Core

动物核心将提供最先进的完整心肌缺血再灌注损伤模型 老鼠。在麻醉开胸动物中，冠状动脉阻断将造成心肌梗死， 然后在急性模型或存活模型中进行不同时间的再灌注。在一些实验中，小鼠 将接受开胸手术，在冠状动脉周围植入结扎物，并对结扎物进行外部化 以允许1-2周后闭合胸闭塞-再灌注冠状动脉。左心功能 将通过连续超声心动图进行测量，届时将进行详细的压力-容量环研究 牺牲的力量。心肌梗死面积将通过四唑盐染色，然后数字摄影， 和定量的图像分析。心肌组织样本将与组织学合作进行分析 病理核心。项目1、3、4和5将使用这些模型来评估某些 缺血再灌注心肌损伤程度的调控过程及低氧的作用 诱导因子-1(HIF1)介导的干细胞心脏修复，通过比较野生型对照小鼠和 转基因或药物治疗的小鼠。 动物核心还将在大鼠提睾肌中提供微血管缺血-再灌注模型 或小鼠，使用视频显微镜量化白细胞在小鼠体内的滚动、粘连和迁移 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骗寡核苷酸或干扰RNA的大鼠以抑制 特定的信号通路，以及具有选定基因突变的小鼠。该模型将由项目1使用， 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.