Wu Yewen, Yin Xing, Wijaya Cori, Huang Ming-He, McConnell Bradley K
Department of Internal Medicine, Division of Cardiology, University of Texas Medical Branch, USA.
J Vis Exp. 2011 Feb 16(48):2464. doi: 10.3791/2464.
With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular diseases. Animal models that mimic human cardiac disease, such as myocardial infarction (MI) and ischemia-reperfusion (IR) that induces heart failure as well as pressure-overload (transverse aortic constriction) that induces cardiac hypertrophy and heart failure (Goldman and Tarnavski), are useful models to study cardiovascular disease. In particular, myocardial ischemia (MI) is a leading cause for cardiovascular morbidity and mortality despite controlling certain risk factors such as arteriosclerosis and treatments via surgical intervention (Thygesen). Furthermore, an acute loss of the myocardium following myocardial ischemia (MI) results in increased loading conditions that induces ventricular remodeling of the infarcted border zone and the remote non-infarcted myocardium. Myocyte apoptosis, necrosis and the resultant increased hemodynamic load activate multiple biochemical intracellular signaling that initiates LV dilatation, hypertrophy, ventricular shape distortion, and collagen scar formation. This pathological remodeling and failure to normalize the increased wall stresses results in progressive dilatation, recruitment of the border zone myocardium into the scar, and eventually deterioration in myocardial contractile function (i.e. heart failure). The progression of LV dysfunction and heart failure in rats is similar to that observed in patients who sustain a large myocardial infarction, survive and subsequently develops heart failure (Goldman). The acute myocardial infarction (AMI) model in rats has been used to mimic human cardiovascular disease; specifically used to study cardiac signaling mechanisms associated with heart failure as well as to assess the contribution of therapeutic strategies for the treatment of heart failure. The method described in this report is the rat model of acute myocardial infarction (AMI). This model is also referred to as an acute ischemic cardiomyopathy or ischemia followed by reperfusion (IR); which is induced by an acute 30-minute period of ischemia by ligation of the left anterior descending artery (LAD) followed by reperfusion of the tissue by releasing the LAD ligation (Vasilyev and McConnell). This protocol will focus on assessment of the infarct size and the area-at-risk (AAR) by Evan's blue dye and triphenyl tetrazolium chloride (TTC) following 4-hours of reperfusion; additional comments toward the evaluation of cardiac function and remodeling by modifying the duration of reperfusion, is also presented. Overall, this AMI rat animal model is useful for studying the consequence of a myocardial infarction on cardiac pathophysiological and physiological function.
在美国，心力衰竭是导致死亡的主要原因（亨特），生物医学研究对于推进心血管疾病的医学治疗至关重要。模拟人类心脏病的动物模型，如诱发心力衰竭的心肌梗死（MI）和缺血再灌注（IR），以及诱发心脏肥大和心力衰竭的压力超负荷（主动脉弓横断缩窄）（戈德曼和塔尔纳夫斯基），是研究心血管疾病的有用模型。特别是，尽管控制了某些风险因素，如动脉硬化，并通过手术干预进行治疗（蒂格森），心肌缺血（MI）仍是心血管发病和死亡的主要原因。此外，心肌缺血（MI）后心肌的急性丧失会导致负荷条件增加，从而诱发梗死边缘区和远处未梗死心肌的心室重塑。心肌细胞凋亡、坏死以及由此增加的血流动力学负荷会激活多种细胞内生化信号传导，引发左心室扩张、肥大、心室形状变形和胶原瘢痕形成。这种病理重塑以及未能使增加的壁应力恢复正常，会导致进行性扩张，梗死边缘区心肌被纳入瘢痕组织，最终心肌收缩功能恶化（即心力衰竭）。大鼠左心室功能障碍和心力衰竭的进展与大面积心肌梗死患者存活并随后发生心力衰竭的情况相似（戈德曼）。大鼠急性心肌梗死（AMI）模型已被用于模拟人类心血管疾病；特别用于研究与心力衰竭相关的心脏信号传导机制，以及评估治疗策略对心力衰竭治疗的贡献。本报告中描述的方法是大鼠急性心肌梗死（AMI）模型。该模型也被称为急性缺血性心肌病或缺血再灌注（IR）；它是通过结扎左冠状动脉前降支（LAD）急性缺血30分钟，然后松开LAD结扎使组织再灌注来诱导的（瓦西里耶夫和麦康奈尔）。本方案将重点关注再灌注4小时后通过伊文思蓝染料和氯化三苯基四氮唑（TTC）评估梗死面积和危险区域（AAR）；还介绍了通过改变再灌注持续时间对心脏功能和重塑评估的其他评论。总体而言，这种AMI大鼠动物模型对于研究心肌梗死对心脏病理生理和生理功能的影响很有用。
