Carbon monoxide can prevent acute lung injury observed after ischemia reperfusion of the lower extremities.
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.
Boutros
Cherif
C
Laboratory of the Study of Cardiac Grafts and Protheses, Broussias Hospital, Paris, France. cherifboutros@hotmail.com
Zegdi
Rachid
R
Lila
Nermine
N
Cambillau
Michele
M
Fornes
Paul
P
Carpentier
Alain
A
Fabini
Jean Noel
JN
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