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Induced functional modulations of isolated large mammalian hearts

  • Organ Physiology
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Abstract

In this study we used Visible Heart® methodologies featuring cyclic temperature modulation of porcine hearts in order to establish characteristic temperature responses. This isolated and perfused model is a more predictable and modifiable analog for human heart preservation and isolates the response of the cardiac tissue. We comprehensively monitored isolated porcine hearts undergoing temperature change and demonstrated optimization of isolated cardiac function under mild hypothermia. We tracked metrics of cardiac function as continuous variables during temperature changes (~ 31 to 39 °C), eliciting a well-defined reduction in metabolic demand and in heart rate modulation. Optimization of function appeared to occur around 34.7 ± 0.9 °C (n = 13). Cardiac response was further investigated in the presence of active pacing in order to assess pacing capture and the heart’s functional response without a means of regulating rate. Our results may have direct clinical implications for emerging heart preservation methods prior to transplantation, as well as benefits for investigators using isolated heart models for preclinical device testing. Clinically, this porcine model is a basis for finding new ways to extend the window of viability for transplantable organs, thereby restoring or improving graft function and potentially enhancing recipient outcomes.

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Funding

Research was funded by a Medtronic research contract.

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Author notes

  1. Brian T. Howard

    Present address: Medtronic Inc., 8200 Coral Sea St NE, Mounds View, MN, 55112, USA

Authors and Affiliations

  1. Department of Surgery, University of Minnesota, 420 Delaware St. SE, B172 Mayo, MMC 195, Minneapolis, MN, 55455, USA

    Paul A. Iaizzo

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Correspondence to Paul A. Iaizzo.

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Conflict of interest

Paul Iaizzo has a research contract with Medtronic. Brian Howard is currently employed by Medtronic.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Care and Use Committee at the University of Minnesota.

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Howard, B.T., Iaizzo, P.A. Induced functional modulations of isolated large mammalian hearts. Pflugers Arch - Eur J Physiol 471, 1095–1101 (2019). https://doi.org/10.1007/s00424-019-02277-0

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  • DOI: https://doi.org/10.1007/s00424-019-02277-0

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