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. Liver Transpl 14: [1637][1638][1639][1640][1641][1642][1643][1644][1645][1646][1647] 2008. © 2008 AASLD. Received March 13, 2008; accepted June 5, 2008.The use of non-heart-beating donors (NHBD) is the oldest type of solid organ transplantation. With respect to the liver, an important organ, results have been disappointing. Primary liver nonfunction (PNF) is dependent on the donor being in a stable/controlled or unstable/uncontrolled stage. Transplantation from uncontrolled NHBD results in 50%-75% of livers having PNF and a 6-month graft survival of between 17% and 50%.1,2 In adult controlled NHBD, 1-year and 3-year liver graft survival improved up to 69% and 59%, respectively, 3,4 whereas pediatric graft survival from controlled NHBD can now reach 1-year and 5-year graft survival rates of 89% and 79%, respectively.5 Despite this progress, wider application of such livers is under Abbreviations: AF, aortic flow; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ATx, autotransplantation; CVP, central venous pressure; ENC, endotoxin-neutralizing capacity; GSH, glutathione; GSSG, oxidized glutathione; GSSG E , oxidized glutathione in erythrocytes; GSSG L , oxidized glutathione in the liver; HAF, hepatic artery flow; i.v., intravenously; IVC, inferior vena ca...

Exact CT-Based Liver Volume Calculation Including Nonmetabolic Liver Tissue in Three-Dimensional Liver Reconstruction

“…They were housed at the Animal Resource Service Facilities at the University of Heidelberg according to the procedures outlined in the Guide for the Care and Use of Laboratory Animals, prepared by the National Academy of Sciences. The anesthetic protocol we followed is standardized and has been used for many years in different porcine studies [28,29]. After initial sedation by intramuscular injection of 5.0 mg/kg ketamine hydrochloride (Ketanest S; Pfizer, Freiburg, Germany), 0.1 mg/kg midazolam (Dormicum; Roche, Mannheim, Germany), and 0.5 mg/kg azaperon (Stresnil; Jansen-Cilag, Neuss, Germany), general anaesthesia was induced with tracheal intubation and a mixture of oxygen, nitrous oxide and isoflurane (Abbott, Chicago, IL).…”

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“…66 In addition, other biomarkers, including xanthine, hypoxanthine, hyaluronic acid, and reduced glutathione have been suggested for the assessment of graft viability. [67][68][69][70][71] Therefore, evaluating these biomarkers in DCD liver grafts prior to implant would be helpful. However, some technical limitations (such as the inability to identify these biomarkers in peripheral body fluids), technical demands, and time constraints in the clinical setting preclude these biomarkers from being incorporated into current practice.…”

Advances in the management of the explanted donor liver

“…87 Other potential parameters for liver damage tested in animal models of extracorporeal liver perfusion include levels of lactate dehydrogenase and βgalactosidase, g lutathioneStransferase, glutamate dehydrogenase, hyalu ronic acid, liver glutathione, alanine and histi dine. [88][89][90][91][92][93] In one study, the authors delineated a change in bile fluid composition in machine perfused livers from rabbits after warm ischaemia. 94 Several functional tests for measurement of meta bolic performance of the liver can be used.…”