The effects of a specific neutrophil elastase inhibitor (ONO-5046) in pulmonary ischemia–reperfusion injury |
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Authors: | Norihiko Ishikawa Makoto Oda Masahiko Kawaguchi Yoshio Tsunezuka Go Watanabe |
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Affiliation: | Department of General and Cardiothoracic Surgery, School of Medicine, Kanazawa University, 13-1 Takara-machi, 920-8640 Kanazawa, Japan. nori-i@csc.ne.jp |
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Abstract: | Ischemia-reperfusion injury is a significant problem in lung transplantation. Polymorphonuclear elastase derived from neutrophils plays a major mechanistic role in this process. Hence, we have investigated the effects of ONO-5046, a neutrophil elastase inhibitor, on ischemia-reperfusion injury. Fifteen rabbits were divided into three groups: 2 h of single left-lung perfusion (control group, n=3); 2 h of ischemia followed by 2 h of reperfusion (ischemic group, n=6); and drip intravenous administration of ONO-5046 during the 2 h of ischemia and 2 h of reperfusion (ONO-5046 group, n=6). Hemodynamic parameters were determined and a histopathological examination of the lung was performed. In the ONO-5046 group, arterial oxygen pressure, cardiac output, and tissue blood perfusion were higher and pulmonary vascular resistance was lower than in the ischemic group. The ONO-5046 group also showed large decreases in neutrophil infiltration, pulmonary edema, and intra-alveolar hemorrhage. Treatment with ONO-5046 improves lung function in a rabbit-lung ischemia-reperfusion model. |
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Keywords: | Ischemia—reperfusion injury Polymorphonuclear elastase Lung transplantation Neutrophil infiltration Specific neutrophil elastase inhibitor |
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