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Schewe, Julia; Makeschin, Marie-Christine; Khandoga, Andrej; Zhang, Jiang; Mayr, Doris; Rothenfußer, Simon; Schnurr, Max; Gerbes, Alexander L. and Steib, Christian J. (2020): To Protect Fatty Livers from Ischemia Reperfusion Injury: Role of Ischemic Postconditioning. In: Digestive diseases and sciences, Vol. 66: pp. 1349-1359 [PDF, 1MB]


BACKGROUND The benefit of ischemic postconditioning (IPostC) might be the throttled inflow following cold ischemia. The current study investigated advantage and mechanisms of IPostC in healthy and fatty rat livers. METHODS Male SD rats received a high-fat diet to induce fatty livers. Isolated liver perfusion was performed after 24 h ischemia at 4°C as well as in vivo experiments after 90 min warm ischemia. The so-called follow-up perfusions served to investigate the hypothesis that medium from IPostC experiments is less harmful. Lactate dehydrogenase (LDH), transaminases, different cytokines, and gene expressions, respectively, were measured. RESULTS Fatty livers showed histologically mild inflammation and moderate to severe fat storage. IPostC reduced LDH and TXB2 in healthy and fatty livers and increased bile flow. LDH, TNF-\textgreeka, and IL-6 levels in serum decreased after warm ischemia + IPostC. The gene expressions of Tnf, IL-6, Ccl2, and Ripk3 were downregulated in vivo after IPostC. CONCLUSIONS IPostC showed protective effects after ischemia in situ and in vivo in healthy and fatty livers. Restricted cyclic inflow was an important mechanism and further suggested involvement of necroptosis. IPostC represents a promising and easy intervention to improve outcomes after transplantation.

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