Bile Analysis as a Tool for Assessing Integrity of Biliary Epithelial Cells after Cold Ischemia–Reperfusion of Rat Livers

Vajdová, Katarína; Smreková, Renáta; Kukan, M; Lutterová, Martina; Wsólová, Ladislava

doi:10.1006/cryo.2000.2276

Cited by 47 publications

(39 citation statements)

References 17 publications

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“…For this purpose, bile samples were collected under mineral oil and analyzed immediately using an ABL800 FLEX analyzer (Radiometer). Biliary concentration of gamma-GT and lactate dehydrogenase (LDH) were measured as biomarkers of biliary epithelial cell injury (13), and biliary bilirubin concentration was measured as biomarker of hepatocellular secretory function, using standard biochemical methods.…”

Section: Liver Function Assessmentmentioning

confidence: 99%

Ex vivo Normothermic Machine Perfusion and Viability Testing of Discarded Human Donor Livers

Dries

Karimian

Sutton

et al. 2013

American Journal of Transplantation

254

212

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In contrast to traditional static cold preservation of donor livers, normothermic machine perfusion may reduce preservation injury, improve graft viability and potentially allows ex vivo assessment of graft viability before transplantation. We have studied the feasibility of normothermic machine perfusion in four discarded human donor livers. Normothermic machine perfusion consisted of pressure and temperature controlled pulsatile perfusion of the hepatic artery and continuous portal perfusion for 6 h. Two hollow fiber membrane oxygenators provided oxygenation of the perfusion fluid. Biochemical markers in the perfusion fluid reflected minimal hepatic injury and improving function. Lactate levels decreased to normal values, reflecting active metabolism by the liver (mean lactate 10.0 ± 2.3 mmol/L at 30 min to 2.3 ± 1.2 mmol/L at 6 h). Bile production was observed throughout the 6 h perfusion period (mean rate 8.16 ± 0.65 g/h after the first hour). Histological examination before and after 6 h of perfusion showed well-preserved liver morphology without signs of additional hepatocellular ischemia, biliary injury or sinusoidal damage. In conclusion, this study shows that normothermic machine perfusion of human donor livers is technically feasible. It allows assessment of graft viability before transplantation, which opens new avenues for organ selection, therapeutic interventions and preconditioning.

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Section: Liver Function Assessmentmentioning

confidence: 99%

Ex vivo Normothermic Machine Perfusion and Viability Testing of Discarded Human Donor Livers

Dries

Karimian

Sutton

et al. 2013

American Journal of Transplantation

254

212

View full text Add to dashboard Cite

show abstract

“…Biliary concentration of gamma-glutamyltransferase (GGT) and LDH were measured as biomarkers of biliary epithelial cell injury, 21 and biliary bilirubin concentration was measured as a biomarker of hepatocellular secretory function, 21 using standard biochemical methods.…”

Section: Biochemical Markers Of Function and Injurymentioning

confidence: 99%

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

Westerkamp

Mahboub²,

Meyer

et al. 2015

Liver Transpl

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A short period of oxygenated machine perfusion (MP) after static cold storage (SCS) may reduce biliary injury in donation after cardiac death (DCD) donor livers. However, the ideal perfusion temperature for protection of the bile ducts is unknown. In this study, the optimal perfusion temperature for protection of the bile ducts was assessed. DCD rat livers were preserved by SCS for 6 hours. Thereafter, 1 hour of oxygenated MP was performed using either hypothermic machine perfusion, subnormothermic machine perfusion, or with controlled oxygenated rewarming (COR) conditions. Subsequently, graft and bile duct viability were assessed during 2 hours of normothermic ex situ reperfusion. In the MP study groups, lower levels of transaminases, lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances were measured compared to SCS. In parallel, mitochondrial oxygen consumption and adenosine triphosphate (ATP) production were significantly higher in the MP groups. Biomarkers of biliary function, including bile production, biliary bicarbonate concentration, and pH, were significantly higher in the MP groups, whereas biomarkers of biliary epithelial injury (biliary gamma-glutamyltransferase [GGT] and LDH), were significantly lower in MP preserved livers. Histological analysis revealed less injury of large bile duct epithelium in the MP groups compared to SCS. In conclusion, compared to SCS, end-ischemic oxygenated MP of DCD livers provides better preservation of biliary epithelial function and morphology, independent of the temperature at which MP is performed. End-ischemic oxygenated MP could reduce biliary injury after DCD liver transplantation. Liver Transpl 21:1300-1311, 2015. V C 2015 AASLD.Received March 17, 2015; accepted June 8, 2015.Ischemic cholangiopathy, also known as nonanastomotic biliary strictures (NAS), is one of the most prevalent and troublesome complications after liver transplantation. During NAS formation, in particular, the large (extrahepatic) bile ducts become fibrotic and/or necrotic. Patients with NAS may suffer from recurrent jaundice and episodes of cholangitis, and retransplantation may be the only curative treatment. 1 The combination of ischemia and ischemia/ reperfusion (I/R) injury has been shown to be a major Additional supporting information may be found in the online version of this article.

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“…13 Evaluation of the storage solution has also been performed using survival of animals after transplantation, 2,6,[14][15][16] morphologic studies of stored tissue, 17,18 biochemical studies such as leakage of lactate dehydrogenase, 19 membrane potential measurements, 20 and bile analysis. 21,22 In addition, systems with cultured cells have been used. 19,23 In the present study, we propose x-ray microanalysis for evaluation of the tissue in the storage solution.…”

mentioning

confidence: 99%

Preservation of mouse liver tissue during cold storage in experimental solutions assessed by x-ray microanalysis

Kozlova

Khalid

Roomans

2003

Liver Transplantation

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The increasing use of organs for transplantation necessitates the development of optimal preservation techniques. The goal of this study was to investigate changes in elemental content in mouse liver cells during cold storage by x-ray microanalysis in parallel with morphologic studies. Tissue was stored at 4°C for 4 to 12 hours in normal Krebs-Ringer solution (high sodium/potassium ratio), modified Krebs-Ringer solution (low Na ؉ /K ؉ ratio), Euro-Collins solution, University of Wisconsin (UW) solution, or seven modified versions of the UW solution. Incubation of liver in normal Krebs-Ringer solution caused a significant increase in sodium and decrease in potassium concentrations in contrast to incubation in other solutions. The concentration of sodium, potassium, and chlorine in the cells closely followed the concentration in the storage solution, indicating that the intracellular concentration of these ions during storage is entirely dependent on diffusion processes. The calcium concentration was independent of the storage solution used. Studies by light and transmission electron microscopy showed good preservation of hepatocytes after storage for 8 and 12 hours in UW solution and its variants, modified KrebsRinger solution and Euro-Collins solution, but showed moderate damage to mitochondria and swelling of the endoplasmic reticulum in normal Krebs-Ringer solution. In addition, damage to the sinusoidal endothelial cells was observed after 4 hours in normal Krebs-Ringer solution and after 8 to 12 hours in the other solutions. In conclusion, the only factor determining the intracellular concentration of diffusible ions after cold tissue storage is the ionic composition of the extracellular medium. X-ray microanalysis provides an objective method for assessing whether the intracellular ionic composition of tissue is maintained during storage. (Liver Transpl 2003;9: 268-278.)A persistent problem in organ transplantation is the tissue damage that occurs during organ preservation. University of Wisconsin (UW) solution is considered one of the most effective cold storage solutions and allows successful preservation of the liver. 1-3 UW solution was first developed experimentally for pancreas transplantation 4,5 and only later applied to the preservation of liver, heart, 2,6 and lung. 7 Liver grafts have been preserved for as long as 24 hours, still offering a thriving transplantation and satisfactory bile production. 8 Liver transplantation has been made more effective with UW solution, and the time of preservation of the liver and pancreas has been significantly increased compared with earlier solutions used for simple cold storage. 9,10 Still, it has been suggested that a cold ischemia for more than 12 hours is a great hazard for the recipient. 11,12 It has been suggested that further developments of graft preservation solutions should concentrate on specific organ requirements and not on grafts in general. 2 ␤-Galactosidase has been proposed as a marker of ischemia-reperfusion injury in the liver because Kupffer ...

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Bile Analysis as a Tool for Assessing Integrity of Biliary Epithelial Cells after Cold Ischemia–Reperfusion of Rat Livers

Cited by 47 publications

References 17 publications

Ex vivo Normothermic Machine Perfusion and Viability Testing of Discarded Human Donor Livers

Ex vivo Normothermic Machine Perfusion and Viability Testing of Discarded Human Donor Livers

End‐ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature

Preservation of mouse liver tissue during cold storage in experimental solutions assessed by x-ray microanalysis

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