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3D-Printed Coronary Implants Are Effective for Percutaneous Creation of Swine Models with Focal Coronary Stenosis

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Abstract

Reliable, closed-chest methods for creating large animal models of acute myocardial hypoperfusion are limited. We demonstrated the feasibility and efficacy of using magnetic resonance (MR)–compatible 3D-printed coronary implants for establishing swine models of myocardial hypoperfusion. We designed, manufactured, and percutaneously deployed implants in 13 swine to selectively create focal coronary stenosis. To test the efficacy of the implants to cause hypoperfusion or ischemia in the perfused territory, we evaluated regional wall motion, myocardial perfusion, and infarction using MR imaging. The overall swine survival rate was 85% (11 of 13). The implant retrieval rate was 92% (12 of 13). Fluoroscopic angiography confirmed focal stenosis. Cine and perfusion MRI showed regional wall motion abnormalities and inducible ischemia, respectively. Late gadolinium enhancement and histopathology showed no myocardial infarction. Our minimally invasive technique has promising applications for validation of new diagnostic methods in cardiac MR.

Our new minimally invasive, percutaneous method for creating swine models of acute focal coronary stenosis can be used for magnetic resonance imaging studies of myocardial ischemia. Comparable to existing methods in its efficacy and reliability, this rapid prototyping technique will allow researchers to more easily conduct translational cardiac imaging studies of coronary artery disease in large animal models.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

FOV:

Field of view

IHD:

Ischemic heart disease

MRI:

Magnetic resonance imaging

TE:

Echo time

TI:

Inversion time

TR:

Repetition time

TTC:

Triphenyltetrazolium chloride

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Acknowledgments

We thank staff members at the UCLA Lux Lab, the UCLA Translational Research Imaging Center (TRIC), and the Division of Laboratory Animal Medicine at UCLA for their assistance.

Funding

This work is supported by American Heart Association Transformational Award 18TPA34170049 and pilot funding from the Department of Radiology and Medicine at David Geffen School of Medicine at UCLA. K.L.N. is supported by funding from the American Heart Association (18TPA34170049), Veterans Health Administration (CX001901), and NIH (HL137562). O.A.A. is supported by NIH (HL142045). P.H. is supported by funding from NIH (HL127153), the American Heart Association (18TPA34170049), and the Veterans Health Administration (CX001901). R.D is supported by funding from NIH (HL133407, HL136578, and HL147133).

Author information

Authors and Affiliations

  1. Physics and Biology in Medicine Graduate Program, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Caroline M. Colbert, Peng Hu & Kim-Lien Nguyen

  2. Diagnostic Cardiovascular Imaging Laboratory, Department of Radiological Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Jiaxin Shao, Peng Hu & Kim-Lien Nguyen

  3. Division of Cardiology, David Geffen School of Medicine at UCLA and VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, MC 111E, Los Angeles, CA, 90073, USA

    John J. Hollowed, Jesse W. Currier & Kim-Lien Nguyen

  4. UCLA Cardiac Arrhythmia Center and Division of Cardiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Olujimi A. Ajijola

  5. Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Gregory A. Fishbein

  6. Division of Laboratory Animal Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Sandra M. Duarte-Vogel

  7. Biomedical Imaging Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center and Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Rohan Dharmakumar

Authors
  1. Caroline M. Colbert
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  2. Jiaxin Shao
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  3. John J. Hollowed
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  5. Olujimi A. Ajijola
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  7. Sandra M. Duarte-Vogel
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  9. Peng Hu
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  10. Kim-Lien Nguyen
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Contributions

Conception and design (KLN, PH, CMC), analysis and interpretation (CMC, KLN), data collection (CMC, KLN, JS, JHH, JWC, OAA, SMD, GAF), drafting the article (CMC, KLN), critical revision of the article (all authors), final approval of the article (all authors), overall responsibility (KLN)

Corresponding author

Correspondence to Kim-Lien Nguyen.

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Competing Interests

The authors declare that they have no competing interests.

Human Studies

No human studies were carried out by the authors for this article.

Animal Studies

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by our Institutional Animal Care and Use Committee (protocol no. 015-03D). With permission, S&S Farms supplied swine models purposely bred for biomedical research. S&S Farms Domestic pigs are a Yorkshire/Landrace hybrid originally derived from a specific pathogen-free herd.

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Associate Editor Adrian Chester oversaw the review of this article

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Clinical Relevance

Reliability of closed-chest techniques to create swine models of acute coronary stenosis remains limited. This work demonstrates the feasibility and efficacy of a rapid prototyping method using 3D-printed, heparin-coated, coronary stenosis implants to percutaneously create swine models of myocardial hypoperfusion and ischemia, which can be used to evaluate novel diagnostic MRI methods for ischemic coronary heart disease.

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Colbert, C.M., Shao, J., Hollowed, J.J. et al. 3D-Printed Coronary Implants Are Effective for Percutaneous Creation of Swine Models with Focal Coronary Stenosis. J. of Cardiovasc. Trans. Res. 13, 1033–1043 (2020). https://doi.org/10.1007/s12265-020-10018-3

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