title: Reduced glutathione in the liver as a potential viability marker in non-heart-beating donors.
abstract: Although the use of non-heart-beating donors (NHBD) is the oldest type of organ transplantation, the results were and still are disappointing. To consider using a liver from NHBD, it is of importance to assess the graft viability. Our aim was to assess the role of reduced liver glutathione (rGSHL) as a potential predictive marker of liver function before transplantation. Autotransplanted livers were subjected to 0, 60, and 90 minutes of ischemia in 20 pigs. We analyzed systemic cardiocirculatory parameters, bowel ischemia by endotoxin, endotoxin-neutralizing capacity, oxidative stress, hepatic perfusion parameters, liver enzymes, local bowel ischemia, and liver oxidative stress (rGSHL and oxidized glutathione in the liver). Autotransplantation was comparable to donor explantation/recipient transplantation with respect to systemic and hepatic parameters. Liver ischemia for 0, 60, and 90 minutes resulted in survival in 100% (NHBD-0), 71% (NHBD-60), and 57% (NHBD-90) of animals. Of all parameters, only hepatic microperfusion, pHi of the sigmoid colon, and bowel ischemia by endotoxin in the NHBD-90 group showed significant changes compared to NHBD-60 and control animals. Although systemic endotoxin-neutralizing capacity and total glutathione in erythrocytes levels were mainly influenced by cold perfusion, hepatic oxidative stress increased with ischemia time. The cut-off value of 11.5 ng/mmol of rGSHL could distinguish survivors from nonsurvivors, independent of the ischemia time. In conclusion, rGSHL has the potential of becoming an important viability marker, as it could predict survival in autotransplantation NHBD model regardless of the ischemia time. Further investigation to declare reasons for differing rGSHL levels within the liver is required.
authors.affiliation: Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Golling
authors.forename: Heidi
authors.initials: H
authors.lastname: Kellner
authors.forename: Hamidreza
authors.initials: H
authors.lastname: Fonouni
authors.forename: Morva Tahmasbi
authors.initials: MT
authors.lastname: Rad
authors.forename: Renate
authors.initials: R
authors.lastname: Urbaschek
authors.forename: Raoul
authors.initials: R
authors.lastname: Breitkreutz
authors.forename: Martha Maria
authors.initials: MM
authors.lastname: Gebhard
authors.forename: Arianeb
authors.initials: A
authors.lastname: Mehrabi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002102:Cadaver; D004731:Endotoxins / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006085:Graft Survival; D006801:Humans; D007511:Ischemia; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology / Q000628:therapy; D016031:Liver Transplantation / Q000379:methods*; D018384:Oxidative Stress; D013552:Swine; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004731:Endotoxins; D005978:Glutathione