Carbon Monoxide Can Prevent Acute Lung Injury Observed After Ischemia Reperfusion of the Lower Extremities

BackgroundPulmonary 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.Study designWe 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 μmol/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.ResultsThe administration of CO prevented pulmonary microvascular permeability alteration noted after I/R of the lower limbs (pulmonary content of Evans blue: 141 ± 23 μg/g of tissue in the isolated I/R group versus 68 ± 34 μg/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 μmol/kg IV) did not modify the extent of pulmonary injury.ConclusionExogenous administration of carbon monoxide by inhalation at low doses prevented ALI post-I/R in this model.