A novel cardioprotective perfusion protocol prevents functional decline during extended normothermic ex situ heart perfusion of porcine hearts.
| Autor: | Vervoorn MT; University Medical Center Utrecht. Department of Cardiothoracic Surgery. Division of Heart & Lungs. Utrecht, Netherlands., van Tuijl S; LifeTec Group B.V. Eindhoven, Netherlands., Ballan EM; University Medical Center Utrecht. Department of Cardiothoracic Surgery. Division of Heart & Lungs. Utrecht, Netherlands; University Medical Center Utrecht. Department of Cardiology. Laboratory of Experimental Cardiology. Division Heart & Lungs. Utrecht, Netherlands; Netherlands Heart Institute. Utrecht, Netherlands., Kaffka Genaamd Dengler SE; University Medical Center Utrecht. Department of Cardiothoracic Surgery. Division of Heart & Lungs. Utrecht, Netherlands., de Jager SCA; University Medical Center Utrecht. Department of Cardiology. Laboratory of Experimental Cardiology. Division Heart & Lungs. Utrecht, Netherlands., Sluijter JPG; University Medical Center Utrecht. Department of Cardiology. Laboratory of Experimental Cardiology. Division Heart & Lungs. Utrecht, Netherlands; Regenerative Medicine Utrecht. Circulatory Health Research Center. University Utrecht. Utrecht, Netherlands., Doevendans PA; Netherlands Heart Institute. Utrecht, Netherlands; University Medical Center Utrecht. Department of Cardiology. Division Heart & Lungs. Utrecht, Netherlands., van der Kaaij NP; University Medical Center Utrecht. Department of Cardiothoracic Surgery. Division of Heart & Lungs. Utrecht, Netherlands. Electronic address: N.p.vanderkaaij-2@umcutrecht.nl. |
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| Jazyk: | angličtina |
| Zdroj: | The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation [J Heart Lung Transplant] 2024 Oct 25. Date of Electronic Publication: 2024 Oct 25. |
| DOI: | 10.1016/j.healun.2024.10.016 |
| Abstrakt: | Introduction: A common limitation to normothermic ex situ heart perfusion (ESHP) is functional decline. We previously designed a cardioprotective normothermic perfusion protocol, incorporating adenosine-lidocaine cardioplegia, subnormothermic reperfusion, pyruvate and methylprednisolone supplementation, and hemofiltration to prevent myocardial functional decline over 4 hours. In this study, we added continuous catecholamine infusion and protective loading conditions to assess the effectiveness of this enhanced cardioprotective perfusion protocol in preventing functional decline during extended normothermic perfusion in marginal porcine hearts. Materials & Methods: Six slaughterhouse pig hearts underwent 9 hours of normothermic ESHP using the enhanced cardioprotective protocol. Cardiac function was assessed at 90, 120, 240, 360, 480 and 540 minutes of ESHP. Subsequently, a preload-challenge was conducted after 9 hours to assess preload-responsiveness (mimicking the Frank-Starling principle) and suitability for transplantation. Results: During perfusion, myocardial function remained stable, indicated by consistent mean cardiac index (9.2 L/min/kg at 90; 9.3 L/min/kg at 540 minutes of ESHP), left ventricular stroke work index (6258 mmHg*ml/kg at 90; 6707 mmHg*ml/kg at 540 minutes) and rate of ventricular pressure change over time. In response to a preload-challenge, there was a notable increase of 34% in mean cardiac index and 58% in mean stroke work. Conclusion: Our study demonstrates that the implementation of a cardioprotective protocol enables (very) marginal porcine slaughterhouse hearts, subjected to both a warm and cold ischemic insult prior to ESHP, to sustain satisfactory cardiac function without notable decline during 9 hours of normothermic ESHP, while also preserving their preload-responsiveness. The latter finding might indicate suitability for transplantation. This study provides a groundwork for further extending normothermic ESHP, unlocking the full potential of this promising technology. Competing Interests: Disclosure statement Sjoerd van Tuijl is an employee of LifeTec Group B.V. The other authors have no conflict of interest to report. This paper is supported by the partners of Regenerative Medicine Crossing Borders (RegMed XB), a public-private partnership that uses regenerative medicine strategies to cure common chronic diseases. This collaboration project is financed by the Dutch Heart Foundation and the Dutch Ministry of Economic Affairs by means of the public-private partnership allowance made available by the Top Sector Life Sciences & Health to stimulate public-private partnerships. (Copyright © 2024. Published by Elsevier Inc.) |
| Databáze: | MEDLINE |
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