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The impact on the bioenergetic status and oxidative-mediated tissue injury of a combined protocol of hypothermic and normothermic machine perfusion using an acellular haemoglobin-based oxygen carrier: The cold-to-warm machine perfusion of the liver.
- Source :
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PloS one [PLoS One] 2019 Oct 23; Vol. 14 (10), pp. e0224066. Date of Electronic Publication: 2019 Oct 23 (Print Publication: 2019). - Publication Year :
- 2019
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Abstract
- Introduction: The combination of hypothermic and normothermic machine perfusion (HMP+NMP) of the liver provides individual benefits of both techniques, improving the rescue of marginal organs. The aim of this study was to investigate the effect on the bioenergetic status and the oxidative-mediated tissue injury of an uninterrupted combined protocol of HMP+NMP using a single haemoglobin-based oxygen carrier (HBOC)-based perfusate.<br />Methods: Ten discarded human donor livers had either 2 hours of dual hypothermic oxygenated perfusion (D-HOPE) with sequential controlled rewarming (COR) and then NMP using the HBOC-based perfusate uninterruptedly (cold-to-warm group); or 2 hours of hypothermic oxygenated perfusion (HOPE) with an oxygen carrier-free perfusate, followed by perfusate exchange and then NMP with an HBOC-based perfusate. Markers of liver function, tissue adenosine triphosphate (ATP) levels and tissue injury were systematically assessed.<br />Results: The hypothermic phase downregulated mitochondrial respiration and increased ATP levels in both groups. The cold-to-warm group presented higher arterial vascular resistance during rewarming/NMP (p = 0.03) with a trend of lower arterial flow (p = 0.09). At the end of NMP tissue expression of markers of reactive oxygen species production, oxidative injury and inflammation were comparable between the groups.<br />Conclusion: The uninterrupted combined protocol of HMP+NMP using an HBOC-based perfusate-cold-to-warm MP-mitigated the oxidative-mediated tissue injury and enhanced hepatic energy stores, similarly to an interrupted combined protocol; however, it simplified the logistics of this combination and may favour its clinical applicability.<br />Competing Interests: The machine perfusion research was funded by the Queen Elizabeth Hospital Birmingham Charity’s Liver Foundation UK. YLB is funded by the NIHR Wellcome Trust. Hemopure® was provided free of charge by Hemoglobin Oxygen Therapeutics LLC. The company has not had any role in the study design, data collection, analysis, interpretation or manuscript preparation. The authors are employees of the University Hospital Birmingham or the University of Birmingham and none of them received any payment or have any conflict of interest related to this manuscript. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.
- Subjects :
- Adult
Aged
Blood Substitutes
Cadaver
Female
Humans
Liver blood supply
Liver Transplantation
Male
Middle Aged
Oxidative Stress
Reperfusion Injury prevention & control
Tissue Donors
Cold Ischemia
Energy Metabolism
Hemoglobins metabolism
Liver metabolism
Organ Preservation methods
Oxygen metabolism
Perfusion methods
Warm Ischemia
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 14
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 31644544
- Full Text :
- https://doi.org/10.1371/journal.pone.0224066