title: Effects of methylprednisolone and a biocompatible copolymer circuit on blood activation during cardiopulmonary bypass.
abstract: BACKGROUND
  Cardiopulmonary bypass (CPB) induces derangements in physiology characterized by activation of blood pathways that may contribute to multiorgan dysfunction. This trial addresses the efficacy of a biocompatible surface alone and in combination with steroids in inhibiting these changes.
  
  
  METHODS
  In a factorial design, patients undergoing coronary artery bypass grafting were randomized (four groups; n = 17 per group) to CPB utilizing control circuits or a circuit prepared with a surface modifying active copolymer (SMA-CPB), with or without methylprednisolone (MPSS, 1 g intravenous). Leukocyte and complement activation, cytokine release, and bradykinin generation were measured. Clinical outcomes (blood loss, transfusion, arterial pressure response, and postoperative cardiac and pulmonary functions) were also examined.
  
  
  RESULTS
  The SMA-CPB was associated with a significant inhibition of elastase release (p = 0.026) and bradykinin generation (p = 0.027) during CPB. Terminal complement complex (TCC) generation was inhibited as an effect of SMA-CPB (p = 0.047). There was an interaction of SMA-CPB and MPSS to decrease both TCC (p = 0.042) and bradykinin generation (p = 0.028). There were strong effects of MPSS in inhibiting release of interleukin 6 (IL-6) (p = 0.007) and IL-8 (p < 0.001) and tissue plasminogen activator over time (p = 0.009) as well as decreasing peak day 1 creatine kinase (CK, p = 0.015) levels. Clinical effects of MPSS included decreased atrial fibrillation (p = 0.02), improved cardiac index over time, increased pulmonary compliance, and increased insulin need.
  
  
  CONCLUSIONS
  This trial suggests a potential beneficial effect for combined strategies to minimize inflammation after CPB. The specific effect of MPSS in decreasing postoperative atrial fibrillation and CK warrants further investigation of its role as a potential myocardial protective agent.
authors.affiliation: Division of Cardiac Surgery, University of Ottawa, Ottawa, Ontario, Canada. frubens@ottawaheart.ca
authors.forename: Fraser D
authors.initials: FD
authors.lastname: Rubens
authors.forename: Howard
authors.initials: H
authors.lastname: Nathan
authors.forename: Rosalind
authors.initials: R
authors.lastname: Labow
authors.forename: Kathryn S
authors.initials: KS
authors.lastname: Williams
authors.forename: Denise
authors.initials: D
authors.lastname: Wozny
authors.forename: Jacob
authors.initials: J
authors.lastname: Karsh
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
authors.forename: Thierry
authors.initials: T
authors.lastname: Mesana
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D001790:Blood Physiological Phenomena / Q000187:drug effects*; D001920:Bradykinin / Q000096:biosynthesis; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000295:instrumentation* / Q000379:methods; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003167:Complement Activation / Q000187:drug effects* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000209:etiology / Q000517:prevention & control; D010196:Pancreatic Elastase / Q000378:metabolism; D011108:Polymers / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D020099:Coated Materials, Biocompatible; D016207:Cytokines; D007378:Interleukins; D011108:Polymers; D010196:Pancreatic Elastase; D001920:Bradykinin; D008775:Methylprednisolone