Core B will be responsible for providing porcine models of myocardial infarction to each of the 3 projects in this PPG. Core Functions: A. To generate a pig Ml model with cardiac structural and functional derangements for all projects. B. To measure changes in cardiac structure and function after Ml. C. To treat Ml pigs (with AAV or drugs) and insert BrdU-containing minipumps as described in each of the projects, and measure the effects on cardiac structure and function. D. To provide the 3 projects with fixed tissue, isolated myocytes and frozen tissue for project specific experiments. Each of the three projects within this PPG will explore fundamental aspects of cardiac dysfunction induced by myocardial infarction in pigs. This animal model will be used because it has critical physiological features that mimic human biology. In addition, the Ml model to be used induces changes in cardiac structure and function that approximate conditions in humans with ischemic heart disease. Core B will supply investigators with a reliable, well characterized animal model so that each project can explore the mechanism they think is critical to heart failure induction and progression. Core B will also treat animals with agents that each of the 3 projects think will blunt or reverse the pathological consequences of Ml. At the completion of each study, Core B will prepare pig heart tissue (and blood) for histology, molecular biology and cell function analysis.
This Core will establish a large animal model of cardiac dysfunction, for testing of novel therapies for ischemic heart disease. This animal model has characteristics that are similar to humans. These features of the model system should allow our results to be translated into novel therapies for patients who have had a myocardial infarction and have a poor prognosis.
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