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

• Published in: PloS one 2019-10, Vol.14 (10), p.e0224066-e0224066
• Main Authors: Boteon, Yuri L, Laing, Richard W, Schlegel, Andrea, Wallace, Lorraine, Smith, Amanda, Attard, Joseph, Bhogal, Ricky H, Reynolds, Gary, Perera, M Thamara PR, Muiesan, Paolo, Mirza, Darius F, Mergental, Hynek, Afford, Simon C
• Format: Article
• Language: English
• Subjects: Adenosine triphosphate; Adult; Aged; ATP; Bioenergetics; Biology and Life Sciences; Biomedical research; Blood Substitutes; Cadaver; Cold; Cold Ischemia; Electron transport; Energy Metabolism; Energy storage; Female; Hemoglobin; Hemoglobins - metabolism; Hospitals; Humans; Immunology; Immunotherapy; Injuries; Liver; Liver - blood supply; Liver - metabolism; Liver Transplantation; Liver transplants; Logistics; Male; Markers; Medical research; Medicine and Health Sciences; Middle Aged; Mitochondria; Organ Preservation - methods; Organs; Oxidative Stress; Oxygen; Oxygen - metabolism; Oxygenation; Perfusion; Perfusion - methods; Physical Sciences; Physiology; Reactive oxygen species; Reperfusion Injury - prevention & control; Spectrum analysis; Tissue Donors; Tissues; Viscosity; Warm Ischemia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0224066

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.