Kim Dae-Hee, Morris Brittan, Guerrero J Luis, Sullivan Suzanne M, Hung Judy, Levine Robert A
Cardiac Imaging Center, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
Division of Cardiology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea.
Methods Mol Biol. 2018;1816:295-308. doi: 10.1007/978-1-4939-8597-5_23.
Ischemic mitral regurgitation (IMR) is a common complication of ischemic heart disease that doubles mortality after myocardial infarction and is a major driving factor increasing heart failure. IMR is caused by left ventricular (LV) remodeling which displaces the papillary muscles that tether the mitral valve leaflets and restrict their closure. IMR frequently recurs even after surgical treatment. Failed repair associates with lack of reduction or increase in LV remodeling, and increased heart failure and related readmissions. Understanding mechanistic and molecular mechanisms of IMR has largely attributed to the development of large animal models. Newly developed therapeutic interventions targeted to the primary causes can also be tested in these models. The sheep is one of the most suitable models for the development of IMR. In this chapter, we describe the protocols for inducing IMR in sheep using surgical ligation of obtuse marginal branches. After successful posterior myocardial infarction involving posterior papillary muscle, animals develop significant mitral regurgitation around 2 months after the surgery.
缺血性二尖瓣反流(IMR)是缺血性心脏病的常见并发症,会使心肌梗死后的死亡率翻倍,并且是导致心力衰竭增加的主要驱动因素。IMR由左心室(LV)重塑引起,这种重塑会使固定二尖瓣小叶并限制其关闭的乳头肌移位。即使在手术治疗后,IMR也经常复发。修复失败与LV重塑未减轻或加重、心力衰竭增加及相关再入院有关。对IMR机制和分子机制的理解很大程度上归功于大型动物模型的开发。针对主要病因的新开发治疗干预措施也可在这些模型中进行测试。绵羊是开发IMR最合适的模型之一。在本章中,我们描述了使用钝缘支手术结扎在绵羊中诱导IMR的方案。在成功造成涉及后乳头肌的后心肌梗死后,动物在手术后约2个月会出现明显的二尖瓣反流。