展。

Core B: Abstract The Human Cell and Tissue Core (Core B) will provide procured viable human heart tissue for all 3 projects and Core C. Failing human hearts manifest both severely depressed left ventricular (LV) contractile function and spontaneously-occurring ventricular arrhythmias (that can lead to sudden cardiac death), while non-failing heart have preserved ventricular function that will serve as a suitable control. Studies in human heart tissue and myocytes are important to validate whether or not the findings of the physiological and biochemical properties from animal and cellular models are also true in humans. Thus, procurement of failing and non- failing human heart tissue will be critical for all of the PPG projects. Core B will be responsible for procuring failing human hearts from subjects with end-stage HF undergoing clinically indicated heart transplantation. Non-failing human hearts with normal LV systolic function will be procured from brain-dead donors whose hearts are not suitable for transplantation due to technical reasons. The human heart tissue procurement and processing includes flash-freezing and storage of tissue in liquid nitrogen, isolation of trabecular tissue and ventricular myocytes, and fixation and processing of human heart tissues for pathological analysis. The core will also be responsible for obtaining relevant clinical and demographic information in compliance with HIPAA and IRB regulations. The procedures carried out are specialized, but the personnel involved are expert in their respective roles and thus the tissue and myocytes will be used efficiently and effectively. Our present pilot data attest to the feasibility of procuring, distributing and obtaining high-quality data with these tissues and cells. The use of human heart tissue from a common source will allow integrated and combined biochemical, proteomic, and electrophysiological assessment of human failing and non-failing heart tissue and myocytes. The services provided by this core are essential to the successful completion of the proposed studies in Projects 1-3 to elucidate the mechanism of sarcomere regulated contractile dysfunction during the development of heart failure.