title: Carbon monoxide can prevent acute lung injury observed after ischemia reperfusion of the lower extremities.
abstract: BACKGROUND
  Pulmonary expression of heme oxygenase has been observed in multiple studies. This expression has been found beneficial in decreasing the severity of acute lung injury (ALI) post ischemia-reperfusion (I/R). The aim of this study was to assess the role of exogenous administration of the end-products of heme oxygenase reaction, carbon monoxide, and bilirubin, in the severity of ALI.
  
  
  METHODS
  We compared five groups of rats (n = 7/group) including a sham group and four I/R of the lower extremities by clamping the abdominal aorta for 2 h followed by reperfusion for 2 h. The four I/R groups included a control group, one pretreated with bilirubin (50 micromol/kg IV), another with inhaled carbon monoxide (CO) (250 ppm), and the last pretreated with both. The severity of ALI has been evaluated by a histological assay grading neutrophilic infiltration, as well as a study of the microvascular permeability using the Evans blue.
  
  
  RESULTS
  The administration of CO prevented pulmonary microvascular permeability alteration noted after I/R of the lower limbs (pulmonary content of Evans blue: 141 +/- 23 microg/g of tissue in the isolated I/R group versus 68 +/- 34 microg/g of tissue in CO group; P < 0.001). Histologically CO administration inhibited neutrophilic sequestration observed after I/R. On the other hand, treatment by bilirubin alone (50 micromol/kg IV) did not modify the extent of pulmonary injury.
  
  
  CONCLUSIONS
  Exogenous administration of carbon monoxide by inhalation at low doses prevented ALI post-I/R in this model.
authors.affiliation: Laboratory of the Study of Cardiac Grafts and Protheses, Broussias Hospital, Paris, France. cherifboutros@hotmail.com
authors.forename: Cherif
authors.initials: C
authors.lastname: Boutros
authors.forename: Rachid
authors.initials: R
authors.lastname: Zegdi
authors.forename: Nermine
authors.initials: N
authors.lastname: Lila
authors.forename: Michele
authors.initials: M
authors.lastname: Cambillau
authors.forename: Paul
authors.initials: P
authors.lastname: Fornes
authors.forename: Alain
authors.initials: A
authors.lastname: Carpentier
authors.forename: Jean Noel
authors.initials: JN
authors.lastname: Fabini
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology*; D001663:Bilirubin / Q000494:pharmacology; D001794:Blood Pressure; D002248:Carbon Monoxide / Q000494:pharmacology*; D004396:Coloring Agents / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005070:Evans Blue / Q000493:pharmacokinetics; D006418:Heme / Q000378:metabolism; D006614:Hindlimb; D008297:Male; D011654:Pulmonary Edema / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D012720:Severity of Illness Index