Propofol attenuates oxidant-induced acute lung injury in an isolated perfused rabbit-lung model.
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.
Yumoto
Masato
M
Department of Intensive Care, Toyota Medical Corperation Kariya General Hospital, 5-15 Sumiyoshi-chou, Kariya 448-8505, Japan.
Nishida
Osamu
O
Nakamura
Fujio
F
Katsuya
Hirotada
H
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
D000975:Antioxidants; D016877:Oxidants; D011687:Purines; D006861:Hydrogen Peroxide; D002374:Catalase; D014969:Xanthine Oxidase; C030985:purine; D015742:Propofol