Preservation solution supplemented with biliverdin prevents lung cold ischaemia/reperfusion injury

Ryujiro Sugimoto, Yugo Tanaka, Kentaro Noda, Tomohiro Kawamura, Yoshiya Toyoda, Timothy R. Billiar, Kenneth R. Mccurry, Atsunori Nakao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Objectives: Biliverdin (BV), one of the byproducts of heme catalysis through the heme oxygenase system, is a known scavenger of the reactive oxygen species. We hypothesized that adding BV to the perfusate and cold storage solution could protect rat lung grafts from oxidative injuries via its antioxidant efficacies. 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.

Original languageEnglish
Article numberezs298
Pages (from-to)1035-1041
Number of pages7
JournalEuropean Journal of Cardio-thoracic Surgery
Issue number6
StatePublished - Dec 2012
Externally publishedYes


  • Biliverdin
  • Cold preservation
  • Ischaemia reperfusion injury
  • Lung transplantation


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