title: Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non-heart-beating donors.
abstract: 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 °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.
  
  
  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-1β 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.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7065, USA.
authors.forename: Boming
authors.initials: B
authors.lastname: Dong
authors.forename: Paul W
authors.initials: PW
authors.lastname: Stewart
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Egan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000008:administration & dosage*; D006152:Cyclic GMP / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051550:I-kappa B Kinase / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D055370:Lung Injury / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016040:Lung Transplantation / Q000009:adverse effects; D008297:Male; D010477:Perfusion; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015427:Reperfusion Injury / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D012121:Respiration, Artificial / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D020858:Tissue and Organ Harvesting / Q000009:adverse effects / Q000379:methods*; D052096:Warm Ischemia; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D051550:I-kappa B Kinase; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D006152:Cyclic GMP