title: Carbon monoxide inhalation reduces pulmonary inflammatory response during cardiopulmonary bypass in pigs.
abstract: BACKGROUND
  Cardiopulmonary bypass (CPB) is associated with pulmonary inflammation and dysfunction. This may lead to acute lung injury and acute respiratory distress syndrome with increased morbidity and mortality. The authors hypothesized that inhaled carbon monoxide before initiation of CPB would reduce inflammatory response in the lungs.
  
  
  METHODS
  In a porcine model, a beating-heart CPB was used. The animals were either randomized to a control group, to standard CPB, or to CPB plus carbon monoxide. In the latter group, lungs were ventilated with 250 ppm inhaled carbon monoxide in addition to standard ventilation before CPB. Lung tissue samples were obtained at various time points, and pulmonary cytokine levels were determined.
  
  
  RESULTS
  Hemodynamic parameters were largely unaffected by CPB or carbon monoxide inhalation. There were no significant differences in cytokine expression in mononuclear cells between the groups throughout the experimental time course. Compared with standard CPB animals, carbon monoxide significantly suppresses tumor necrosis factor-alpha and interleukin-1beta levels (P < 0.05) and induced the antiinflammatory cytokine interleukin 10 (P < 0.001). Carbon monoxide inhalation modulates effector caspase activity in lung tissue during CPB.
  
  
  CONCLUSIONS
  The results demonstrate that inhaled carbon monoxide significantly reduces CPB-induced inflammation via suppression of tumor necrosis factor alpha, and interleukin-1beta expression and elevation of interleukin 10. Apoptosis induced by CPB was associated with caspase-3 activation and was significantly attenuated by carbon monoxide treatment. Based on the observations of this study, inhaled carbon monoxide could represent a potential new therapeutic modality for counteracting CPB-induced lung injury.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University Medical Center Freiburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Goebel
authors.forename: Matthias
authors.initials: M
authors.lastname: Siepe
authors.forename: Anne
authors.initials: A
authors.lastname: Mecklenburg
authors.forename: Phillip
authors.initials: P
authors.lastname: Stein
authors.forename: Martin
authors.initials: M
authors.lastname: Roesslein
authors.forename: Christian I
authors.initials: CI
authors.lastname: Schwer
authors.forename: Rene
authors.initials: R
authors.lastname: Schmidt
authors.forename: Torsten
authors.initials: T
authors.lastname: Doenst
authors.forename: Klaus K
authors.initials: KK
authors.lastname: Geiger
authors.forename: Heike L
authors.initials: HL
authors.lastname: Pahl
authors.forename: Christian
authors.initials: C
authors.lastname: Schlensak
authors.forename: Torsten
authors.initials: T
authors.lastname: Loop
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001784:Blood Gas Analysis; D015152:Blotting, Northern; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000494:pharmacology*; D002263:Carboxyhemoglobin / Q000032:analysis / Q000378:metabolism; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D053148:Caspase 3 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control*; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D023421:Models, Animal; D010100:Oxygen / Q000097:blood; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000963:Antimetabolites; D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D053148:Caspase 3; D010100:Oxygen