title: Hypercapnic acidosis attenuates reperfusion injury in isolated and perfused rat lungs.
abstract: OBJECTIVE
  Although ischemia-reperfusion injury is a major determinant of primary graft dysfunction after lung transplantation, an approach to extend preoperative lung preservation to postoperative protection has not yet been defined. The purpose of this study was to determine the protective effects of and the signal pathway regulated by hypercapnic acidosis in ischemia-reperfusion-induced lung injury.
  
  
  METHODS
  Animal study.
  
  
  METHODS
  Animal care facility procedure room in a medical center.
  
  
  METHODS
  Adult male Sprague-Dawley rats.
  
  
  METHODS
  Lung injury was induced in a clinically relevant ex vivo animal model. Animals were divided into a control group (FICO(2), 5%; n = 6), ischemia-reperfusion group (FICO(2), 5%; n = 6), and hypercapnic acidosis (ischemia-reperfusion + hypercapnic acidosis) group (FICO(2), 10%; n = 6).
  
  
  RESULTS
  Ischemia-reperfusion caused significant increases in alveolar lavage and perfusate tumor necrosis factor-α, inflammatory cell infiltration, lung tissue malondialdehyde, bronchoalveolar lavage fluid protein concentration and lactate dehydrogenase activity, lung weight gain, and infiltration coefficient. Ventilation with 10% CO(2) significantly suppressed the inflammatory response and attenuated lung ischemia-reperfusion injury. Our results also showed that hypercapnic acidosis significantly inhibited the ischemia-reperfusion-induced phosphorylation and nuclear translocation of nuclear factor-κB. This was associated with elevation of inhibitor of nuclear factor-κB-α level and reduced IκB kinase-β phosphorylation, suggesting a suppression of IκB kinase and thus IκB-α activation.
  
  
  CONCLUSIONS
  Hypercapnic acidosis may attenuate lung ischemia-reperfusion injury by suppressing the activation of the IκB kinase-nuclear factor-κB pathway.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Wu
authors.forename: Chin-Pyng
authors.initials: CP
authors.lastname: Wu
authors.forename: Bor-Hwang
authors.initials: BH
authors.lastname: Kang
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Li
authors.forename: Shi-Jye
authors.initials: SJ
authors.lastname: Chu
authors.forename: Kun-Lun
authors.initials: KL
authors.lastname: Huang
mesh_terms: D000142:Acidosis, Respiratory; D055371:Acute Lung Injury / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015151:Immunoblotting; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D012307:Risk Factors; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase