title: Effect of a neutrophil elastase inhibitor on acute lung injury after cardiopulmonary bypass.
abstract: Cardiopulmonary bypass (CPB) has been implicated as a cause of acute lung injury (ALI) in cardiac surgical patients. We used a bronchoscopic microsampling (BMS) probe to examine alveolar biochemical constituents and evaluated the effect of sivelestat sodium hydrate, a novel synthesized polymorphonuclear (PMN) neutrophil elastase inhibitor, on ALI induced by CPB. Twelve patients undergoing aortic valve replacement were treated with either sivelestat 0.2 mg/kg/h (sivelestat group, n=6) or 0.9% saline (control group, n=6) from the start of surgery. Samples were collected by the BMS probe at three time points: after tracheal intubation, 1 h after CPB introduction, and 3 h after CPB termination. Pulmonary function was assessed perioperatively. There were no differences in baseline characteristics. The concentration of PMN elastase was significantly suppressed in the sivelestat group, compared with the control group (P=0.001). The sivelestat group also had lower levels of interleukin-6 and interleukin-8. Alveolar-arterial oxygen difference markedly increased, and a worsening of the PaO(2)/FiO(2) ratio indicated severe impairment after CPB. However, sivelestat attenuated the pattern of physiological deterioration of gas exchange. Sivelestat may attenuate neutrophil elastase or proinflammatory cytokines, and improve pulmonary dysfunction in patients undergoing CPB.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Nippon Medical School, Tokyo 113-8603, Japan. m-fujii@nms.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujii
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Bessho
authors.forename: Takashi
authors.initials: T
authors.lastname: Nitta
authors.forename: Masami
authors.initials: M
authors.lastname: Ochi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D055371:Acute Lung Injury / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001021:Aortic Valve / Q000601:surgery*; D018893:Bronchoalveolar Lavage / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D005260:Female; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019918:Heart Valve Prosthesis Implantation / Q000009:adverse effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D053491:Proteinase Inhibitory Proteins, Secretory / Q000008:administration & dosage / Q000627:therapeutic use*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D053491:Proteinase Inhibitory Proteins, Secretory; D013449:Sulfonamides; C069195:sivelestat; D019272:Leukocyte Elastase; D005998:Glycine