Dual versus single vessel normothermic ex vivo perfusion of rat liver grafts using metamizole for vasodilatation.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
02
03
2020
accepted:
18
06
2020
entrez:
3
7
2020
pubmed:
3
7
2020
medline:
17
9
2020
Statut:
epublish
Résumé
Normothermic ex vivo liver perfusion (NEVLP) is a promising strategy to increase the donor pool in liver transplantation. Small animal models are essential to further investigate questions regarding organ preservation and reconditioning by NEVLP. A dual vessel small animal NEVLP (dNEVLP) model was developed using metamizole as a vasodilator and compared to conventional portovenous single vessel NEVLP (sNEVLP). Livers of male Wistar rats were perfused with erythrocyte-supplemented culture medium for six hours by either dNEVLP via hepatic artery and portal vein or portovenous sNEVLP. dNEVLP was performed either with or without metamizole treatment. Perfusion pressure and flow rates were constantly monitored. Transaminase levels were determined in the perfusate at the start and after three and six hours of perfusion. Bile secretion was monitored and bile LDH and GGT levels were measured hourly. Histopathological analysis was performed using liver and bile duct tissue samples after perfusion. Hepatic artery pressure was significantly lower in dNEVLP with metamizole administration. Compared to sNEVLP, dNEVLP with metamizole treatment showed higher bile production, lower levels of transaminases during and after perfusion as well as significantly lower necrosis in liver and bile duct tissue. Biochemical markers of bile duct injury showed the same trend. Our miniaturized dNEVLP system enables normothermic dual vessel rat liver perfusion. The administration of metamizole effectively ameliorates arterial vasospasm allowing for six hours of dNEVLP, with superior outcome compared to sNEVLP.
Sections du résumé
BACKGROUND
Normothermic ex vivo liver perfusion (NEVLP) is a promising strategy to increase the donor pool in liver transplantation. Small animal models are essential to further investigate questions regarding organ preservation and reconditioning by NEVLP. A dual vessel small animal NEVLP (dNEVLP) model was developed using metamizole as a vasodilator and compared to conventional portovenous single vessel NEVLP (sNEVLP).
METHODS
Livers of male Wistar rats were perfused with erythrocyte-supplemented culture medium for six hours by either dNEVLP via hepatic artery and portal vein or portovenous sNEVLP. dNEVLP was performed either with or without metamizole treatment. Perfusion pressure and flow rates were constantly monitored. Transaminase levels were determined in the perfusate at the start and after three and six hours of perfusion. Bile secretion was monitored and bile LDH and GGT levels were measured hourly. Histopathological analysis was performed using liver and bile duct tissue samples after perfusion.
RESULTS
Hepatic artery pressure was significantly lower in dNEVLP with metamizole administration. Compared to sNEVLP, dNEVLP with metamizole treatment showed higher bile production, lower levels of transaminases during and after perfusion as well as significantly lower necrosis in liver and bile duct tissue. Biochemical markers of bile duct injury showed the same trend.
CONCLUSION
Our miniaturized dNEVLP system enables normothermic dual vessel rat liver perfusion. The administration of metamizole effectively ameliorates arterial vasospasm allowing for six hours of dNEVLP, with superior outcome compared to sNEVLP.
Identifiants
pubmed: 32614897
doi: 10.1371/journal.pone.0235635
pii: PONE-D-20-06139
pmc: PMC7332079
doi:
Substances chimiques
Dipyrone
6429L0L52Y
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0235635Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Liver Transpl. 2018 Oct;24(10):1453-1469
pubmed: 30359490
Tissue Eng Part A. 2020 Jan;26(1-2):57-65
pubmed: 31364485
Front Pharmacol. 2019 Sep 11;10:996
pubmed: 31572180
Liver Transpl. 2016 Nov;22(11):1501-1508
pubmed: 27339754
Gastroenterol Clin North Am. 2011 Sep;40(3):641-58
pubmed: 21893278
Shock. 2005 Nov;24(5):421-7
pubmed: 16247327
J Plast Surg Hand Surg. 2016 Jun;50(3):151-5
pubmed: 26854097
J Hepatol. 2016 Dec;65(6):1245-1257
pubmed: 27486010
Liver Transpl. 2016 Nov;22(11):1573-1583
pubmed: 27556578
Transplantation. 2002 Mar 15;73(5):701-9
pubmed: 11907414
Liver Transpl. 2019 Feb;25(2):275-287
pubmed: 30341973
Am J Transplant. 2019 Sep;19(9):2661-2662
pubmed: 31062467
J Hepatol. 2011 May;54(5):1055-62
pubmed: 21145846
Transplantation. 2018 Apr;102(4):601-608
pubmed: 29189484
Liver Transpl. 2016 Jul;22(7):994-1005
pubmed: 26946466
Transpl Int. 2008 Aug;21(8):713-24
pubmed: 18492121
Int J Artif Organs. 2006 Feb;29(2):219-27
pubmed: 16552669
Am J Transplant. 2016 Jun;16(6):1779-87
pubmed: 26752191
Ann Surg. 2012 Mar;255(3):523-7
pubmed: 22323010
J Physiol. 2000 Oct 1;528 Pt 1:199-207
pubmed: 11018118
World J Hepatol. 2015 Nov 18;7(26):2636-47
pubmed: 26609341
J Hepatol. 2014 Dec;61(6):1267-75
pubmed: 25086285
Am J Transplant. 2018 Jan;18 Suppl 1:172-253
pubmed: 29292603
Tissue Eng. 2007 Aug;13(8):2143-51
pubmed: 17596120
J Surg Res. 2002 Apr;103(2):228-35
pubmed: 11922739
Transplantation. 1993 Sep;56(3):495-500
pubmed: 8212138
Liver Transpl. 2015 Aug;21(8):1040-50
pubmed: 25939487
PLoS One. 2015 Jul 15;10(7):e0131764
pubmed: 26177505
Am J Transplant. 2017 Apr;17(4):970-978
pubmed: 27805315
Curr Opin Organ Transplant. 2017 Dec;22(6):555-562
pubmed: 28922300
Liver Transpl. 2019 Mar;25(3):436-449
pubmed: 30362649
Transplant Direct. 2018 Oct 23;4(11):e400
pubmed: 30534591
J Surg Res. 2012 Apr;173(2):e83-8
pubmed: 22099594
Aliment Pharmacol Ther. 2007 Jun 15;25(12):1401-9
pubmed: 17539979
Pol J Vet Sci. 2014;17(1):207-14
pubmed: 24724493
Clin Liver Dis. 2017 May;21(2):289-301
pubmed: 28364814