Wilf Family Cardiovascular Research Institute, Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J Histochem Cytochem. 2013 Aug;61(8):555-70. doi: 10.1369/0022155413493912. Epub 2013 May 28.
Mouse models of myocardial infarction are essential tools for the study of cardiac injury, repair, and remodeling. Our current investigation establishes a systematic approach for quantitative evaluation of the inflammatory and reparative response, cardiac function, and geometry in a mouse model of reperfused myocardial infarction. Reperfused mouse infarcts exhibited marked induction of inflammatory cytokines that peaked after 6 hr of reperfusion. In the infarcted heart, scar contraction and chamber dilation continued for at least 28 days after reperfusion; infarct maturation was associated with marked thinning of the scar, accompanied by volume loss and rapid clearance of cellular elements. Echocardiographic measurements of end-diastolic dimensions correlated well with morphometric assessment of dilative remodeling in perfusion-fixed hearts. Hemodynamic monitoring was used to quantitatively assess systolic and diastolic function; the severity of diastolic dysfunction following myocardial infarction correlated with cardiomyocyte hypertrophy and infarct collagen content. Expression of molecular mediators of inflammation and cellular infiltration needs to be investigated during the first 72 hr, whereas assessment of dilative remodeling requires measurement of geometric parameters for at least four weeks after the acute event. Rapid initiation and resolution of the inflammatory response, accelerated scar maturation, and extensive infarct volume loss are important characteristics of infarct healing in mice.
心肌梗死的小鼠模型是研究心脏损伤、修复和重构的重要工具。我们目前的研究建立了一种系统的方法,用于定量评估再灌注心肌梗死小鼠模型中的炎症和修复反应、心功能和几何形状。再灌注后的小鼠梗死区表现出明显的炎症细胞因子诱导,在再灌注 6 小时后达到峰值。在梗死心脏中,疤痕收缩和心室扩张至少持续 28 天;梗死成熟与疤痕明显变薄有关,伴随着体积损失和细胞成分的快速清除。超声心动图测量的舒张末期尺寸与灌注固定心脏的扩张性重构的形态计量评估非常吻合。血流动力学监测用于定量评估收缩和舒张功能;心肌梗死后舒张功能障碍的严重程度与心肌细胞肥大和梗死胶原含量相关。在最初的 72 小时内需要研究炎症和细胞浸润的分子介质表达,而在急性事件后至少四周需要测量几何参数来评估扩张性重构。炎症反应的快速启动和消退、疤痕的快速成熟以及梗死体积的大量损失是小鼠梗死愈合的重要特征。