• Junichi Kohmoto, Atsunori Nakao, Takashi Kaizu, Allan Tsung, Atsushi Ikeda, Koji Tomiyama, Timothy R Billiar, Augustine M K Choi, Noriko Murase, and Kenneth R McCurry.
• Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
• Surgery. 2006 Aug 1; 140 (2): 179-85.

BackgroundCarbon monoxide (CO), a byproduct of heme catalysis by heme oxygenases, has been shown to provide protection against ischemia/reperfusion (I/R) injury. We examined the cytoprotective effect of CO at a low concentration on cold I/R injury of transplanted lung grafts.MethodsOrthotopic left lung transplantation was performed in syngenic Lewis to Lewis rat combination. Grafts were preserved in University of Wisconsin solution at 4 degrees C for 6 hours. Donors and/or recipients were exposed to CO (250 ppm) in air for 1 hour before surgery and then continuously post-transplantation.ResultsBlood oxygen partial pressure of graft pulmonary veins in the CO-treated group versus the air-treated group was significantly higher. The increase of messenger RNA of inflammatory mediators such as interleukin-6, tumor necrosis factor-alpha, inducible nitric oxide synthase, and cycloooxygenase-2 was markedly inhibited in the CO-treated group. The expression of phosphorylated-extracellular signal-regulated protein kinase 1/2 was significantly reduced in the CO-treated group. CO treatment reduced the number of infiltrating macrophages into the lung grafts. Vascular endothelial cells detected by CD31 stain were well preserved in CO-treated grafts, while those in air-treated grafts were faint and interrupted.ConclusionsThese results demonstrate that exogenous low-dose CO treatment of donors and recipients can prevent lung I/R injury and significantly improve function of lung grafts after extended cold preservation and transplantation.

18 keywords...

hide…