Core

动物中心将提供最先进的心肌缺血-再灌注损伤模型， 老鼠.在麻醉开胸动物中通过冠状动脉闭塞产生心肌梗死， 随后在急性或存活模型中再灌注不同的时间。在一些实验中， 将接受开胸手术，在冠状动脉周围植入结扎线，并将结扎线外置 以允许1-2周后冠状动脉的闭胸闭塞-再灌注。左室功能 将通过系列超声心动图测量，并在此时进行详细的压力-容积环研究 牺牲将通过四唑染色测量心肌梗死面积，然后进行数码照相， 和定量图像分析。心肌组织样本将与 病理学核心这些模型将用于项目1、3、4和5，以评估某些 缺血-再灌注心肌损伤程度的调节过程，以及缺氧的作用 诱导因子-1（HIF 1）介导的干细胞心脏修复，通过比较野生型对照小鼠与 转基因或经激素处理的小鼠。 Animal Core还将在大鼠提睾肌中提供微血管缺血-再灌注模型 或小鼠，使用视频显微镜定量白细胞滚动，粘附，并在 微循环这些实验将在佩鲁贾的朱塞佩·安布罗西奥博士的实验室进行， 意大利。该模型将应用于转染诱饵寡核苷酸或干扰RNA的大鼠，以抑制 特定的信号通路，并在小鼠与选定的基因突变。该模型将用于项目1， 2、3和5。

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.