title: Attenuation of reperfusion-induced systemic inflammation by preconditioning with nitric oxide in an in situ porcine model of normothermic lung ischemia.
abstract: OBJECTIVE
  Inhalation of nitric oxide (NO) can ameliorate pulmonary ischemia/reperfusion (I/R) injury of the lung in several experimental models, but toxic effects of NO were also reported. Here we investigate whether NO inhalation for a short period prior to surgery is sufficient to prevent symptoms of lung I/R injury, especially the inflammatory response.
  
  
  METHODS
  Using an in situ porcine lung model, normothermic left lung ischemia was maintained for 90 min, followed by a 5-h reperfusion period (group 1, n = 7). In group 2 (n = 6), I/R was preceded by inhalation of NO (10 min, 15 ppm). Animals in group 3 (n = 7) underwent sham surgery without NO inhalation or ischemia.
  
  
  METHODS
  Oxygenation and hemodynamic parameters were measured as indicators of lung functional impairment. Plasma levels of interleukin (IL)-1beta, IL-6, and transforming growth factor (TGF)-beta1 were determined throughout the I/R maneuver. In addition, tissue macrophages were analyzed by lectin binding.
  
  
  RESULTS
  Symptoms of I/R injury (pulmonary hypertension and decreased oxygenation) in group 1 animals were attenuated by NO inhalation. The reperfusion-induced increases of the levels of IL-1beta and IL-6 in plasma were reduced by NO pretreatment. A peak of TGF-beta1 immediately after NO administration was observed in group 2, but not in groups 1 and 3. There was no significant effect of NO on tissue macrophages.
  
  
  CONCLUSIONS
  NO inhalation for a short period prior to lung I/R is sufficient to protect against pulmonary hypertension, impaired oxygenation, and the inflammatory response of pulmonary I/R injury.
authors.affiliation: Cardiovascular Institute, University Hospital Dresden, Dresden, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Waldow
authors.forename: Konstantin
authors.initials: K
authors.lastname: Alexiou
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Witt
authors.forename: Florian M
authors.initials: FM
authors.lastname: Wagner
authors.forename: Vassilios
authors.initials: V
authors.lastname: Gulielmos
authors.forename: Klaus
authors.initials: K
authors.lastname: Matschke
authors.forename: Michael
authors.initials: M
authors.lastname: Knaut
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D007511:Ischemia / Q000601:surgery*; D019194:Ischemic Preconditioning / Q000379:methods*; D008171:Lung Diseases / Q000601:surgery*; D008233:Lymphotoxin-alpha / Q000032:analysis; D009569:Nitric Oxide / Q000494:pharmacology*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D015424:Reperfusion / Q000009:adverse effects / Q000379:methods; D015427:Reperfusion Injury / Q000517:prevention & control*; D012680:Sensitivity and Specificity; D013552:Swine
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008233:Lymphotoxin-alpha; D009569:Nitric Oxide