Core B - Large Animal Core

摘要 (Core（B） 大型动物模型和电生理核心 在大型哺乳动物中的实验是P01的一个定义性特征。所有这三个项目都需要分析心脏 功能，但住房，手术和分析要求太昂贵， 在单个实验室中进行，通常需要使用专业和复杂的 设备.因此，大型动物中心（中心B）将为所有外科手术提供集中设施 (e.g.,诱导心肌损伤、治疗给药、围手术期护理）、心脏功能 评估（磁共振成像[MRI]、血流动力学）和电生理学评价 （程控电刺激、植入式回路记录器、光学标测）。核心B将位于 伯明翰的亚拉巴马大学的心脏节律管理实验室（CRML），动物将 动物资源计划（Animal Resource Program）。总的来说，这两个设施拥有所有 进行我们提出的实验所需的资源和设备，并配备了一个特殊的 由研究者、心脏外科医生、兽医和技术人员组成的熟练、高效和经验丰富的团队。的 核心B的职责根据以下三个具体目标（SA）进行组织：SA 1， 新生和成年猪的心肌损伤; SA 2，实验治疗的递送（即，移植 工程化人心肌组织补片[hMTP]或最先进的[AAV或modRNA介导的]基因 递送）;和SA 3，电生理和功能评估。核心B也将收集组织， 准备用于组织学和分子分析的生物样品，协调组织的运输， 样品，并确保所有的实验数据，协议，报告和其他文件， 在项目和核心之间安全地存储、存档和共享。值得注意的是，所有的实验程序都将是 严格和一致地定义和执行所有项目，这将加快科学的步伐， 通过使我们能够从整个实验范围的比较中得出有效的结论， 在此PPG下进行。

ABSTRACT (Core B) Large Animal Model and Electrophysiology Core Experiments in large mammals are a defining feature of this P01. All three projects require analyses of cardiac function in neonatal or adult pigs, but the housing, surgical, and analytical requirements are too expensive to be conducted in an individual laboratory and typically require expertise in the use of specialized and sophisticated equipment. Thus, the Large Animal Core (Core B) will provide a centralized facility for all surgical procedures (e.g., induction of myocardial injury, treatment administration, perioperative care), cardiac functional assessments (magnetic resonance imaging [MRI], hemodynamics), and electrophysiological evaluations (programmed electrical stimulation, implanted loop recorders, optical mapping). Core B will be located at the University of Alabama at Birmingham in the Cardiac Rhythm Management Laboratory (CRML), and animals will be housed at the adjacent Animal Resource Program (ARP). Collectively, these two facilities have all of the resources and equipment needed to conduct our proposed experiments and are staffed by an exceptionally skilled, efficient, and experienced team of investigators, cardiac surgeons, veterinarians, and technicians. The responsibilities of Core B are organized under the following three Specific Aims (SAs): SA 1, Induction of myocardial injury in neonatal and adult pigs; SA 2, Delivery of experimental therapy (i.e., transplantation of engineered human myocardial tissue patches [hMTPs] or state-of-the-art [AAV- or modRNA-mediated] gene delivery); and SA 3, Electrophysiological and functional assessments. Core B will also collect tissues, prepare biological samples for histological and molecular analysis, coordinate the shipment of tissues and samples to all Projects, and ensure that all experimental data, protocols, reports, and other documentation are securely stored, archived, and shared among Projects and Cores. Notably, all experimental procedures will be rigorously and consistently defined and executed for all Projects, which will accelerate the pace of scientific discovery by enabling us to draw valid conclusions from comparisons across the full range of experiments conducted under this PPG.