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J Thorac Cardiovasc Surg. 2013 Aug;146(2):429-36.e1. doi: 10.1016/j.jtcvs.2012.11.005. Epub 2012 Dec 20.

Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non-heart-beating donors.

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Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7065, USA.



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.


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 °C in an ex vivo lung perfusion circuit perfused with Steen solution. At 37 °C, lungs were ventilated for 15 minutes with alveolar gas with or without 500 ppm carbon monoxide, then perfusion-cooled to 20 °C, 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.


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-1β messenger RNA.


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.


11.4; 12; 38; 38.1; CO; DCD; ERK; EVLP; HO; IL; IRI; IκBα; JNK; LTX; MAPK; NF-κB; NHBD; NO; PA; TNF; c-Jun N-terminal kinase; cGMP; carbon monoxide; cyclic guanosine monophosphate; donation-after-cardiac-death donor; extracellular signal-regulated kinase; ex vivo lung perfusion; heme oxidase; iNOS; inducible nitric oxide synthase; interleukin; ischemia–reperfusion injury; lung transplantation; mRNA; messenger RNA; mitogen-activated protein kinase; nitrous oxide; non–heart-beating donor; nuclear factor kappa B; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; pulmonary artery; tumor necrosis factor

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