MYOCARDIAL-ISCHEMIA AND REPERFUSION - A MURINE MODEL

Myocardial ischemia followed by reperfusion promotes a complex series of inflammatory reactions as noted in a variety of large animal studie s. With development of genetically altered mice, there is intense inte rest in developing murine models to study mechanisms operative in card iovascular disease. We developed a mouse model to study coronary arter y occlusion and reperfusion effects and the method required to perform these studies both acutely and chronically. In mice, we applied a lef t anterior descending coronary artery occlusion either permanently or for 30 or 60 min followed by reperfusion allowing flow through the pre viously occluded coronary artery bed. Reperfusion was documented visua lly as well as by using Doppler ultrasound and histopathological techn iques. The area at risk (AAR) and infarct size (IS) were assessed by E vans blue dye and triphenyltetrazolium chloride staining with computer ized 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%, res pectively. Reperfusion after occlusions of 60 and 30 min resulted in a significant decrease in IS as a percentage of the AAR compared with p ermanent occlusion. Histological examination of the ischemic and reper fused myocardium shows infiltration of leukocytes into the ischemic re gion as well as contraction bands classically associated with reperfus ion. This new model allows assessment of AAR, IS, cardiac function, an d 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 pathophysi ology of ischemia and reperfusion injury.