title: Neutrophil elastase inhibitor improves survival rate after ischemia reperfusion injury caused by supravisceral aortic clamping in rats.
abstract: BACKGROUND
  Sivelestat sodium hydrate is a specific neutrophil elastase inhibitor effective in acute lung injury (ALI) associated with systemic inflammatory response syndrome. Bowel ischemia reperfusion injury (IRI) induced by supravisceral aortic clamping is associated with an excessive systemic inflammatory response, resulting in remote organ damage, including ALI. In this study, we investigated whether sivelestat can attenuate neutrophil sequestration in the lung, alleviate ALI, and improve survival in a rat bowel IRI model.
  
  
  METHODS
  Adult male Sprague-Dawley rats underwent bowel IRI induced by supravisceral aortic clamping and were randomly assigned to receive sivelestat or saline (control) and monitored for survival. We randomly assigned other rats to undergo laparotomy alone (sham operation), IRI alone, or IRI and sivelestat treatment. We evaluated blood samples for organ function, cytokine levels, and neutrophil elastase activity after reperfusion. Organs were analyzed histologically. We also determined lung injury in another set of rats.
  
  
  RESULTS
  Bowel IRI induced a significant increase in serum variables indicative of organ function, cytokine concentrations, neutrophil elastase activity, and lung permeability and edema, which reflected the presence of both systemic inflammatory response syndrome and compensatory anti-inflammatory response syndrome. Treatment with sivelestat significantly improved survival rate, lung permeability and edema, and significantly decreased levels of creatinine, interleukin 6, interleukin 10, and neutrophil elastase activity. Histological studies showed that sivelestat-treated rats had less bowel IRI-induced damage to lung and liver tissue than controls.
  
  
  CONCLUSIONS
  In a rat model, administration of sivelestat attenuated the effects of bowel IRI induced by supravisceral aortic clamping, and improved the survival rate.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Fujimura
authors.forename: Hideaki
authors.initials: H
authors.lastname: Obara
authors.forename: Koichi
authors.initials: K
authors.lastname: Suda
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Taku
authors.initials: T
authors.lastname: Miyasho
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Kawasako
authors.forename: Wenlin
authors.initials: W
authors.lastname: Du
authors.forename: Shingo
authors.initials: S
authors.lastname: Yamada
authors.forename: Shigeshi
authors.initials: S
authors.lastname: Ono
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Sachiko
authors.initials: S
authors.lastname: Matsuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yagi
authors.forename: Minoru
authors.initials: M
authors.lastname: Kitago
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shinoda
authors.forename: Osamu
authors.initials: O
authors.lastname: Itano
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanabe
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Ikuro
authors.initials: I
authors.lastname: Maruyama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000601:surgery*; D017544:Aortic Aneurysm, Abdominal / Q000601:surgery; D003250:Constriction; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007422:Intestines / Q000098:blood supply*; D008297:Male; D053491:Proteinase Inhibitory Proteins, Secretory / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; D015842:Serine Proteinase Inhibitors; D013449:Sulfonamides; C069195:sivelestat; D005998:Glycine