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Liver Preservation (liver + preservation)
Selected AbstractsCold-induced apoptosis of rat liver cells in University of Wisconsin solution: The central role of chelatable ironHEPATOLOGY, Issue 3 2002Uta Kerkweg Although University of Wisconsin (UW) solution aims at the prevention of cold-induced cell injury, it failed to protect against cold-induced apoptosis of hepatocytes and liver endothelial cells: when incubated in UW solution at 4°C for 24 hours and subsequently rewarmed at 37°C, 72% ± 8% of rat hepatocytes and 81% ± 5% of liver endothelial cells lost viability. In both cell types, the observed cell damage occurred under an apoptotic morphology; it appeared to be mediated by a rapid increase in the cellular chelatable iron pool by a factor ,2 (as determined in hepatocytes) and subsequent formation of reactive oxygen species (ROS). Consequently, this cell injury was decreased by iron chelators to 6 to 25% (hepatocytes) and 4% ± 2% (liver endothelial cells). Deferoxamine nearly completely inhibited the occurrence of apoptotic morphology in both cell types. In liver endothelial cells, cold-induced apoptosis occurring during rewarming after 24 hours of cold incubation in UW solution was far more pronounced than in cell culture medium (loss of viability: 81% ± 5% vs. 28% ± 13%), but viability could even be maintained for 2 weeks of cold incubation by use of deferoxamine. In conclusion, this pathological mechanism might be an explanation for the strong endothelial cell injury known to occur after cold preservation. With regard to the extent of this iron-mediated injury, addition of a suitable iron chelator to UW solution might markedly improve the outcome of liver preservation. [source] Inhibition of TXA2 synthesis with OKY-046 improves liver preservation by prolonged hypothermic machine perfusion in ratsJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7pt2 2008Hongzhi Xu Abstract Background and Aim:, We previously reported that hypothermic machine perfusion (HMP) for liver preservation is feasible, but hepatic microcirculatory dysfunction and significant liver damage remain major obstacles in its application when the preservation is extended to 24 h. The underlying injury mechanism is not well understood. The present study sought to investigate the role of thromboxane A2 (TXA2) in the pathogenesis of liver injury after prolonged HMP. Methods:, Livers isolated from Sprague,Dawley rats were subjected to continuous machine perfusion with University of Wisconsin (UW) solution at a flow rate of 0.4 mL/min/g liver at 4°C for 24 h. A specific TXA2 synthase inhibitor, OKY-046 (OKY), was added to UW solution during the preservation period and to the Krebs,Henseleit buffer during reperfusion. The performance of the livers after preservation was evaluated using an isolated liver perfusion system with Krebs,Henseleit buffer at a flow rate of 15 mL/min at 37°C for 30 min. Results:, Prolonged HMP induced a significant release of TXA2 into the portal circulation as indicated by markedly increased levels of TXB2 in the perfusate during reperfusion (at 30 min, 1447.4 ± 163.6 pg/mL vs 50.91 ± 6.7 pg/mL for control). Inhibition of TXA2 synthesis with OKY significantly decreased releases of TXA2 (69.8 ± 13.4 pg/mL) concomitant with reduced lactate dehydrogenase (LDH) releases (at 30 min, HMP + OKY: 144.9 ± 27.9 U/L; HMP: 369.3 ± 68.5 U/L; simple cold storage or SCS: 884.4 ± 80.3 U/L), decreased liver wet/dry weight ratio (HMP + OKY vs SCS and HMP: 3.6 ± 0.3 vs 4.4 ± 0.1 and 3.9 ± 0.2, respectively) and increased hyaluronic acid uptake (at 30 min, HMP + OKY vs SCS, HMP: 33.1 ± 2.9% vs 13.9 ± 3.6%, 18.6 ± 2.4%, respectively). Liver histology also showed significant improvement in tissue edema and hepatocellular necrosis with OKY compared with HMP without OKY. Conclusion:, The results demonstrate that TXA2 is involved in the development of hepatocellular injury induced by HMP, and inhibition of TXA2 synthesis during preservation and reperfusion protects liver hepatocytes and sinusoidal endothelial cells from injuries caused by prolonged HMP. [source] Effect of apoE/ATP-containing liposomes on hepatic energy stateLIVER INTERNATIONAL, Issue 5 2003S. Chaïb Abstract: Background/Aims: ATP-containing liposomes partially prevent ATP depletion in the cold-stored liver. As hepatocytes can specifically bind apoE, we investigated whether the addition of apoE to large (200 nm) ATP-containing liposomes increases their uptake by the liver and further improves hepatic energy stores. Methods: Livers from fasted male Hartley guinea-pigs (231±3 g) were perfused for 90 min under our standard conditions (Control, n=6) or after a single bolus addition of plain liposomes (Lip, n=6), ATP (5 ,mol)-containing liposomes (ATP-Lip, n=6) or apoE/ATP-containing liposomes (0.8 or 8 mg apoE/g phospholipids; apoE1-Lip and apoE10-Lip, respectively, n=6 in each group). Liposome uptake and its impact on energy and nitrogen metabolism were studied. Results: At its highest concentration, apoE significantly increased liposome uptake (apoE10-Lip:,9.17±0.69 vs apoE1-Lip:,6.18±0.44 vs ATP-Lip:,6.40±0.88 nmol min,1 g,1; P<0.05). This was associated with a significant increase in intrahepatic ATP (apoE10-Lip: 1033±137 vs apoE1-Lip: 811±98 and ATP-Lip: 648±36 nmol g,1; P<0.05), which was restored to its level in non-perfused livers. Hepatic viability and nitrogen metabolism were not affected. Conclusions: Hepatic ATP content being a key factor in the maintenance of liver graft function, apoE/ATP-containing liposomes should be useful in liver preservation for transplantation. [source] Improved rat steatotic and nonsteatotic liver preservation by the addition of epidermal growth factor and insulin-like growth factor-I to University of Wisconsin solutionLIVER TRANSPLANTATION, Issue 9 2010M. Amine Zaouali This study examined the effects of epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) supplementation to University of Wisconsin solution (UW) in steatotic and nonsteatotic livers during cold storage. Hepatic injury and function were evaluated in livers preserved for 24 hours at 4°C in UW and in UW with EGF and IGF-I (separately or in combination) and then perfused ex vivo for 2 hours at 37°C. AKT was inhibited pharmacologically. In addition, hepatic injury and survival were evaluated in recipients who underwent transplantation with steatotic and nonsteatotic livers preserved for 6 hours in UW and UW with EGF and IGF-I (separately or in combination). The results, based on isolated perfused liver, indicated that the addition of EGF and IGF-I (separately or in combination) to UW reduced hepatic injury and improved function in both liver types. A combination of EGF and IGF-I resulted in hepatic injury and function parameters in both liver types similar to those obtained by EGF and IGF-I separately. EGF increased IGF-I, and both additives up-regulated AKT in both liver types. This was associated with glycogen synthase kinase-3, (GSK3,) inhibition in nonsteatotic livers and PPAR, overexpression in steatotic livers. When AKT was inhibited, the effects of EGF and IGF-I on GSK3,, PPAR,, hepatic injury and function disappeared. The benefits of EGF and IGF-I as additives in UW solution were also clearly seen in the liver transplantation model, because the presence of EGF and IGF-I (separately or in combination) in UW solution reduced hepatic injury and improved survival in recipients who underwent transplantation with steatotic and nonsteatotic liver grafts. In conclusion, EGF and IGF-I may constitute new additives to UW solution in steatotic and nonsteatotic liver preservation, whereas a combination of both seems unnecessary. Liver Transpl 16:1098,1111, 2010. © 2010 AASLD. [source] New concepts in liver preservation: How the pendulum sways back,LIVER TRANSPLANTATION, Issue 1 2009Thomas M. van Gulik [source] Histidine-tryptophan-ketoglutarate solution vs.LIVER TRANSPLANTATION, Issue 8 2007University of Wisconsin solution for liver transplantation: A systematic review University of Wisconsin (UW) solution has been recognized as the gold standard in liver preservation, but its limitations are becoming obvious, such as risk of biliary complications and its high cost. Alternatively, the effects of histidine-tryptophan-ketoglutarate (HTK), such as improved biliary protection and low cost, have been observed. This systematic review is conducted to compare the efficacy and safety of these 2 solutions. Databases from 1966 to June 2006 were searched. Randomized clinical trials (RCTs) and cohort studies comparing HTK and UW solutions for liver transplantation were included. Ten articles including 11 comparisons (1,200 patients) met the inclusion criteria, containing 2 RCTs and 9 cohort studies. No marked differences existed between the 2 groups in patient and graft survival rates, acute rejection, primary nonfunction, primary dysfunction, delayed graft function, and ALT and AST levels after transplantation. The only positive result was observed in the bile production after deceased donor liver transplantation (DDLT), which was statistically significantly higher in HTK group than that of UW group (95% confidence interval, 18.65-57.47; P = 0.0001). Although the difference in biliary complications between the 2 groups did not reach statistical significance, HTK was thought to be more effective for biliary tract flush and prevention of biliary complications in some studies. There was no statistically significant difference of effects (except bile production) between HTK and UW. But trends were documented in some studies for the superiority of HTK in biliary tract flush, prevention of biliary complications, and cost saving. Adequately powered RCTs with longer follow-up periods are required to evaluate the long-term effect of these 2 solutions. Liver Transpl 13:1125,1136, 2007. © 2007 AASLD. [source] In situ hypothermic liver preservation during radical liver resection with major vascular reconstructionBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 12 2009D. DuBay Background: The in situ hypothermic liver preservation technique may allow a more aggressive approach to tumours of the caval confluence and/or all three hepatic veins, which would otherwise be deemed irresectable. Methods: All descriptive data regarding patient demographics, operative characteristics, perioperative complications and outcomes of nine patients in whom this technique was used were collected prospectively. Results: Seven patients underwent liver trisegmentectomy and two had primary retrohepatic venal caval resection. Total hepatic vascular occlusion with in situ hypothermic liver preservation was used for venous reconstruction in all patients. The vena cava was reconstructed with prosthetic graft in seven patients. All main hepatic veins were reconstructed in the seven liver resections. In situ hypothermic liver preservation was well tolerated as evidenced by preserved hepatic synthetic function early after operation. One patient died 66 days after surgery. There were two recurrences after a median follow-up of 14 (range 2,33) months; local recurrence was identified in one patient after 4 months and distant metastasis in another after 8 months. Conclusion: The in situ hypothermic liver preservation technique appears to be a useful adjunct to radical hepatobiliary tumour excision procedures that require total hepatic vascular exclusion and major vascular reconstruction. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] | ||||||||||