title: High-dose nitric oxide inhalation increases lung injury after gastric aspiration.
abstract: BACKGROUND
  Inhaled nitric oxide is often used in patients with adult respiratory distress syndrome. However, nitric oxide also may be significantly toxic, especially if administered concurrently with hyperoxia. The authors evaluated the isolated effect of nitric oxide and the combined effects of nitric oxide and hyperoxia on lung injury in rats after acid aspiration.
  
  
  METHODS
  Animals were injured by instillation of 1.2 ml/kg hydrogen chloride in low-pH saline (the acid group) or acidified gastric particles (the casp group) into the lungs under halothane anesthesia via a tracheal catheter. Controls received no injury vehicle but rather underwent the surgical process. After recovery from anesthesia, the animals were exposed to 20% or 90% oxygen with or without 20, 40, or 80 ppm nitric oxide for 5 h. The permeability index, alveolar-arterial oxygen difference, the ratio of oxygen pressure to the inspired fraction of oxygen, and the ratio of wet to dry weight were assessed 5 h after injury as indices of lung injury. Data were assessed using analysis of variance.
  
  
  RESULTS
  Each group included 6-10 rats. Exposure to nitric oxide (80 ppm) in air increased protein permeability in the lungs to a permeability index of 1.42+/-0.12 after acid aspiration. The combination of nitric oxide (80 ppm) and hyperoxia further increased protein leakage to a permeability index of 2.1+/-0.25. Exposure to lower concentrations of nitric oxide (e.g., 20 and 40 ppm) increased the permeability index of the lungs (1.44+/-0.21, 1.75+/-0.29, respectively) in the presence of hyperoxia, although it did not affect the permeability index of the lungs during exposure to air. Pretreatment of animals with deferoxamine and methylene blue partially inhibited the adverse effect of hyperoxia and nitric oxide, which suggested a complex underlying mechanism involving both reactive-species generation and pulmonary vasomotor changes.
  
  
  CONCLUSIONS
  These results show that inhaled nitric oxide at 80 ppm for a short duration (5 h) increases the severity of the inflammatory microvascular lung injury after acid aspiration. The pulmonary damage is exacerbated further in the presence of high oxygen concentrations. Although lower concentrations of nitric oxide did not increase the extent of lung injury, longer exposure times need to be assessed.
authors.affiliation: Department of Anesthesiology, State University of New York at Buffalo, USA. nnaderdj@acsu.buffalo.edu
authors.forename: N D
authors.initials: ND
authors.lastname: Nader
authors.forename: P R
authors.initials: PR
authors.lastname: Knight
authors.forename: I
authors.initials: I
authors.lastname: Bobela
authors.forename: B A
authors.initials: BA
authors.lastname: Davidson
authors.forename: K J
authors.initials: KJ
authors.lastname: Johnson
authors.forename: F
authors.initials: F
authors.lastname: Morin
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000633:toxicity*; D010100:Oxygen / Q000633:toxicity; D010539:Permeability; D011015:Pneumonia, Aspiration / Q000150:complications*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D011506:Proteins; D009569:Nitric Oxide; D010100:Oxygen; D008751:Methylene Blue