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Objective
We sought to determine whether ventilation of lungs after death in non-
heart-
beating donors with carbon monoxide during warm ischemia and ex vivo lung perfusion and after transplant would reduce ischemia-reperfusion injury and improve lung function.
Methods
One hour after death, Sprague-Dawley rats were ventilated for another hour with 60 % oxygen (control group) or 500 ppm carbon monoxide in 60 % oxygen (CO-vent group; n=6/group). Then, lungs were flushed with 20 mL cold Perfadex, stored cold for 1 hour, then warmed to 37¡ãC in an ex vivo lung perfusion circuit perfused with Steen solution. At 37¡ãC, lungs were ventilated for 15 minutes with alveolar gas with or without 500 ppm carbon monoxide, then perfusion-cooled to 20¡ãC, flushed with cold Perfadex and stored cold for 2?hours. The left lung was transplanted using a modified cuff technique. Recipients were ventilated with 60 % oxygen with or without carbon monoxide. One hour after transplant, we measured blood gases from the left pulmonary vein and aorta, and wet-to-dry ratio of both lungs. The RNA and protein extracted from graft lungs underwent real-time polymerase chain reaction and Western blotting, and measurement of cyclic guanosine monophosphate by enzyme-linked immunosorbent assay.
Results
Carbon monoxide ventilation begun 1 hour after death reduced wet/dry ratio after ex vivo lung perfusion. After transplantation, the carbon monoxide-ventilation group had better oxygenation; higher levels of tissue cyclic guanosine monophosphate, heme oxidase-1 expression, and p38 phosphorylation; reduced c-Jun N-terminal kinase phosphorylation; and reduced expression of interleukin-6 and interleukin-1¦Â messenger RNA.
Conclusions
Administration of carbon monoxide to the deceased donor and non-heart-beating donor lungs reduces ischemia-reperfusion injury in rat lungs transplanted from non-heart-beating donors. Therapy to the deceased donor via the airway may improve post-transplant lung function.
