Inhibition of angiotensin-converting enzyme by captopril: A novel approachto reduce ischemia-reperfusion injury after long transplantation

Objectives: Ischemia-reperfusion injury after lung transplantation involves the generation of free radicals. Captopril has been shown to be protective in models of ischemia-reperfusion injury in other organs by acting as a fr ee radical scavenger. The purpose of this study was to assess the protectiv e effects of captopril against ischemia-reperfusion injury and to evaluate the ability of captopril to scavenge free radicals and inhibit neutrophil a ctivation in an experimental model of lung transplantation. Methods: A rat single-lung transplant mode! was used. Donor lungs were flus hed and preserved in low-potassium dextran-glucose solution with (n = 5) an d without captopril (500 mu mol/L; n = 5) for 18 hours at 4 degrees C and t hen transplanted and reperfused for 2 hours. At the conclusion of the 2-hou r reperfusion period, arterial blood gases, blood pressure, and peak airway pressure were measured. Lung tissue biopsy specimens were obtained for ass essment of wet/dry weight ratios, histology, and neutrophil sequestration ( myeloperoxidase activity). Lipid peroxidation (F-2-isoprostane assay) was a nalyzed from plasma samples and tissue lysates. Results: The addition of captopril to the lung preservation solution signif icantly improved postreperfusion P-O2 (312 +/- 63.3 mm Hg vs 202 +/- 21.1 m m Hg; P = .006), peak airway pressure (11.4 +/- 1.1 cm H2O vs 15.6 +/- 1.5 cm H2O; P = .001), and wet/dry weight ratio (4.9 +/- 0.4 vs 15.8 +/- 10.9; P = .008). Blood pressures did not differ significantly between groups. No significant differences were seen in myeloperoxidase activity or F-2-isopro stane levels. Conclusions: The use of captopril in the preservation solution ameliorates ischemia-reperfusion injury in transplanted lungs after an extended cold pr eservation period. The mechanisms by which captopril is protective remain e lusive but do not appear to include inhibition of neutrophil sequestration or lipid peroxidation. This novel approach to ischemia-reperfusion injury m ay lead to improved lung function after transplantation and provide further insight into the pathogenesis of acute lung injury.