Abstract
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.
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Acknowledgments
This study was supported in part by NIH grants R01 HL128099 and HL141917, and by support from the Ellison Foundation, Boston, MA.
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Movie clips of baseline (normal) short axis images (a, b) and posterior infarction with PM involvement (c, d, and e). The PM does not contract; not moving toward the center in short axis (c, d) and the base in long axis (e) (MP4 520 kb)
Movie clips of baseline (normal) short axis images (a, b) and posterior infarction with PM involvement (c, d, and e). The PM does not contract; not moving toward the center in short axis (c, d) and the base in long axis (e) (MP4 537 kb)
Movie clips of baseline (normal) short axis images (a, b) and posterior infarction with PM involvement (c, d, and e). The PM does not contract; not moving toward the center in short axis (c, d) and the base in long axis (e) (MP4 550 kb)
Movie clips of baseline (normal) short axis images (a, b) and posterior infarction with PM involvement (c, d, and e). The PM does not contract; not moving toward the center in short axis (c, d) and the base in long axis (e) (MP4 541 kb)
Movie clips of baseline (normal) short axis images (a, b) and posterior infarction with PM involvement (c, d, and e). The PM does not contract; not moving toward the center in short axis (c, d) and the base in long axis (e) (MP4 714 kb)
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Kim, DH., Morris, B., Guerrero, J.L., Sullivan, S.M., Hung, J., Levine, R.A. (2018). Ovine Model of Ischemic Mitral Regurgitation. In: Ishikawa, K. (eds) Experimental Models of Cardiovascular Diseases. Methods in Molecular Biology, vol 1816. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8597-5_23
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