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Cardiac remodeling in a new pig model of chronic heart failure: Assessment of left ventricular functional, metabolic, and structural changes using PET, CT, and echocardiography

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Journal of Nuclear Cardiology Aims and scope

Abstract

Aims

Large animal models are needed to study disease mechanisms in heart failure (HF). In the present study we characterized the functional, metabolic, and structural changes of myocardium in a novel pig model of chronic myocardial infarction (MI) by using multimodality imaging and histology.

Methods and Results

Male farm pigs underwent a two-step occlusion of the left anterior descending coronary artery with concurrent distal ligation and implantation of a proximal ameroid constrictor (HF group), or sham operation (control group). Three months after the operation, cardiac output and wall stress were measured by echocardiography. Left ventricle (LV) volumes and mass were measured by computed tomography (CT). Myocardial perfusion was evaluated by [15O]water and oxygen consumption using [11C]acetate positron emission tomography, and the efficiency of myocardial work was calculated. Histological examinations were conducted to detect MI, hypertrophy, and fibrosis. Animals in the HF group had a large anterior MI scar. CT showed larger LV diastolic volume and lower ejection fraction in HF pigs than in controls. Perfusion and oxygen consumption in the remote non-infarcted myocardium were preserved in HF pigs as compared to controls. Global LV work and efficiency were significantly lower in HF than control pigs and was associated with increased wall stress. Histology showed myocyte hypertrophy but not increased interstitial fibrosis in the remote segments in HF pigs.

Conclusions

The chronic post-infarction model of HF is suitable for studies aimed to evaluate LV remodeling and changes in oxidative metabolism and can be useful for testing new therapies for HF.

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Acknowledgments

The authors wish to thank the staff of the Turku PET Centre for performing the required PET imaging and laboratory measurements. The authors would also like to thank Mrs Liisa Lempiäinen for the preparation of histological samples, M.Sc. Juho Virtanen for developing histological analysis methods, and Ms Piia Tuomisto for helping in animal experiments.

Disclosure

The authors report no conflict of interest.

Author information

Authors and Affiliations

  1. Turku PET Centre, University of Turku and Turku University Hospital, Kiinamyllynkatu 4-8, 20521, Turku, Finland

    Miikka Tarkia MSc, Matti Haavisto BM, Virva Saunavaara PhD, Tuula Tolvanen MSc, Mika Teräs PhD, Johanna Rokka MSc, Anne Roivainen PhD, Antti Saraste MD, PhD & Juhani Knuuti MD, PhD

  2. Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland

    Christoffer Stark MD, Rasmus Kentala BM, Tommi Vähäsilta MD, PhD & Timo Savunen MD, PhD

  3. Heart Center, Turku University Hospital and University of Turku, Turku, Finland

    Christoffer Stark MD, Tommi Vähäsilta MD, PhD, Timo Savunen MD, PhD, Marjatta Strandberg MD, PhD, Mikko Pietilä MD, PhD & Antti Saraste MD, PhD

  4. Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University Hospital, Turku, Finland

    Ville-Veikko Hynninen MD, PhD

  5. Department of Forensic Medicine, University of Turku, Turku, Finland

    Pekka Saukko MD, PhD

  6. Turku Center for Disease Modeling, University of Turku, Turku, Finland

    Anne Roivainen PhD

  7. Institute of Clinical Medicine, University of Turku, Turku, Finland

    Antti Saraste MD, PhD

Authors
  1. Miikka Tarkia MSc
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  2. Christoffer Stark MD
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  16. Antti Saraste MD, PhD
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  17. Juhani Knuuti MD, PhD
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Corresponding author

Correspondence to Miikka Tarkia MSc.

Additional information

Funding

This work was supported by Tekes—the Finnish Funding Agency for Technology Innovation, by the Finnish Cultural Foundation and Finnish foundation for cardiovascular research. It was conducted in the Finnish Centre of Excellence in Cardiovascular and Metabolic Diseases supported by the Academy of Finland, University of Turku, Turku University Hospital, and Åbo Akademi University. Miikka Tarkia is a PhD student supported by the University of Turku Graduate School Drug Research Doctoral Programme.

See related editorials, doi:10.1007/s12350-015-0081-z and doi:10.1007/s12350-015-0078-7.

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Tarkia, M., Stark, C., Haavisto, M. et al. Cardiac remodeling in a new pig model of chronic heart failure: Assessment of left ventricular functional, metabolic, and structural changes using PET, CT, and echocardiography. J. Nucl. Cardiol. 22, 655–665 (2015). https://doi.org/10.1007/s12350-015-0068-9

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  • DOI: https://doi.org/10.1007/s12350-015-0068-9

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