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
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
19022Subventions
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
Références
Front Surg. 2021 Jan 28;8:634777
pubmed: 33598479
Crit Care Med. 2000 Apr;28(4):958-61
pubmed: 10809266
Am J Transplant. 2016 Jun;16(6):1779-87
pubmed: 26752191
Ann Hepatol. 2005 Apr-Jun;4(2):121-6
pubmed: 16010245
Nat Biotechnol. 2020 Feb;38(2):189-198
pubmed: 31932726
BMJ Open. 2017 Nov 28;7(11):e017733
pubmed: 29183928
Nat Biotechnol. 2022 Nov;40(11):1610-1616
pubmed: 35641829
Ann Emerg Med. 1996 Nov;28(5):499-503
pubmed: 8909270
Liver Transpl. 2022 Mar;28(3):493-496
pubmed: 34606663
West J Med. 2001 Sep;175(3):193-6
pubmed: 11527852
Am J Hematol. 2021 Dec 1;96(12):1666-1678
pubmed: 34467556
Nature. 2018 May;557(7703):50-56
pubmed: 29670285
Adv Pharmacol. 1997;38:205-27
pubmed: 8895810
Oxid Med Cell Longev. 2021 Dec 6;2021:3320325
pubmed: 34912495
Liver Transpl. 2018 Oct;24(10):1453-1469
pubmed: 30359490
Int J Mol Sci. 2021 Jul 14;22(14):
pubmed: 34299142
Curr Opin Pharmacol. 2007 Aug;7(4):355-9
pubmed: 17602868
JAMA Surg. 2022 Mar 01;157(3):189-198
pubmed: 34985503
Nat Commun. 2020 Jun 16;11(1):2939
pubmed: 32546694
Transplant Direct. 2021 Sep 07;7(10):e763
pubmed: 34514118
Pharmacol Ther. 2021 Dec;228:107916
pubmed: 34171332
Curr Mol Med. 2013 Jul;13(6):1000-9
pubmed: 23745587
Clin Pharmacokinet. 1991 Feb;20(2):123-34
pubmed: 2029805
Cell J. 2017 Apr-Jun;19(1):11-17
pubmed: 28367412
Am J Transplant. 2016 Nov;16(11):3235-3245
pubmed: 27192971