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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
03 11 2023
Historique:
received: 30 04 2023
accepted: 17 10 2023
medline: 6 11 2023
pubmed: 4 11 2023
entrez: 4 11 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37923778
doi: 10.1038/s41598-023-45206-z
pii: 10.1038/s41598-023-45206-z
pmc: PMC10624848
doi:

Substances chimiques

Acetylcysteine WYQ7N0BPYC
Methemoglobin 9008-37-1

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

19022

Subventions

Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom

Informations de copyright

© 2023. The Author(s).

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Auteurs

George 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.

Jingwen 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.

Yiyu 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.

Angus 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.

Amita Gupta (A)

Ochre-Bio Ltd, Oxford, UK.

Anisa Nutu (A)

Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK.

Erwin Buckel (E)

Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK.

Kayani 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.

Nicholas 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.

Mansoor N 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.

Anna L Casey (AL)

Microbiology Department, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2TH, UK.

Isla Wootton (I)

Clinical Biochemistry, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2TH, UK.

Alexander J Lawson (AJ)

Clinical Biochemistry, Queen Elizabeth Hospital Birmingham, Birmingham, B15 2TH, UK.

Bobby V M Dasari (BVM)

Liver Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn Way, Birmingham, B15 2TH, UK.

M Thamara P R 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.

Hynek 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.

Simon C 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.

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