Dataset Information

Hyperbaric oxygen therapy reduces the severity of ischaemia, preservation and reperfusion injury in a rat model of liver transplantation.

ABSTRACT:

Background

? Approaches to increase organ availability for orthotopic liver transplantation (OLT) often result in the procurement of marginal livers that are more susceptible to ischaemia, preservation and reperfusion injury (IPRI).

Methods

? The effects of post-OLT hyperbaric oxygen (HBO) therapy on IPRI in a syngeneic rat OLT model were examined at various time-points. The effects of IPRI and HBO on hepatocyte necrosis, apoptosis, proliferation, and sinusoidal morphology and ultrastructure were assessed.

Results

? Post-OLT HBO therapy significantly reduced the severity of IPRI; both apoptosis [at 12?h: 6.4 ± 0.4% in controls vs. 1.6 ± 0.7% in the HBO treatment group (p < 0.001); at 48?h: 2.4 ± 0.2% in controls vs. 0.4 ± 0.1% in the HBO treatment group (p < 0.001)] and necrosis [at 12?h: 18.7 ± 1.8% in controls vs. 2.4 ± 0.4% in the HBO treatment group (p < 0.001); at 48?h: 8.5 ± 1.3% in controls vs. 3.4 ± 0.9% in the HBO treatment group (P= 0.019)] were decreased. Serum alanine transaminase was reduced [at 12?h: 1068 ± 920?IU/l in controls vs. 370 ± 63?IU/l in the HBO treatment group (P= 0.030); at 48?h: 573 ± 261?IU/l in controls vs. 160 ± 10?IU/l in the HBO treatment group (P= 0.029)]. Treatment with HBO also promoted liver regeneration [proliferation at 12?h: 4.5 ± 0.1% in controls vs. 1.0 ± 0.3% in the HBO treatment group (p < 0.001); at 48?h: 8.6 ± 0.7% in controls vs. 2.9 ± 0.2% in the HBO treatment group (p < 0.01)] and improved sinusoidal diameter and microvascular density index.

Conclusions

? Hyperbaric oxygen therapy has persistent positive effects post-OLT that may potentially transfer into clinical practice.

SUBMITTER: Tran NQ

PROVIDER: S-EPMC3277052 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Publications

Hyperbaric oxygen therapy reduces the severity of ischaemia, preservation and reperfusion injury in a rat model of liver transplantation.

Tran Nhut Quang NQ Malcontenti-Wilson Caterina C Hammoud Soukena S Millar Ian I Christophi Chris C Muralidharan Vijayaragavan V

HPB : the official journal of the International Hepato Pancreato Biliary Association 20111113 2

<h4>Background</h4> Approaches to increase organ availability for orthotopic liver transplantation (OLT) often result in the procurement of marginal livers that are more susceptible to ischaemia, preservation and reperfusion injury (IPRI).<h4>Methods</h4> The effects of post-OLT hyperbaric oxygen (HBO) therapy on IPRI in a syngeneic rat OLT model were examined at various time-points. The effects of IPRI and HBO on hepatocyte necrosis, apoptosis, proliferation, and sinusoidal morphology and ult ...[more]

PMID: 22221571

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Project description:The lung is, more than other solid organs, susceptible for ischemia reperfusion injury after orthotopic transplantation. Corticosteroids are known to potently suppress pro-inflammatory processes when given in the post-operative setting or during rejection episodes. Whereas their use has been approved for these clinical indications, there is no study investigating its potential as a preservation additive in preventing vascular damage already in the phase of ischemia. To investigate these effects we performed orthotopic lung transplantations (LTX) in the rat. Prednisolone was either added to the perfusion solution for lung preservation or omitted and rats were followed for 48 hours after LTX. Prednisolone preconditioning significantly increased survival and diminished reperfusion edema. Hypoxia induced vasoactive cytokines such as VEGF were reduced. Markers of leukocyte invasiveness like matrix metalloprotease (MMP)-2, or common pro-inflammatory molecules like the CXCR4 receptor or the chemokine (C-C motif) ligand (CCL)-2 were downregulated by prednisolone. Neutrophil recruitment to the grafts was only increased in Perfadex treated lungs. Together with this, prednisolone treated animals displayed significantly reduced lung protein levels of neutrophil chemoattractants like CINC-1, CINC-2α/β and LIX and upregulated tissue inhibitor of matrix metalloproteinase (TIMP)-1. Interestingly, lung macrophage invasion was increased in both, Perfadex and prednisolone treated grafts, as measured by MMP-12 or RM4. Markers of anti-inflammatory macrophage transdifferentiation like MRC-1, IL-13, IL-4 and CD163, significantly correlated with prednisolone treatment. These observations lead to the conclusion that prednisolone as an additive to the perfusion solution protects from hypoxia triggered danger signals already in the phase of ischemia and thus reduces graft edema in the phase of reperfusion. Additionally, prednisolone preconditioning might also lead to macrophage polarization as a beneficial long-term effect.

Dataset Information

Hyperbaric oxygen therapy reduces the severity of ischaemia, preservation and reperfusion injury in a rat model of liver transplantation.

Background

Methods

Results

Conclusions

Publications

Hyperbaric oxygen therapy reduces the severity of ischaemia, preservation and reperfusion injury in a rat model of liver transplantation.

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