Impact of Donor Age and Prolonged Warm Ischemia in Normothermic Machine Perfusion of Rat Livers
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The study "Impact of Donor Age and Prolonged Warm Ischemia in Normothermic Machine Perfusion of Rat Livers" published in Tissue Eng Part A investigated how donor age and circulatory death affect the viability of extended criteria donor (ECD) liver grafts using a rat normothermic machine perfusion (NMP) model. Livers from young (3-month) and older (12-month) rats were subjected to 30 minutes of warm ischemia followed by 3 or 6 hours of NMP. Functional parameters, metabolic markers, histology, and proteomics were analyzed.
Key findings include:
  • All grafts remained metabolically active, showing lactate clearance and bile production.
  • Older livers had more acidotic perfusate pH and increased necrosis after prolonged perfusion.
  • Younger livers exhibited higher transaminase release.
  • Proteomic analysis revealed age- and perfusion time-dependent changes in pathways related to mitochondrial damage, oxidative stress, and immune activation, which were not consistently detected by conventional viability markers.
The study suggests that histological and molecular assessments during NMP can better capture graft injury than standard markers, supporting tailored interventions to improve ECD graft quality and potentially expand their use in transplantation amidst organ shortages and an aging donor population.
Authors are A.S. Pietsch, L. Boerger, L. Padoan, K.A. Walter, J.M. Gassner, O. Klein O, L.A. Böhne, A. Arnold, D. Horst, I. Iske, K.H. Hillebrandt, F. Krenzien, J. Pratschke, I.M. Sauer, N. Raschzok, and S. Moosburner.
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