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

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.

• Authors: Yijie Zhang, Qi Pan, Ying Cheng, Yongfeng Liu
• Journal: European journal of medical research (Eur J Med Res) Vol. 26 Issue 1 Pg. 15 (Feb 05 2021) ISSN: 2047-783X [Electronic] England
• PMID: 33546770 (Publication Type: Journal Article)

Chemical References

• Anthracenes
• pyrazolanthrone

Topics

• Allografts (drug effects)
• Animals
• Anthracenes (pharmacology)
• Cold Temperature
• Death
• Disease Models, Animal
• Liver Transplantation
• Organ Preservation (methods)
• Perfusion (methods)
• Reperfusion Injury (prevention & control)
• Swine
• Swine, Miniature