BACKGROUND: Organ shortage in liver transplantation has justified usage of marginal donor livers to expand the donor organ pool. The particular susceptibility of steatotic livers to I/R injury necessitates optimal preservation conditions in order to minimize preservation-reperfusion injury for successful transplantation. METHODS: The effect of erythropoietin (EPO) as additive to HTK preservation solution was studied in a mouse model. Lean and steatotic livers were harvested, stored for 24 h in 4°C HTK solution containing either EPO or saline and reperfused for 2 h with 37°C Krebs-Henseleit buffer. Livers without cold storage served as sham controls. RESULTS: Flushing of livers upon cold storage revealed a transaminase release, which was 2- to 10-fold higher in steatotic versus lean livers. EPO was effective in reducing the enzyme release to 50% in steatotic but not in lean livers. EPO prevented cold storage-induced denudation of the endothelial lining in steatotic livers, but aggravated it in lean livers. During reperfusion, steatotic livers presented with lower oxygen consumption and higher enzyme release than lean livers. In all livers, parameters of reperfusion injury remained unaffected by EPO. Expression of UCP2 was found markedly higher in steatotic livers. After I/R, steatotic livers revealed a significant drop of UCP2, whereas expression in lean livers was only slightly affected. EPO diminished Erk phosphorylation to almost the same extent in both mouse strains. CONCLUSION: Fortification of the preservation solution by EPO ameliorates cold ischemic injury of steatotic livers and may thus be considered for use as an adjunctive agent to increase the success of transplanting steatotic livers.
BACKGROUND: Organ shortage in liver transplantation has justified usage of marginal donor livers to expand the donor organ pool. The particular susceptibility of steatotic livers to I/R injury necessitates optimal preservation conditions in order to minimize preservation-reperfusion injury for successful transplantation. METHODS: The effect of erythropoietin (EPO) as additive to HTK preservation solution was studied in a mouse model. Lean and steatotic livers were harvested, stored for 24 h in 4°C HTK solution containing either EPO or saline and reperfused for 2 h with 37°C Krebs-Henseleit buffer. Livers without cold storage served as sham controls. RESULTS: Flushing of livers upon cold storage revealed a transaminase release, which was 2- to 10-fold higher in steatotic versus lean livers. EPO was effective in reducing the enzyme release to 50% in steatotic but not in lean livers. EPO prevented cold storage-induced denudation of the endothelial lining in steatotic livers, but aggravated it in lean livers. During reperfusion, steatotic livers presented with lower oxygen consumption and higher enzyme release than lean livers. In all livers, parameters of reperfusion injury remained unaffected by EPO. Expression of UCP2 was found markedly higher in steatotic livers. After I/R, steatotic livers revealed a significant drop of UCP2, whereas expression in lean livers was only slightly affected. EPO diminished Erk phosphorylation to almost the same extent in both mouse strains. CONCLUSION: Fortification of the preservation solution by EPO ameliorates cold ischemic injury of steatotic livers and may thus be considered for use as an adjunctive agent to increase the success of transplanting steatotic livers.
Authors: J Wells Logan; Elizabeth N Allred; Raina N Fichorova; Stephen Engelke; Olaf Dammann; Alan Leviton Journal: Cytokine Date: 2014-06-02 Impact factor: 3.861
Authors: Linus Kebschull; Leon Franz Christoph Theilmann; Annika Mohr; Wencke Uennigmann; Sandra Stoeppeler; Barbara Heitplatz; Hans-Ullrich Spiegel; Ralf Bahde; Daniel Michael Palmes; Felix Becker Journal: Biosci Rep Date: 2017-12-05 Impact factor: 3.840
Authors: Maria Chalasti; Christos Iordanou; Zisis Kratiras; Aikaterini Stylianaki; Eleni-Andriana Trigka; Eleftheria Lakiotaki; Kali Makedou; Stavros Iliadis; Konstantinos G Zografos; Dimitrios Dimitroulis; Michail Chrisofos; Efstratios Patsouris; Georgios C Zografos; George C Bouboulis; Apostolos E Papalois Journal: J Int Med Res Date: 2020-06 Impact factor: 1.671