The Core will manage animals (rabbits and mice) from which myocytes will be isolated at Loyola for use in all 4 of the projects. The mice used will include wild type and genetically modified mice that are developed and bred in Core D at UCSD (including some that will be subjected to transverse aortic banding to induce chronic pressure overload in Project by Brown). The rabbits used will include both control and heart failure (HF) rabbits (induced by combined pressure and volume overload). The core will also be responsible for the preparation and functional monitoring of HF rabbits during the evolution of dysfunction (under the direction of Dr. S.M. Pogwizd at UIC). The core will also culture adult cardiac myocytes for 24-48 hours for studies involving adenoviral gene transfer. These myocytes will be used directly by the three Loyola projects (l-lll) for functional, imaging and biochemical analysis and also by Project by Brown for biochemical analysis (after experimental treatment by the investigators at Loyola and shipment to UCSD). The procedures carried out are specialized, but the personnel involved are expert in their respective roles and this should run smoothly and efficiently in making the best use of the myocytes available. Mice are especially valuable because of the opportunity to genetically manipulate the molecules under investigation (and we are taking advantage of that in The Genetic Mouse Models and Adenoviruses Core) and collectively we have extensive experience with mouse myocytes and cardiovascular disease models. The mouse work will be complemented by studies in rabbit, where similar genetic manipulation is not practical, but rabbits are highly advantageous here for two major reasons. First, the electrophysiological and Ca handling properties in rabbit ventricle are very similar to that in human. Second, we have already developed a well-characterized rabbit model of heart failure. Indeed, the HF rabbits manifest both severely depressed LV contractile function and spontaneously-occurring ventricular arrhythmias. Rabbit myocytes are also well suited for the measurements to be made (including: voltage clamp, fluorescence imaging, biochemical and molecular studies, and in vitro adenoviral gene transfer. The services provided by this core are essential to the successful completion of the science in Projects by Bers, Blatter, Mignery, and Brown, enabling the elucidation of mechanistic roles of IP3R and CaMKII in ECC, arrhythmogenesis, hypertrophy and HF.
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