Xu Zhaobin, Alloush Jenna, Beck Eric, Weisleder Noah
Davis Heart & Lung Research Institute, Department of Physiology and Cell Biology, The Ohio State University.
Davis Heart & Lung Research Institute, Department of Physiology and Cell Biology, The Ohio State University;
J Vis Exp. 2014 Apr 10(86):51329. doi: 10.3791/51329.
Acute or chronic myocardial infarction (MI) are cardiovascular events resulting in high morbidity and mortality. Establishing the pathological mechanisms at work during MI and developing effective therapeutic approaches requires methodology to reproducibly simulate the clinical incidence and reflect the pathophysiological changes associated with MI. Here, we describe a surgical method to induce MI in mouse models that can be used for short-term ischemia-reperfusion (I/R) injury as well as permanent ligation. The major advantage of this method is to facilitate location of the left anterior descending artery (LAD) to allow for accurate ligation of this artery to induce ischemia in the left ventricle of the mouse heart. Accurate positioning of the ligature on the LAD increases reproducibility of infarct size and thus produces more reliable results. Greater precision in placement of the ligature will improve the standard surgical approaches to simulate MI in mice, thus reducing the number of experimental animals necessary for statistically relevant studies and improving our understanding of the mechanisms producing cardiac dysfunction following MI. This mouse model of MI is also useful for the preclinical testing of treatments targeting myocardial damage following MI.
急性或慢性心肌梗死(MI)是导致高发病率和死亡率的心血管事件。要确定心肌梗死期间起作用的病理机制并开发有效的治疗方法,需要能够可重复模拟临床发病情况并反映与心肌梗死相关的病理生理变化的方法。在此,我们描述一种在小鼠模型中诱导心肌梗死的手术方法,该方法可用于短期缺血再灌注(I/R)损伤以及永久性结扎。该方法的主要优点是便于定位左冠状动脉前降支(LAD),从而能够准确结扎该动脉,诱导小鼠心脏左心室缺血。结扎线在LAD上的精确定位提高了梗死面积的可重复性,从而产生更可靠的结果。结扎线放置的更高精度将改善模拟小鼠心肌梗死的标准手术方法,从而减少统计相关研究所需的实验动物数量,并增进我们对心肌梗死后导致心脏功能障碍机制的理解。这种心肌梗死小鼠模型也可用于针对心肌梗死后心肌损伤治疗的临床前测试。