Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation

Zoltan Czigany*, Christian Bleilevens, Christian Beckers, Christian Stoppe, Michaela Moehring, Andras Fueloep, Attila Szijarto, Georg Lurje, Ulf P. Neumann, Rene H. Tolba

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background

Ischemic-reperfusion (IR) injury still represents a major concern in clinical transplantation, especially in the era of extreme organ shortage and extended criteria donor organs. In the present study we aimed to investigate the hepatoprotective effects of remote ischemic conditioning (RIC) in a rat model of arterialized orthotopic liver transplantation (OLT).

Methods

Male Lewis rats were used (n = 144 / 72 OLT cases; 240-340g) as donors and recipients. Livers were flushed and stored in 4 degrees C HTK-solution for 8h before implantation. Recipients were randomly allocated into three experimental groups: RIC 1, RIC 2, Control. In RIC 1, RIC 2 groups, RIC was applied in the recipient before hepatectomy or after reperfusion (4x5-5min IR via clamping the infrarenal aorta), respectively. Animals were sacrificed at 1, 3,24,168h post-reperfusion (n = 6 recipient/group/time point). Hepatocellular injury, graft circulation, serum cytokines, tissue redox-stress and adenosine-triphosphate (ATP) levels have been assessed. Additional markers were analyzed, using Western blotting and reverse-transcription polymerase chain reaction.

Results

RIC 1 group showed significantly (p

Conclusion

These results suggest that RIC might confer potent protection against the detrimental effects of IR injury including tissue damage, apoptosis, graft circulation, inflammation, tissue energetic status in OLT. HO-1 overexpression might play an orchestrating role in RIC mediated organ protection. An earlier intervention (RIC 1 protocol) was more effective than remote conditioning after graft reperfusion.

Original languageEnglish
Article number0195507
Number of pages21
JournalPLOS ONE
Volume13
Issue number4
DOIs
Publication statusPublished - 4 Apr 2018

Keywords

  • REPERFUSION INJURY
  • ISCHEMIA/REPERFUSION INJURY
  • MICROCIRCULATION
  • PRESERVATION
  • MECHANISMS
  • GRAFTS
  • CARDIOPROTECTION
  • PRETREATMENT
  • PROTOCOLS
  • APOPTOSIS

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