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J Thorac Cardiovasc Surg 2000;120:573-580
© 2000 The American Association for Thoracic Surgery

Cardiothoracic Transplantation

Inhibition of angiotensin-converting enzyme by captopril: A novel approach to reduce ischemia-reperfusion injury after lung transplantation

From the Thoracic Surgery Research Laboratory, Division of Thoracic Surgery, Toronto General Hospital Research Institute, University of Toronto, Toronto, Ontario, Canada.

Supported by grants from the National Sanitarium Association of Canada and the Canadian Cystic Fibrosis Foundation. M. Liu is a scholar of the Medical Research Council of Canada.

Address for reprints: Shaf Keshavjee, MD, Director, Toronto Lung Transplant Program, Division of Thoracic Surgery, Toronto General Hospital, 200 Elizabeth St, EN10-224, Toronto, Ontario, Canada, M5G 2C4 (E-mail: shaf.keshavjee{at}uhn.on.ca ).

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 free radical scavenger. The purpose of this study was to assess the protective effects of captopril against ischemia-reperfusion injury and to evaluate the ability of captopril to scavenge free radicals and inhibit neutrophil activation in an experimental model of lung transplantation.
Methods: A rat single-lung transplant model was used. Donor lungs were flushed and preserved in low-potassium dextran-glucose solution with (n = 5) and without captopril (500 µmol/L; n = 5) for 18 hours at 4°C and then transplanted and reperfused for 2 hours. At the conclusion of the 2-hour reperfusion period, arterial blood gases, blood pressure, and peak airway pressure were measured. Lung tissue biopsy specimens were obtained for assessment of wet/dry weight ratios, histology, and neutrophil sequestration (myeloperoxidase activity). Lipid peroxidation (F₂-isoprostane assay) was analyzed from plasma samples and tissue lysates.
Results: The addition of captopril to the lung preservation solution significantly improved postreperfusion PO ₂ (312 ± 63.3 mm Hg vs 202 ± 21.1 mm 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 F₂-isoprostane levels.
Conclusions: The use of captopril in the preservation solution ameliorates ischemia-reperfusion injury in transplanted lungs after an extended cold preservation period. The mechanisms by which captopril is protective remain elusive but do not appear to include inhibition of neutrophil sequestration or lipid peroxidation. This novel approach to ischemia-reperfusion injury may lead to improved lung function after transplantation and provide further insight into the pathogenesis of acute lung injury.

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