Effect of the Selective NLRP3 Inflammasome Inhibitor mcc950 on Transplantation Outcome in a Pig Liver Transplantation Model with Organs from Donors after Cardiac Death Preserved by Hypothermic Machine Perfusion

Background We investigated whether the outcome of organs from donors after cardiac death (DCD) can be improved by the addition of mcc950 to the perfusate of the hypothermia machine perfusion (HMP) system and intravenous mcc950 injection after transplantation in a pig liver transplantation model. Methods Thirty-six healthy Bama mini pigs randomized into 3 groups. All the DCD livers were preserved in an HMP system after 2 h of simple cold storage (SCS).In HMP-Postop group, mcc950 was added to the perfusate; in the control group and Postop group, the perfusate was normal LPS. After transplantation, the pigs in the Postop group and HMP-Postop group were intravenously administered 3 mg/kg mcc950, at the time of reperfusion and on day 2 and day 3 after transplantation. During the 3-day follow-up period, general operative characteristics, and serological markers and histological features related to ischemia reperfusion injury were examined. Results The HMP-Postop group suffer the lightest ischemia reperfusion injury(IRI),and functioned best after transplantation. Model for the Early Allograft Function Score (MEAF, predictor of long-term survival), degree of injury in the hepatocytes and rate of apoptosis was lowest in the HMP-Postop group. Further, in the HMP-Postop group, the NLRP3 inflammasome pathway activation was lowest, and the level of IL-1β was lowest. Postop group functioned better than control group, but not comparable with HMP-Postop group. Conclusions The outcome of DCD organs can be improved by the addition of mcc950 to the perfusate of the HMP system and intravenous injection of mcc950 after transplantation. *Corresponding Author: Dr. Yong-Feng Liu, MD, First Affiliated Hospital, China Medical University, 155 Nanjing Street, Shenyang , Liaoning Province 110000, The People's Republic of China. E-mail: gdwkkyxx@sina.com AUTHORSHIP: Author's specific contributions: Yang Yu, Ying Cheng and Yong-Feng Liu designed the study, analyzed the data, interpreted the data and wrote the manuscript. Yang Yu, Qi Pan, Yi-Jie Zhang and De-Gong Jia, Ya performed the experiments, analyzed the data and participated in drafting the manuscript. Yang Yu and Qi Pan interpreted the data. Ying Cheng and Yong-Feng Liu contributed to the conception of the study, interpreted the data and revised the article critically. Disclosures: The authors have no conflicts of interest to declare. Funding: This study is funded by National natural science foundation of China (grant number :02046) and Basic Research on Key Laboratory of Liaoning Provincial Department of Education(grant number :LS201603) Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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