Core

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The Animal Core will provide state-of-the-art models of myocardial ischemia-reperfusion injury in the intact mouse. Myocardial infarction will be created by coronary artery occlusion in the anesthetized open chest animal, followed by reperfusion for various periods of time in either acute or survival models. In some experiments, mice will undergo thoracotomy, implantation of a ligature around a coronary artery, and exteriorization of the ligature to allow for closed chest occlusion-reperfusion of the coronary artery 1-2 weeks later. Left ventricular function will be measured by serial echocardiography and detailed pressure-volume loop studies will be done at the time of sacrifice. Myocardial infarct size will be measured by tetrazolium staining, followed by digital photography, and quantitative image analysis. Myocardial tissue samples will be analyzed histologically in collaboration with the Pathology Core. These models will be used by Projects 1, 3, 4, and 5 to assess the importance of certain regulatory processes on the extent of myocardial injury in ischemia-reperfusion, and on the role of hypoxia inducible factor-1 (HIF1) mediated stem cell cardiac repair, by comparing results in wild type control mice with genetically modified or pharmacologically treated mice. The Animal Core will also provide a microvascular ischemia-reperfusion model in the cremaster muscle of the rat or mouse, using videomicroscopy to quantify leukocyte rolling, adherence, and transmigration in the microcirculation. These experiments will be performed in the laboratory of Dr Giuseppe Ambrosio in Perugia, Italy. The model will be applied to rats transfected with decoy oligonucleotides or interferring RNA to inhibit specific signaling pathways, and in mice with selected genetic mutations. The model will be used by Projects 1, 2, 3, and 5.