Abstract
BackgroundWaiting lists that continue to grow and the lack of organs available for transplantation necessitate the use of marginal livers, such as fatty livers. Since steatotic livers are more susceptible to damage from ischemia and reperfusion, it was investigated whether fatty livers with different lipidomic profiles show a different outcome when subjected to long-term cold storage preservation.MethodsEight-week-old male Wistar rats fed for 2 weeks by a methionine-choline-deficient (MCD) diet or control diet were employed in this study. Livers were preserved in a University of Wisconsin (UW) solution at 4 °C for 6, 12 or 24 h and, after washout, reperfused for 2 h with a Krebs-Henseleit buffer at 37 °C. Hepatic enzyme release, bile production, O2-uptake, and portal venous pressure (PVP) were evaluated. The liver fatty acid profile was evaluated by a gas chromatography-mass spectrometry (GC/MS).ResultsMCD rats showed higher LDH and AST levels with respect to the control group. When comparing MCD livers preserved for 6, 12 or 24 h, no differences in enzyme release were found during both the washout or the reperfusion period. The same trend occurred for O2-uptake, PVP, and bile flow. A general decrease in SFA and MUFA, except for oleic acid, and a decrease in PUFA, except for arachidonic, eicosadienoic, and docosahexanaeoic acids, were found in MCD rats when compared with control rats. Moreover, the ratio between SFA and the various types of unsaturated fatty acids (UFA) was significantly lower in MCD rats.ConclusionsAlthough prolonged cold ischemia negatively affects the graft outcome, our data suggest that the quality of lipid constituents could influence liver injury during cold storage: the lack of an increased hepatic injury in MCD may be justified by low SFA, which likely reduces the deleterious tendency toward lipid crystallization occurring under cold ischemia.
Highlights
Waiting lists that continue to grow and the lack of organs available for transplantation necessitate the use of marginal livers, such as fatty livers
Cold storage preservation and reperfusion injury in livers from MCD rats When comparing livers obtained from MCD rats, no differences in enzyme release were found after 6, 12- or 24-h cold storage (CS) preservation both during the washout or reperfusion (Fig. 2)
A significant increase in Aspartate aminotransaminase (AST) and Lactate dehydrogenase (LDH) release was found in control livers preserved for 24 h when compared with those preserved for 6 h (Fig. 2A and B)
Summary
Waiting lists that continue to grow and the lack of organs available for transplantation necessitate the use of marginal livers, such as fatty livers. Since steatotic livers are more susceptible to damage from ischemia and reperfusion, it was investigated whether fatty livers with different lipidomic profiles show a different outcome when subjected to long-term cold storage preservation. Given the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), steatotic livers represent a valid alternative to meeting the demand for organ transplantation [1]. Hepatic steatosis is categorized as macrovesicular or microvesicular. The latter appears to be less correlated with a poor transplant outcome due to primary non-function (PNF) [3]. Organs are often discarded when the steatosis is associated with other risk factors, such as the advanced age of the donor and prolonged cold storage (CS) preservation time [5]
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