title: Neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury after cardiopulmonary bypass in the rabbit endotoxemia model.
abstract: BACKGROUND
  Neutrophil elastase probably contributes to the development of acute lung injury after cardiopulmonary bypass (CPB) in patients with infection or shock. We evaluated whether pretreatment with sivelestat sodium hydrate, a neutrophil elastase inhibitor (EI), can prevent acute lung injury caused by CPB.
  
  
  METHODS
  Rabbits were assigned four groups: CPB for 60 minutes, control CPB group; low-dose lipopolysaccharide (LPS) administration without CPB, LPS group; CPB after lipopolysaccharide administration, LPS+CPB group; or preparation with continuous infusion of sivelestat and CPBs after lipopolysaccharide administration, EI group. Blood samples to determine blood gas concentration, plasma elastase activity, and plasma interleukin-8 levels were obtained. Histopathologic examinations of the lung were performed.
  
  
  RESULTS
  The decreased arterial oxygen pressure at the end of CPB was observed in the LPS+CPB group only, but was suppressed in the EI group (p < 0.01). Elastase activity was markedly elevated at 120 minutes after CPB, and interleukin-8 levels were markedly elevated at 180 minutes in the LPS+CPB group but were much lower (p < 0.05) in the EI group. Histopathology demonstrated accumulation of polymorphonuclear neutrophils in bronchoalveolar areas in the LPS+CPB group (p < 0.01). Pulmonary myeloperoxidase activity was significantly lower in the LPS+CPB group than in the other groups (p < 0.01). These changes were minimal in the EI group.
  
  
  CONCLUSIONS
  The combination of low dose LPS+60 minutes of CPB, but neither intervention alone, produced evidence of acute lung injury in a rabbit model. This did not occur when the animals were pretreated with sivelestat.
authors.affiliation: First Department of Surgery, Hirosaki University School of Medicine, Aomori, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Wakayama
authors.forename: Ikuo
authors.initials: I
authors.lastname: Fukuda
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016209:Interleukin-8 / Q000097:blood; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity*; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D012128:Respiratory Distress Syndrome / Q000517:prevention & control*; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D016209:Interleukin-8; D008070:Lipopolysaccharides; D013449:Sulfonamides; C069195:sivelestat; D009195:Peroxidase; D019272:Leukocyte Elastase; D005998:Glycine