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

Autoři: Yuri L. Boteon aff001;  Richard W. Laing aff002;  Andrea Schlegel aff001;  Lorraine Wallace aff002;  Amanda Smith aff001;  Joseph Attard aff001;  Ricky H. Bhogal aff002;  Gary Reynolds aff002;  M. Thamara PR Perera aff001;  Paolo Muiesan aff001;  Darius F. Mirza aff001;  Hynek Mergental aff001;  Simon C. Afford aff002
Působiště autorů: Liver Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom aff001;  Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom aff002;  National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article



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.


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.


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.


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.

Klíčová slova:

Bile – Fatty liver – Inflammation – Liver – Liver transplantation – Mitochondria – Oxygen – Macrovesicular steatosis


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