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Combined Hypothermic and Normothermic Machine Perfusion Improves Functional Recovery of Extended Criteria Donor Livers.
Liver Transplantation 2018 July 31
BACKGROUND: Hypothermic oxygenated perfusion and normothermic perfusion are seen as distinct techniques of ex-situ machine perfusion of the liver. We aimed to demonstrate the feasibility of combining both techniques and whether it would improve functional parameters of donor livers into transplant standards.
METHODS: Ten discarded human donor livers had either 6 hours of normothermic perfusion (n=5) or 2 hours of hypothermic oxygenated perfusion followed by 4 hours of normothermic perfusion (n=5). Liver function was assessed according to our viability criteria; markers of tissue injury and hepatic metabolic activity were compared between groups.
RESULTS: Donor characteristics were comparable. During the hypothermic perfusion phase, livers down-regulated mitochondrial respiration (oxygen uptake, p=0.04; pCO2 perfusate, p=0.04) and increased ATP levels 1.77-fold. Following normothermic perfusion those organs achieved lower tissue expression of markers of oxidative injury (4-hydroxynonenal, p=0.008; CD14 expression, p=0.008) and inflammation (CD11b, p=0.02; vascular cell adhesion molecule 1, p=0.05) compared with livers that had normothermic perfusion alone. All livers in the combined group achieved viability criteria, whereas 40% (2/5) in the normothermic group failed (p=0.22).
CONCLUSION: This study suggests that a combined protocol of hypothermic oxygenated and normothermic perfusions might attenuate oxidative stress, tissue inflammation and improve metabolic recovery of the highest-risk donor livers compared to normothermic perfusion alone. This article is protected by copyright. All rights reserved.
METHODS: Ten discarded human donor livers had either 6 hours of normothermic perfusion (n=5) or 2 hours of hypothermic oxygenated perfusion followed by 4 hours of normothermic perfusion (n=5). Liver function was assessed according to our viability criteria; markers of tissue injury and hepatic metabolic activity were compared between groups.
RESULTS: Donor characteristics were comparable. During the hypothermic perfusion phase, livers down-regulated mitochondrial respiration (oxygen uptake, p=0.04; pCO2 perfusate, p=0.04) and increased ATP levels 1.77-fold. Following normothermic perfusion those organs achieved lower tissue expression of markers of oxidative injury (4-hydroxynonenal, p=0.008; CD14 expression, p=0.008) and inflammation (CD11b, p=0.02; vascular cell adhesion molecule 1, p=0.05) compared with livers that had normothermic perfusion alone. All livers in the combined group achieved viability criteria, whereas 40% (2/5) in the normothermic group failed (p=0.22).
CONCLUSION: This study suggests that a combined protocol of hypothermic oxygenated and normothermic perfusions might attenuate oxidative stress, tissue inflammation and improve metabolic recovery of the highest-risk donor livers compared to normothermic perfusion alone. This article is protected by copyright. All rights reserved.
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