Abstract | OBJECTIVES: METHODS: Orthotopic left lung transplantation was performed in a syngenic Lewis-to-Lewis rat combination under 100% oxygen. Grafts were preserved in low- potassium dextran (LPD; Perfadex) at 4°C for 6 h with or without supplementation of 1 or 10 μM of BV into LPD. RESULTS: Prolonged cold storage and reperfusion resulted in a considerable deterioration of graft functions associated with massive apoptosis in the grafts after reperfusion. The untreated grafts exhibited the early up-regulations of mRNA for inflammatory mediators and an increase in a marker of lipid peroxidation, showing oxidative injuries. Although BV supplementation of LPD at a lower concentration (1 μM) did not improve the graft gas exchange, the grafts treated with BV (10 μM) showed a significant improvement of oxygenation and less inflammatory responses as well as reduced lipid peroxidation and apoptosis. Although the rapid activations of mitogen-activated protein kinases (MAPKs) were seen 30 min after reperfusion in the grafts stored in control LPD, BV treatment significantly reduced phosphorylated-MAPK protein expression. CONCLUSIONS: This study demonstrates that the exposure of the lung grafts to BV during cold storage can impart potent cytoprotective effects to lung cold ischaemia/ reperfusion injury and significantly improve the lung graft function following extended cold preservation and transplantation by the mechanism of a reduction in oxidative injury and following inflammatory events.
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Authors | Ryujiro Sugimoto, Yugo Tanaka, Kentaro Noda, Tomohiro Kawamura, Yoshiya Toyoda, Timothy R Billiar, Kenneth R McCurry, Atsunori Nakao |
Journal | European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
(Eur J Cardiothorac Surg)
Vol. 42
Issue 6
Pg. 1035-41
(Dec 2012)
ISSN: 1873-734X [Electronic] Germany |
PMID | 22648925
(Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Citrates
- Free Radical Scavengers
- Inflammation Mediators
- Organ Preservation Solutions
- Perfadex
- Biliverdine
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Topics |
- Animals
- Apoptosis
- Biliverdine
- Biomarkers
(metabolism)
- Blotting, Western
- Citrates
- Cold Ischemia
- Free Radical Scavengers
- Inflammation Mediators
(metabolism)
- Lung
(metabolism, pathology, physiology)
- Lung Transplantation
(methods)
- Male
- Organ Preservation
(methods)
- Organ Preservation Solutions
- Oxidative Stress
- Rats
- Rats, Inbred Lew
- Real-Time Polymerase Chain Reaction
- Reperfusion Injury
(metabolism, pathology, prevention & control)
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