Core B: Human Cell and Tissue Core

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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.