title: Cytokine release and neutrophil activation are not prevented by heparin-coated circuits and aprotinin administration.
abstract: BACKGROUND
  Cardiopulmonary bypass (CPB) initiates a whole-body inflammatory response where complement and neutrophil activation and cytokine release play an important role. This prospective trial examined the effects of both heparin-coated circuits and aprotinin on the inflammatory processes during CPB, with respect to cytokine release and neutrophil activation.
  
  
  METHODS
  Two hundred patients undergoing cardiac surgery were randomized in four groups of 50 patients each: heparin-coated circuit with aprotinin (HCO-A) or without aprotinin (HCO) administration, and uncoated circuit with aprotinin (C-A) or without aprotinin administration (C). In groups receiving aprotinin, a high-dose regimen was given. In all groups, high initial doses of heparin were used (3 mg/kg intravenously). Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-8, and myeloperoxidase and elastase levels were measured in plasma samples taken before, during, and after CPB.
  
  
  RESULTS
  In all groups, the TNF-alpha, IL-6, and IL-8 levels reached a maximum after protamine administration. After 24 hours, they remained significantly elevated (IL-6 and IL-8) or returned to baseline values (TNF-alpha). A similar pattern was observed with myeloperoxidase and elastase levels. No significant intergroup differences were observed.
  
  
  CONCLUSIONS
  CPB is associated with cytokine release and neutrophil activation, which are not attenuated by the use of heparin-coated circuits or by the administration of aprotinin. Aprotinin and heparin-coated circuits do not show additive effects.
authors.affiliation: Department of Cardiovascular Surgery, University Hospital of Liège, Belgium. jo.defraigne@chu.ulg.ac.be
authors.forename: J O
authors.initials: JO
authors.lastname: Defraigne
authors.forename: J
authors.initials: J
authors.lastname: Pincemail
authors.forename: R
authors.initials: R
authors.lastname: Larbuisson
authors.forename: F
authors.initials: F
authors.lastname: Blaffart
authors.forename: R
authors.initials: R
authors.lastname: Limet
mesh_terms: D007611:Aprotinin / Q000627:therapeutic use; D002315:Cardiopulmonary Bypass; D020099:Coated Materials, Biocompatible; D016207:Cytokines / Q000097:blood*; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006490:Hemostatics / Q000627:therapeutic use; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D020099:Coated Materials, Biocompatible; D016207:Cytokines; D005343:Fibrinolytic Agents; D006490:Hemostatics; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D006493:Heparin; D007611:Aprotinin