1. Core Functions Mouse Physiology and Phenotyping: The small animal physiology core will provide two major services to all four of the projects in this PPG: 1) pathological and physiological models of cardiac hypertrophy and heart failure in mice, and 2) complete and comprehensive phenotyping of wild type and genetically modified mice. Mouse Models systems include: A) Mechanically- induced pressure overload hypertrophy and heart failure using the technique of transverse aortic constriction (TAC), both chronic and intermittent. B) Myocardial Infarction C) Genetic models of heart failure: muscle LIM protein knock out (MLP[-/-]) and calsequestrin (CSQ) overexpression. D) Swimming and running exercise. Mouse Phenotyping will include: A) An in-depth analysis of in vivo cardiac function by serial echocardiography in conscious mice. B) In vivo measurements of intrinsic myocardial contractility by pressure-volume (PV) loop analysis. C) In vivo end-systolic myocardial stress using stress-strain relations. D) In vivo PAR responsiveness by catheter derived hemodynamics. E) Invasive and non-invasive blood pressure recordings and exercise capacity by programmed treadmill testing. F) Ambulatory electrocardiographic telemetry. G) Ex vivo measurements of isolated myocyte contractility. The leaders of this core have been involved in the development of numerous surgical and genetic models of cardiac hypertrophy and heart failure. The Pi's laboratory has considerable expertise in a wide-ranging array of methodologies for the phenotyping of mice. The PI has also been involved in the development of a number of genetic and surgical models of heart failure. For example, microsurgical procedures and hemodynamic evaluation of pressure overload hypertrophy induced through transverse aortic constriction developed by the PI, is now a standard method used by many laboratories around the world.
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