Core B - Large Animal Core

摘要

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.