1. Purpose, Core C, the animal model and cell isolation core, provides support for the central animal model used by Projects 1-4. This includes expert surgical instrumentation, follow-up care, and isolation of viable cardiomyocytes from several layers of the left ventricle. Myocytes are employed in projects 1-3 for molecular dissection of potassium and calcium channel physiology in normal and failing hearts. Myocytes are utilized in Project 4 for the purpose of studying neurohormonal modulation of ion channels in normal and failing hearts, and test the role of an altered extracellular matrix environment. Chunk tissues are also provided by Core C at time of animal sacrifice and are used for a variety of molecular assays and histochemical analyses. Two models are employed in Core C, the standard 4 week tachycardia-pacing model of dilated cardiomyopathy, and an accelerated model employing combined neurohumoral activation with relatively short-term tachycardia pacing (Project 4). The major roles of the core are 1) to provide a weekly supply of acutely isolated myocytes from control and abnormal (failing) left ventricles; 2) to provide a standardized hemodynamic/organ electrophysiologic characterization of hearts from which these cells are obtained; 3) to provide chronic surgery-instrumentation and post operative care for animals requiring chronic repetitive conscious hemodynamic assessment; and 4) to provide all required medical records for chronic care and animal maintenance, and to administer these protocols following policies set forth by the Animal Care and Use Policies of the Johns Hopkins University pursuant to guidelines established by the National Institute of Health.
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