Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation.
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...
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| Language: | English |
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Public Library of Science (PLoS)
2018-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5884561?pdf=render |
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| author | Zoltan Czigany Christian Bleilevens Christian Beckers Christian Stoppe Michaela Möhring Andras Fülöp Attila Szijarto Georg Lurje Ulf P Neumann René H Tolba |
| author_facet | Zoltan Czigany Christian Bleilevens Christian Beckers Christian Stoppe Michaela Möhring Andras Fülöp Attila Szijarto Georg Lurje Ulf P Neumann René H Tolba |
| author_sort | Zoltan Czigany |
| collection | DOAJ |
| description | 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).Male Lewis rats were used (n = 144 / 72 OLT cases; 240-340g) as donors and recipients. Livers were flushed and stored in 4°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.RIC 1 group showed significantly (p<0.05) improved portal venous and microcirculation flow as well as velocity. RIC has significantly reduced tissue injury according to the serum levels of transaminases and results of histopathological evaluation. Reduced TUNEL-staining (p<0.01 RIC 1-2 vs. Control) and elevated pBAD/BAD ratio was detected in the RIC groups (p<0.01 RIC 1 vs. Control). Supporting findings were obtained from measurements of serum IL-10 as well as tissue malondialdehyde and ATP levels. Hemoxygenase-1 (HO-1) mRNA-expression was significantly higher in RIC 1 compared to Control (p<0.05 RIC 1 vs. Control).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. |
| first_indexed | 2024-12-11T01:29:33Z |
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| id | doaj.art-f50494c4ebae4f979cab52831c19d34b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T01:29:33Z |
| publishDate | 2018-01-01 |
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| spelling | doaj.art-f50494c4ebae4f979cab52831c19d34b2022-12-22T01:25:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01134e019550710.1371/journal.pone.0195507Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation.Zoltan CziganyChristian BleilevensChristian BeckersChristian StoppeMichaela MöhringAndras FülöpAttila SzijartoGeorg LurjeUlf P NeumannRené H TolbaIschemic-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).Male Lewis rats were used (n = 144 / 72 OLT cases; 240-340g) as donors and recipients. Livers were flushed and stored in 4°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.RIC 1 group showed significantly (p<0.05) improved portal venous and microcirculation flow as well as velocity. RIC has significantly reduced tissue injury according to the serum levels of transaminases and results of histopathological evaluation. Reduced TUNEL-staining (p<0.01 RIC 1-2 vs. Control) and elevated pBAD/BAD ratio was detected in the RIC groups (p<0.01 RIC 1 vs. Control). Supporting findings were obtained from measurements of serum IL-10 as well as tissue malondialdehyde and ATP levels. Hemoxygenase-1 (HO-1) mRNA-expression was significantly higher in RIC 1 compared to Control (p<0.05 RIC 1 vs. Control).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.http://europepmc.org/articles/PMC5884561?pdf=render |
| spellingShingle | Zoltan Czigany Christian Bleilevens Christian Beckers Christian Stoppe Michaela Möhring Andras Fülöp Attila Szijarto Georg Lurje Ulf P Neumann René H Tolba Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation. PLoS ONE |
| title | Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation. |
| title_full | Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation. |
| title_fullStr | Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation. |
| title_full_unstemmed | Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation. |
| title_short | Limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation. |
| title_sort | limb remote ischemic conditioning of the recipient protects the liver in a rat model of arterialized orthotopic liver transplantation |
| url | http://europepmc.org/articles/PMC5884561?pdf=render |
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