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With the increasing number of patients waiting for liver transplantation, donor shortage has become a serious problem. The use of grafts from marginal donors and donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. The benefits of hypothermic oxygenated machine perfusion (HOPE) in many clinical trials have been reported. On the other hand, normothermic machine perfusion (NMP) has been also performed and demonstrated to improve graft function. The application of preservation solution with artificial oxygen carrier solution under subnormothermic machine perfusion for marginal liver graft was shown. Furthermore, long-term maintaining of graft function or recovery by NMP enables ex vivo cell and gene therapy. Thus, machine perfusion technology may alleviate the not only preservation of marginal graft but also new ex vivo bioengineering. [ABSTRACT FROM AUTHOR]

Introduction: The University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) are the most popular organ-preservative solutions. Ultrastructure of organelles reflects the functionality of cells, but less is understood about ultrastructural changes of hepatocytes after machine perfusion (MP) with HTK, than with UW solution. Methods: We evaluated the ultrastructure of hepatocytes preserved in HTK solution during hypothermic (4°C) and midthermic (22°C) MP (HMP and MMP, respectively) temperatures using osmium maceration scanning electron microscopy. Results: The functional ultrastructure of mitochondria in hepatocytes was maintained immediately after HMP and MMP. After 2 h in a porcine isolated liver reperfusion model (IRM) that simulates transplanted liver grafts, mitochondrial cristae became denser and some large vacuoles that we assumed were autophagosomes were detected in hepatocytes after HMP. Autophagy functions in the suppression of reactive oxygen generation and subsequent apoptosis, and these findings indicated that HMP is more effective than MMP when livers are preserved in HTK solution. Conclusion: The present findings contradict the previous findings of the UW solution that MMP is more effective than HMP. Thus, various combinations of conditions for MP should be carefully optimized before changing preservatives. [ABSTRACT FROM AUTHOR]