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Published in: European Journal of Medical Research 1/2021

Open Access 01-12-2021 | Liver Transplantation | Research

Effects of SP600125 and hypothermic machine perfusion on livers donated after cardiac death in a pig allograft transplantation model

Authors: Yijie Zhang, Qi Pan, Ying Cheng, Yongfeng Liu

Published in: European Journal of Medical Research | Issue 1/2021

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Abstract

Background

Hypothermic machine perfusion (HMP) improves the quality of donor livers for transplantation, both in animal models and in clinical practice. Treatment with SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), can suppress the JNK signaling pathway to alleviate donor liver ischemia–reperfusion injury (IRI). We performed the present study with the objective of exploring the protective effects exerted by a combination of HMP and SP600125 on liver xenograft viability for donation after cardiac death (DCD) in a porcine model.

Methods

54 adult BAMA mini-pigs were randomly assigned to 5 groups, including sham, cold storage for 4 h (CS 4 h), CS 4 h + SP600125, CS 2 h + HMP 2 h, and CS 2 h + HMP 2 h + SP600125 groups. Donor livers in the CS 4 h and CS 4 h + SP600125 groups were conventionally cold preserved for 4 h, whereas donor livers in the CS 2 h + HMP 2 h and CS 2 h + HMP 2 h + SP600125 groups were cold preserved for 2 h and then treated with HMP for 2 h. The preservation and perfusion solutions contained SP600125 (20 µM). Follow-up was conducted for 5 days after liver transplantation to compare the surgical outcomes by means of serological examination, pathological results, and survival rate.

Results

The most satisfactory outcome after liver transplantation was observed in the CS 2 h + HMP 2 h + SP600125 group, which presented with minimal damage of donor livers during 5 days’ follow-up. Additionally, serological examination, pathological results, and survival rate concurred in showing better results in the CS 2 h + HMP 2 h ± SP600125 group than in the CS 4 h ± SP600125 group.

Conclusion

HMP in combination with SP600125 has hepatoprotective properties and improves the quality and viability of porcine livers collected after DCD, thus improving prognosis after liver transplantation.
Appendix
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Metadata
Title
Effects of SP600125 and hypothermic machine perfusion on livers donated after cardiac death in a pig allograft transplantation model
Authors
Yijie Zhang
Qi Pan
Ying Cheng
Yongfeng Liu
Publication date
01-12-2021
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2021
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-020-00472-9

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