MYOCARDIAL PROTECTION OF HASF IN ACUTE MI

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们实验室最近发现了一种新的干细胞旁分泌因子，它是由高表达Akt的间充质干细胞分泌的，可以减少缺氧条件下心肌细胞的凋亡。我们已经建立了一个心脏特异的转基因小鼠系，在心脏α-肌球蛋白重链启动子的控制下过表达这一因子。本研究的具体目的是在野生型和甲型MHC-HASF转基因小鼠中使用Gd超收缩心肌门控磁共振技术评估急性冠脉结扎后24小时的心肌梗死范围和心功能。这将代表一项先导性研究，在该研究中，我们将把我们目前的方法与MRI进行比较，以用于长期、多次扫描(梗死后第14天和第30天)评估这些转基因小鼠的心脏重构。 我们实验室目前用于评估心肌梗死面积的方法依赖于2，3，5-三苯基四氮唑(TTC)和伊文氏蓝染色来描绘危险区域和梗死区。这种方法需要对动物实施安乐死并采集组织。心功能通过超声心动图进行评估。Gd-高对比门控心脏MRI在不需要牺牲动物的情况下，在体内测量梗塞面积方面被证明是准确的。此外，心功能参数，包括射血分数(EF)，舒张末和收缩末期的内径和容量，以及室壁厚度可以被评估。MRI的主要优势是可以在同一动物体内的多个时间点测量心肌梗死面积和心脏重构参数，这减少了动物需要的数量，并提高了收集数据的准确性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our lab has recently identified a novel stem cell paracrine factor secreted by mesenchymal stem cells overexpressing Akt that reduces apoptosis of cardiomyocytes exposed to hypoxia. We have generated a heart specific transgenic mouse line to overexpress this factor under the control of the cardiac alpha-myosin heavy chain promoter. The specific aim of proposed study is to assess myocardial infarct size and cardiac function 24 hours post acute coronary ligation using Gadolinium (Gd) hyperconstrast cardiac gated MRI in wild type and alphaMHC-HASF transgenic mice. This would represent a pilot study in which we would compare our current methodologies to MRI to use in long-term, multiple scan (days 14 and 30 post-infarction) assessment of cardiac remodeling in these transgenic mice. Current modalities utilized by our lab to assess myocardial infarct size are dependent on 2,3,5-triphenyl tetrazolium chloride (TTC) and Evan's Blue staining to delineate the area at risk and infarct area. This method requires euthanizing the animals and harvesting tissue. Cardiac function has been assessed by echocardiogram. Gd-hyperconstrast cardiac gated MRI has been shown to be accurate at measuring in vivo infarct size without the need to sacrifice the animal. In addition, cardiac function parameters including ejection fraction (EF), end-diastolic and end-systolic dimensions and volumes, and wall thickness can be evaluated. The major advantage of MRI allows for infarct area and cardiac remodeling parameters to be measured at multiple time-points in the same animal, which reduces the number of animals need and increase the accuracy of data collected.