Myocardial ischemia and reperfusion: A murine model
Myocardial ischemia and reperfusion: A murine model
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DOI：
10.1152/ajpheart.1995.269.6.h2147
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发表时间：
1995-12-01
影响因子：
4.8
通讯作者：
Ballantyne, CM
中科院分区：
文献类型：
--
作者：
Michael, LH;Entman, ML;Ballantyne, CM
正如各种大型动物研究中所指出的，心肌缺血再灌注会促进一系列复杂的炎症反应。随着基因改造小鼠的发展，人们对开发小鼠模型来研究心血管疾病的作用机制产生了浓厚的兴趣。我们开发了一种小鼠模型来研究冠状动脉闭塞和再灌注效应以及急性和长期进行这些研究所需的方法。在小鼠中，我们对左冠状动脉前降支进行永久或30或60分钟的闭塞，然后再灌注，允许血流通过先前闭塞的冠状动脉床。通过目视以及使用多普勒超声和组织病理学技术记录再灌注。使用图像分析软件程序通过伊文思蓝染料和氯化三苯基四唑染色以及计算机化面积测量法评估危险区域（AAR）和梗塞面积（IS）。在 13 只永久闭塞小鼠中，梗死面积占 AAR 的百分比和 IS 占左心室年龄的百分比分别为 68.6 +/- 4.4 和 28.0 +/- 2.8%。与永久闭塞相比，闭塞 60 分钟和 30 分钟后的再灌注导致 IS 占 AAR 的百分比显着下降。缺血和再灌注心肌的组织学检查显示白细胞浸润到缺血区域以及通常与再灌注相关的收缩带。这种新模型可以评估小鼠的 AAR、IS、心脏功能和病理生理学。利用当前技术开发转基因小鼠以过度表达或靶向突变各种基因，该模型用于了解缺血和再灌注损伤的复杂病理生理学。
Myocardial ischemia followed by reperfusion promotes a complex series of inflammatory reactions as noted in a variety of large animal studies. With development of genetically altered mice, there is intense interest in developing murine models to study mechanisms operative in cardiovascular disease. We developed a mouse model to study coronary artery occlusion and reperfusion effects and the method required to perform these studies both acutely and chronically. In mice, we applied a left anterior descending coronary artery occlusion either permanently or for 30 or 60 min followed by reperfusion allowing flow through the previously occluded coronary artery bed. Reperfusion was documented visually as well as by using Doppler ultrasound and histopathological techniques. The area at risk (AAR) and infarct size (IS) were assessed by Evans blue dye and triphenyltetrazolium chloride staining with computerized planimetry using an image analysis software program. The infarct as percentage of AAR and IS as percent age of the left ventricle in 13 mice with permanent occlusion was 68.6 +/- 4.4 and 28.0 +/- 2.8%, respectively. Reperfusion after occlusions of 60 and 30 min resulted in a significant decrease in IS as a percentage of the AAR compared with permanent occlusion. Histological examination of the ischemic and reperfused myocardium shows infiltration of leukocytes into the ischemic region as well as contraction bands classically associated with reperfusion. This new model allows assessment of AAR, IS, cardiac function, and pathophysiology in the mouse. With the current technology to develop genetically altered mice for overexpression or targeted mutations of various genes, this model is used to understand the complex pathophysiology of ischemia and reperfusion injury.