1. Oxygenated hypothermic machine perfusion after static cold storage improves endothelial function of extended criteria donor livers.
- Author
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Burlage LC, Karimian N, Westerkamp AC, Visser N, Matton APM, van Rijn R, Adelmeijer J, Wiersema-Buist J, Gouw ASH, Lisman T, and Porte RJ
- Subjects
- Aged, Cell Survival, Donor Selection, Endothelial Cells pathology, Female, Gene Expression Regulation, Humans, Kruppel-Like Transcription Factors genetics, Kruppel-Like Transcription Factors metabolism, Liver metabolism, Liver pathology, Liver Transplantation adverse effects, Male, Middle Aged, Netherlands, Nitric Oxide metabolism, Nitric Oxide Synthase Type III genetics, Nitric Oxide Synthase Type III metabolism, Organ Preservation adverse effects, Organ Preservation instrumentation, Perfusion adverse effects, Perfusion instrumentation, RNA, Messenger genetics, RNA, Messenger metabolism, Thrombomodulin genetics, Thrombomodulin metabolism, Time Factors, Cold Temperature, Endothelial Cells metabolism, Hepatectomy adverse effects, Liver surgery, Liver Transplantation methods, Organ Preservation methods, Oxygen metabolism, Perfusion methods, Tissue Donors supply & distribution
- Abstract
Background: Lack of oxygen and biomechanical stimulation during static cold storage (SCS) of donor livers compromises endothelial cell function. We investigated the effect of end-ischemic oxygenated hypothermic machine perfusion (HMP) on endothelial cell function of extended criteria donor (ECD) livers., Methods: Eighteen livers, declined for transplantation, were transported to our center using static cold storage (SCS). After SCS, 6 livers underwent two hours of HMP, and subsequent normothermic machine perfusion (NMP) to assess viability. Twelve control livers underwent NMP immediately after SCS. mRNA expression of transcription factor Krüppel-like-factor 2 (KLF2), endothelial nitric oxide synthase (eNOS), and thrombomodulin (TM) was quantified by RT-PCR. Endothelial cell function and injury were assessed by nitric oxide (NO) production and release of TM into the perfusate., Results: In HMP livers, mRNA expression of KLF2 (p = 0.043), eNOS (p = 0.028), and TM (p = 0.028) increased significantly during NMP. In parallel, NO levels increased during NMP in HMP livers but not in controls. At the end of NMP cumulative TM release was significantly lower HMP livers, compared to controls (p = 0.028)., Conclusion: A short period of two hours oxygenated HMP restores endothelial cell viability after SCS and subsequent normothermic reoxygenation of ECD livers., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2017
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