The effects of a specific neutrophil elastase inhibitor (ONO-5046) in pulmonary ischemia-reperfusion injury.
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.
Ishikawa
Norihiko
N
Department of General and Cardiothoracic Surgery, School of Medicine, Kanazawa University, 13-1 Takara-machi, 920-8640 Kanazawa, Japan. nori-i@csc.ne.jp
Oda
Makoto
M
Kawaguchi
Masahiko
M
Tsunezuka
Yoshio
Y
Watanabe
Go
G
D000818:Animals; D002302:Cardiac Output; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008171:Lung Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016040:Lung Transplantation; D010100:Oxygen / Q000097:blood; D011652:Pulmonary Circulation; D011669:Pulmonary Wedge Pressure; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D014655:Vascular Resistance
D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D010100:Oxygen; D005998:Glycine