Animal Model, Tissue/Cell Harvesting, and Phenotyping Core

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Core B continues to serve the role it played in our present PPG, but with the total number of dogs to be studied reduced, and with introduction of a mouse component and incorporation of phenotyping as a general service to the program. Core B provides all animal models to the three Projects, and Core C studies, and provides non-invasive echo-Doppler phenotyping of these models so that molecular and cellular data can be related to intact organ behavior and each model is confirmed to reflect the primary physiology it is designed to do. Mouse phenotyping using echo as well as terminal study pressure-volume loop analysis will also be the responsibility of this Core. Table 1 provides the general interaction of Core B services to the projects and other core. The strength of the interaction is identified qualitatively by the number of + signs. All three of the projects extensively utilize the canine model, with both molecular, cellular and sub-organelle studies described. The mouse model is primary utilized in Project 1, but myocytes and myocardial tissue from the model will be examined for calcium cycling abnormalities in Project 2 and for mitochondrial function and protein modifications in Project 3. This will enable us to test the consistency of primary findings in calcium cycling, electrophysiology, and mitochondrial function changes between DHF and CRT conditions across species. For the canine model, the core provides primary services generating the model, performing necessary procedures - i.e. ablation and pacemaker implantation, and tissue harvesting. For the mouse models, the core will provide overall colony maintenance, genetic monitoring and genotyping as required, and make tissues and cells available to the other Projects. The second major role of the Core also services all Projects, and is to provide phenotyping of each animal to confirm that the model intended by its instrumentation and design indeed resulted in synchronous, dyssynchronous, or resynchronized HF, quantify the magnitude of the effects generated on global and regional chamber function, and assess dysynchrony in these hearts.