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Myocardial infarction and intramyocardial injection models in swine

Nature Protocols volume 7, pages 1479–1496 (2012)Cite this article

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Abstract

Sustainable and reproducible large animal models that closely replicate the clinical sequelae of myocardial infarction (MI) are important for the translation of basic science research into bedside medicine. Swine are well accepted by the scientific community for cardiovascular research, and they represent an established animal model for preclinical trials for US Food and Drug Administration (FDA) approval of novel therapies. Here we present a protocol for using porcine models of MI created with a closed-chest coronary artery occlusion-reperfusion technique. This creates a model of MI encompassing the anteroapical, lateral and septal walls of the left ventricle. This model infarction can be easily adapted to suit individual study design and enables the investigation of a variety of possible interventions. This model is therefore a useful tool for translational research into the pathophysiology of ventricular remodeling and is an ideal testing platform for novel biological approaches targeting regenerative medicine. This model can be created in approximately 8–10 h.

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Figure 1: Flowchart depicting representative experimental timelines for acute chronic ICM.
Figure 2: Surgery, anesthesia and angiography equipment required for models of ischemic heart disease.
Figure 3: Cardiac MRI imaging techniques showing the extent of MI.
Figure 4: Neck vasculature and musculature of the swine.
Figure 5: Surgical dissection of the vasculature of the neck in the swine.
Figure 6: Vasculature access via a modified Seldinger technique.
Figure 7: Pressure-volume data obtained using a micromanometer conductance catheter.
Figure 8: Cardiac fluoroscopic and angiographic imaging depicting placement of diagnostic catheters and induction of MI.
Figure 9: Representative electrocardiographic changes during MI.
Figure 10: Surgical- and catheter-based injections of stem cells.
Figure 11: Representative pressure-volume loops before and after MI model creation.
Figure 12: Ventricular remodeling in the chronic MI model.

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Acknowledgements

This research is supported by US National Institutes of Health grants R01 HL094849, P20 HL101443, R01 HL084275, R01 HL107110, R01 HL110737 and U54 HL081028 (J.M.H.); and by the University of Miami Miller School of Medicine, Interdisciplinary Stem Cell Institute. The researchers would like to thank R. Gonzalez, D. Valdes, J. Rodriguez and M. Rosado for their technical contributions, and C. Sanina for her artistic contributions.

Author information

Authors and Affiliations

  1. Interdisciplinary Stem Cell Institute,

    Frederic C McCall, Kartik S Telukuntla, Vasileios Karantalis, Viky Y Suncion, Alan W Heldman & Joshua M Hare

  2. University of Miami Miller School of Medicine, Miami, Florida, USA

    Frederic C McCall, Kartik S Telukuntla, Vasileios Karantalis, Viky Y Suncion, Alan W Heldman & Joshua M Hare

  3. University of Miami Miller School of Medicine, Miami, Florida, USA

    Kartik S Telukuntla, Alan W Heldman, Muzammil Mushtaq, Adam R Williams & Joshua M Hare

  4. Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA

    Alan W Heldman, Muzammil Mushtaq & Joshua M Hare

  5. Department of Surgery,

    Adam R Williams

  6. University of Miami Miller School of Medicine, Miami, Florida, USA

    Adam R Williams

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Contributions

F.C.M. was involved in manuscript conception and design, creation/collection/assembly of data and manuscript writing; K.S.T. contributed to collection/assembly of data and manuscript writing; V.K. and V.Y.S. contributed equally to manuscript writing and editing, and to the creation and collection of data; A.W.H. and A.R.W. contributed to surgical and experimental conception and design, and to manuscript editing; M.M. was involved in manuscript writing; J.M.H., team leader, provided project and manuscript conception and design, financial support, manuscript writing and final approval of the manuscript.

Corresponding author

Correspondence to Joshua M Hare.

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Competing interests

Dr. Hare has a research grant from BioCardia and is listed as an inventor on a patent for cell therapy filed by the University of Miami. No other authors indicate competing financial interests.

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McCall, F., Telukuntla, K., Karantalis, V. et al. Myocardial infarction and intramyocardial injection models in swine. Nat Protoc 7, 1479–1496 (2012). https://doi.org/10.1038/nprot.2012.075

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