N-acetylcysteine: a novel approach to methaemoglobinaemia in normothermic liver machine perfusion.

Autor: Clarke G; Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK. George.Clarke@uhb.nhs.uk.; Birmingham Biomedical Research Centre, National Institute for Health Research (NIHR), University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK. George.Clarke@uhb.nhs.uk.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TH, UK. George.Clarke@uhb.nhs.uk., Mao J; Birmingham Biomedical Research Centre, National Institute for Health Research (NIHR), University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TH, UK., Fan Y; Birmingham Biomedical Research Centre, National Institute for Health Research (NIHR), University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TH, UK., Hann A; Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK.; Birmingham Biomedical Research Centre, National Institute for Health Research (NIHR), University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TH, UK., Gupta A; Ochre-Bio Ltd, Oxford, UK., Nutu A; Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK., Buckel E; Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK., Kayani K; Birmingham Biomedical Research Centre, National Institute for Health Research (NIHR), University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TH, UK.; Queen Elizabeth Hospital Birmingham, Birmingham, B15 2TH, UK., Murphy N; Intensive Care Unit, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2TH, UK.; Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TH, UK., Bangash MN; Intensive Care Unit, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2TH, UK.; Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, B15 2TH, UK., Casey AL; Microbiology Department, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2TH, UK., Wootton I; Clinical Biochemistry, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2TH, UK., Lawson AJ; Clinical Biochemistry, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2TH, UK., Dasari BVM; Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK., Perera MTPR; Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK.; Birmingham Biomedical Research Centre, National Institute for Health Research (NIHR), University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TH, UK., Mergental H; Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK.; Birmingham Biomedical Research Centre, National Institute for Health Research (NIHR), University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TH, UK., Afford SC; Birmingham Biomedical Research Centre, National Institute for Health Research (NIHR), University of Birmingham and University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, UK.; Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TH, UK.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Nov 03; Vol. 13 (1), pp. 19022. Date of Electronic Publication: 2023 Nov 03.
DOI: 10.1038/s41598-023-45206-z
Abstrakt: Extended duration of normothermic machine perfusion (NMP) provides opportunities to resuscitate suboptimal donor livers. This intervention requires adequate oxygen delivery typically provided by a blood-based perfusion solution. Methaemoglobin (MetHb) results from the oxidation of iron within haemoglobin and represents a serious problem in perfusions lasting > 24 h. We explored the effects of anti-oxidant, N-acetylcysteine (NAC) on the accumulation of methaemoglobin. NMP was performed on nine human donor livers declined for transplantation: three were perfused without NAC (no-NAC group), and six organs perfused with an initial NAC bolus, followed by continuous infusion (NAC group), with hourly methaemoglobin perfusate measurements. In-vitro experiments examined the impact of NAC (3 mg) on red cells (30 ml) in the absence of liver tissue. The no-NAC group sustained perfusions for an average of 96 (range 87-102) h, universally developing methaemoglobinaemia (≥ 2%) observed after an average of 45 h, with subsequent steep rise. The NAC group was perfused for an average of 148 (range 90-184) h. Only 2 livers developed methaemoglobinaemia (peak MetHb of 6%), with an average onset of 116.5 h. Addition of NAC efficiently limits formation and accumulation of methaemoglobin during NMP, and allows the significant extension of perfusion duration.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje