A Pig Model of Myocardial Infarction: Catheter-Based Approaches
Despite enormous efforts in treating myocardial infarction (MI) and subsequent heart failure, the recent statistics from the American Heart Association evidently show that there still remains room for improvements. To develop and translate new therapeutics toward clinics, large animal models that allow us to test new therapies in human-like conditions are of extraordinary importance. In this chapter, we describe detailed protocols for the creation of a closed-chest MI model in pigs. The advantages of this model include high survival rate (>90% after ischemia–reperfusion), adjustable MI size depending on coronary occlusion site, reproducible cardiac dysfunction, and relatively low invasive method. The temporary coronary occlusion method for ischemia–reperfusion injury as well as the permanent occlusion method, using clot injection or embolic coil implantation, are described. Furthermore, we describe the key steps needed for understanding, performing, and analyzing cardiac angiography and echocardiography in pigs.
Key wordsMyocardial infarction in pigs Heart failure model Ischemia–reperfusion Embolic coil Permanent coronary occlusion Thrombus Cardiac angiography in pigs Echocardiography in pigs Large animal
This work is supported by NIH R01 HL139963 (K.I.), HL117505, HL 119046, HL129814, 128072, HL131404, HL135093, a P50 HL112324 (R.J.H.), AHA-SDG 17SDG33410873 (K.I.), and two Transatlantic Fondation Leducq grants. We would like to acknowledge the Gene Therapy Resource Program (GTRP) of the National Heart, Lung, and Blood Institute, National Institutes of Health. O.B. was supported by the Deutsche Herzstiftung.
- 2.Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2017) Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation 135(10):e146–e603. https://doi.org/10.1161/CIR.0000000000000485CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Houser SR, Margulies KB, Murphy AM, Spinale FG, Francis GS, Prabhu SD, Rockman HA, Kass DA, Molkentin JD, Sussman MA, Koch WJ, American Heart Association Council on Basic Cardiovascular Sciences, Council on Clinical Cardiology, Council on Functional Genomics and Translational Biology (2012) Animal models of heart failure: a scientific statement from the American Heart Association. Circ Res 111(1):131–150. https://doi.org/10.1161/RES.0b013e3182582523CrossRefPubMedGoogle Scholar
- 4.Lecour S, Botker HE, Condorelli G, Davidson SM, Garcia-Dorado D, Engel FB, Ferdinandy P, Heusch G, Madonna R, Ovize M, Ruiz-Meana M, Schulz R, Sluijter JP, Van Laake LW, Yellon DM, Hausenloy DJ (2014) ESC working group cellular biology of the heart: position paper: improving the preclinical assessment of novel cardioprotective therapies. Cardiovasc Res 104(3):399–411. https://doi.org/10.1093/cvr/cvu225CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Galvez-Monton C, Prat-Vidal C, Diaz-Guemes I, Crisostomo V, Soler-Botija C, Roura S, Llucia-Valldeperas A, Perea-Gil I, Sanchez-Margallo FM, Bayes-Genis A (2014) Comparison of two preclinical myocardial infarct models: coronary coil deployment versus surgical ligation. J Transl Med 12:137. https://doi.org/10.1186/1479-5876-12-137CrossRefPubMedPubMedCentralGoogle Scholar