title: Induction of acute-phase reactive substances during open-heart surgery and efficacy of ulinastatin. Inhibiting cytokines and postoperative organ injury.
abstract: OBJECTIVE
  A systemic inflammatory response after open-heart surgery using cardiopulmonary bypass may be responsible for postoperative organ dysfunction. Ulinastatin, a protease inhibitor, plays an important role in host defense under periods of stress.
  
  
  METHODS
  We studied the efficacy of ulinastatin on changes in acute-phase reactive substances during and after open-heart surgery. Patients undergoing open-heart surgery were divided into an ulinastatin group (Group U) and a control group (Group C). In Group U, we introduced 600,000 units of ulinastatin into a priming solution for cardiopulmonary bypass, 300,000 units into a cardiopulmonary bypass circuit at the removal of aortic cross-clamping, and 300,000 units a day for 5 days following surgery.
  
  
  RESULTS
  Immediately after cardiopulmonary bypass, alpha 1-antitrypsin levels decreased significantly in both groups, and increased significantly on the second day after surgery. Ulinastatin levels decreased after cardiopulmonary bypass in Group C. Significantly high levels of ulinastatin were obtained in Group U. Interleukin-6, interleukin-8, and polymorphonuclear elastase were markedly induced, and high levels of plasma concentration continued for several days after surgery. At all sample points, these concentrations in Group U tended to be lower than those in Group C. A significantly positive correlation was seen between the maximum levels of interleukin-8 and polymorphonuclear elastase, but these cytokine and polymorphonuclear elastase levels did not correlate with parameters such as the duration of anesthesia, surgery, cardiopulmonary bypass, or aortic cross-clamping.
  
  
  CONCLUSIONS
  Our study suggests that high-dose ulinastatin administration to maintain a sufficient concentration of circulating protease inhibitors may suppress overinduction of cytokines and polymorphonuclear elastase in open-heart surgery.
authors.affiliation: Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Ishikawa
authors.forename: A
authors.initials: A
authors.lastname: Otaki
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Yamagishi
authors.forename: Y
authors.initials: Y
authors.lastname: Morishita
mesh_terms: D000368:Aged; D006348:Cardiac Surgical Procedures; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000627:therapeutic use*; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D008297:Male; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000097:blood; D011183:Postoperative Complications / Q000517:prevention & control; D011480:Protease Inhibitors / Q000097:blood*; D014361:Trypsin Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D006023:Glycoproteins; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D010196:Pancreatic Elastase; C028665:urinastatin