Core B: Human Cell and Tissue Core

核心B：摘要 人类细胞和组织核心（核心B）将为所有3个项目提供采购的活人类心脏组织 核心C。衰竭的人类心脏表现出严重的左心室（LV）收缩功能抑制， 和自发发生的室性心律失常（可导致心脏性猝死），而非失败 心脏具有保存心室功能，其将用作合适的对照。人体心脏组织研究 和肌细胞是重要的，以验证是否有生理和生化的研究结果， 来自动物和细胞模型的特性在人类中也是真实的。因此，采购失败和不- 失败的人类心脏组织对所有PPG项目都至关重要。核心B将负责采购 来自接受临床指征心脏移植的终末期HF受试者的衰竭人类心脏。 具有正常LV收缩功能的非衰竭人类心脏将从脑死亡供体获得，其 由于技术原因，心脏不适合移植。人类心脏组织的获取和 处理包括快速冷冻和在液氮中储存组织，分离小梁组织， 心室肌细胞，以及用于病理分析的人心脏组织的固定和处理。核心 还将负责根据HIPAA获得相关临床和人口统计信息 IRB法规。所执行的程序是专门的，但所涉人员是他们的专家。 各自的作用，因此组织和肌细胞将被高效和有效地利用。我们目前的试点数据 证明了采购、分发和获得这些组织和细胞的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整合和组合的生物化学， 人衰竭和非衰竭心脏组织和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成功完成拟议的研究至关重要， 项目1-3阐明肌节调节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.