title: Propofol attenuates oxidant-induced acute lung injury in an isolated perfused rabbit-lung model.
abstract: OBJECTIVE
  Reactive oxygen species have been strongly implicated in the pathogenesis of acute lung injury (ALI). Some animal studies suggest that free radical scavengers inhibit the onset of oxidant-induced ALI. Propofol (2,6-diisopropylphenol) is chemically similar to phenol-based free radical scavengers such as the endogenous antioxidant vitamin E. Both in vivo and in vitro studies have suggested that propofol has antioxidant potential. We hypothesized that propofol may attenuate ALI by acting as a free-radical scavenger.
  
  
  METHODS
  We investigated the effects of propofol on oxidant-induced ALI induced by purine and xanthine oxidase (XO), in isolated perfused rabbit lung, in two series of experiments. In series 1, we examined the relationship between the severity of ALI and the presence of hydrogen peroxide (H2O2). In series 2, we evaluated the effects of propofol on attenuating ALI and the dose dependence of these effects. The lungs were perfused for 90 min, and we evaluated the effects on the severity of ALI by monitoring the pulmonary capillary filtration coefficient (Kfc), pulmonary arterial pressure (Ppa), and the pulmonary capillary hydrostatic pressure (Ppc).
  
  
  RESULTS
  In series 1, treatment with catalase (an H2O2 scavenger) prior to the addition of purine and XO resulted in complete prevention of ALI, suggesting that H2O2 may be involved closely in the pathogenesis of ALI. In series 2, pretreatment with propofol at concentrations in excess of 0.5 mM significantly inhibited the increases in the Kfc values, and that in excess of 0.75 mM significantly inhibited the increase in the Ppa values.
  
  
  CONCLUSIONS
  Propofol attenuates oxidant-induced ALI in an isolated perfused rabbit lung model, probably due to its antioxidant action.
authors.affiliation: Department of Intensive Care, Toyota Medical Corperation Kariya General Hospital, 5-15 Sumiyoshi-chou, Kariya 448-8505, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Yumoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishida
authors.forename: Fujio
authors.initials: F
authors.lastname: Nakamura
authors.forename: Hirotada
authors.initials: H
authors.lastname: Katsuya
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D016877:Oxidants; D010477:Perfusion; D015742:Propofol / Q000494:pharmacology*; D011687:Purines; D011817:Rabbits; D014969:Xanthine Oxidase
chemical_list: D000975:Antioxidants; D016877:Oxidants; D011687:Purines; D006861:Hydrogen Peroxide; D002374:Catalase; D014969:Xanthine Oxidase; C030985:purine; D015742:Propofol