Myocardial ischemia and reperfusion: a murine model

Abstract

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 percentage 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.

Rodent models of heart failure: an updated review

“…This model has confirmed the benefits of reperfusion since infarct size was found to be significantly lower than after permanent occlusion of the coronary artery. However, they also revealed the diversity of results as a consequence of mouse left coronary anatomic high variability [187].…”

Near-Infrared Fluorescent Imaging of Matrix Metalloproteinase Activity After Myocardial Infarction

“…Male C57BL6J mice, ranging in age from 8 to 12 weeks and weighing 25 to 30 g, underwent left anterior descending coronary artery (LAD) ligation to induce MI. 25 Animals were anesthetized intraperitoneally with ketamine 0.065 mg/g body wt, acepromazine 0.001 mg/g, and xylazine 0.013 mg/g. Animals were intubated and ventilated with a rodent respirator.…”

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

“…Evans blue dye (1%) was perfused into the aorta and coronary arteries with distribution throughout the left ventricular wall proximal to the site of coronary artery ligation as described previously [12]. The non-ischemic area was stained blue.…”