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Translational large animal model of hibernating myocardium: characterization by serial multimodal imaging

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Abstract

Nonrevascularizable coronary artery disease is a frequent cause of hibernating myocardium leading to heart failure (HF). Currently, there is a paucity of therapeutic options for patients with this condition. There is a lack of animal models resembling clinical features of hibernating myocardium. Here we present a large animal model of hibernating myocardium characterized by serial multimodality imaging. Yucatan minipigs underwent a surgical casein ameroid implant around the proximal left anterior descending coronary artery (LAD), resulting in a progressive obstruction of the vessel. Pigs underwent serial multimodality imaging including invasive coronary angiography, cardiac magnetic resonance (CMR), and hybrid 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT). A total of 43 pigs were operated on and were followed for 120 ± 37 days with monthly multimodality imaging. 24 pigs (56%) died during the follow-up. Severe LAD luminal stenosis was documented in all survivors. In the group of 19 long-term survivors, 17 (90%) developed left ventricular systolic dysfunction [median LVEF of 35% (IQR 32.5–40.5%)]. In 17/17, at-risk territory was viable on CMR and 14 showed an increased glucose uptake in the at-risk myocardium on 18FDG-PET/CT. The present pig model resembles most of the human hibernated myocardium characteristics and associated heart failure (systolic dysfunction, viable myocardium, and metabolic switch to glucose). This human-like model might be used to test novel interventions for nonrevascularizable coronary artery disease and ischemia heart failure as a previous stage to clinical trials.

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Acknowledgements

This study has been partially funded by the Horizon 2020 European Research Area Network on Cardiovascular Diseases (ERA-CVD) Joint Transnational Call “AC16/00021: FAT4HEART,” by the Spanish Society of Cardiology through a “Translational Research grant 2019,” and by the Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) through a FIS grant (Ref # PI16/02110). Imaging phenotyping was partially supported by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofunded with European structural and investment funds. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).

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Authors and Affiliations

  1. Translational Laboratory for Cardiovascular Imaging and Therapy, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), C/ Melchor Fernandez Almagro 3, Madrid, 28029, Spain

    Juan Martínez-Milla, Carlos Galán-Arriola, Manuel Carnero, Javier Cobiella, Daniel Pérez-Camargo, Victor Bautista-Hernández, Rocío Villena-Gutierrez, Manuel Lobo, Jesús Mateo, Jean Paul Vilchez-Tschischke, Beatriz Salinas, Lorena Cussó, Gonzalo Javier López, Valentín Fuster, Manuel Desco & Borja Ibanez

  2. Department of Cardiology, IIS-Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain

    Juan Martínez-Milla & Borja Ibanez

  3. Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain

    Carlos Galán-Arriola, Montserrat Rigol, Nuria Solanes & Borja Ibanez

  4. Department of Cardiovascular Surgery, Hospital Clínico San Carlos, Madrid, Spain

    Manuel Carnero, Javier Cobiella & Daniel Pérez-Camargo

  5. Complejo Hospitalario Universitario A Coruña,, A Coruña, Spain

    Victor Bautista-Hernández

  6. August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Institut de Malalties Cardiovasculars, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain

    Montserrat Rigol & Nuria Solanes

  7. Department of Cardiology, Complejo Hospitalario Ruber Juan Bravo, Madrid, Spain

    Jean Paul Vilchez-Tschischke

  8. Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid, Madrid, Spain

    Beatriz Salinas, Lorena Cussó & Manuel Desco

  9. Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

    Beatriz Salinas, Lorena Cussó & Manuel Desco

  10. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain

    Beatriz Salinas, Lorena Cussó & Manuel Desco

  11. Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Valentín Fuster

  12. Philips Healthcare, Madrid, Spain

    Javier Sanchez-González

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  1. Juan Martínez-Milla
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  2. Carlos Galán-Arriola
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  18. Javier Sanchez-González
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  19. Borja Ibanez
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Correspondence to Borja Ibanez.

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Javier Sanchez-González is a Philips employee. The rest of authors declare that they have no conflict of interest.

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Martínez-Milla, J., Galán-Arriola, C., Carnero, M. et al. Translational large animal model of hibernating myocardium: characterization by serial multimodal imaging. Basic Res Cardiol 115, 33 (2020). https://doi.org/10.1007/s00395-020-0788-0

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