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Addition of a neutrophil elastase inhibitor to the organ flushing solution decreases lung reperfusion injury in rat lung transplantation

Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama City, Japan

Received 7 March 2007; received in revised form 7 July 2007; accepted 11 July 2007.

^_* Corresponding author. Address: Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikatacho, Okayama Prefecture, Okayama City 700-8558, Japan. Tel.: +81 86 235 7265; fax: +81 86 235 7269. (Email: hmori-ths{at}umin.ac.jp).

Background: Neutrophil elastase plays an important role in ischemia–reperfusion injury. We hypothesized that the addition of sivelestat, a specific neutrophil elastase inhibitor, to the organ flushing solution would decrease reperfusion injury in a rat single left-lung transplant model. Methods: All donor lungs were flushed with 25 ml low-potassium dextran–glucose solution and stored for 16 h at 4 °C. Rats were divided into three experimental groups (n = 10) that received donor lungs washed in either normal flushing solution (group 1), or flushing solution containing 20 mg sivelestat (group 2) or 40 mg sivelestat (group 3). Graft function was assessed 48 h after reperfusion using five measurements: isolated graft oxygenation, wet/dry ratio, peak airway pressure, tissue myeloperoxidase activity, and serum lipid peroxides level. Histological examination of lung grafts was also performed. Results: Group 3 showed better oxygenation (groups 1, 2, and 3: 133.9 ± 113.5, 254.0 ± 84.6, and 378.7 ± 77.6 mmHg, respectively; p < 0.0001 vs group 1, p = 0.0052 vs group 2), lower peak airway pressure (groups 1, 2, and 3: 28.7 ± 6.1, 26.0 ± 5.8, and 21.5 ± 5.3 mmHg, respectively; p = 0.0385 vs group 1), lower wet/dry ratio (groups 1, 2, and 3: 6.74 ± 0.78, 5.77 ± 0.52, and 4.90 ± 0.16, respectively; p = 0.0010 vs group 1), and lower myeloperoxidase activity (groups 1, 2, and 3: 0.304 ± 0.081, 0.178 ± 0.053, and 0.106 ± 0.029 OD/mg/min, respectively; p < 0.0001 vs group 1, p = 0.0319 vs group 2). No significant differences in arterial PaCO₂ and serum lipid peroxide levels were observed between the three groups. Conclusions: Addition of sivelestat to the organ flushing solution ameliorated ischemia–reperfusion injury in a lung transplant model.

Key Words: Ischemia/reperfusion • Leukocytes • Lung transplantation

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