title: Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves C-reactive protein and is associated with postoperative arrhythmia.
abstract: BACKGROUND
  Complement activation during cardiopulmonary bypass (CPB) surgery is considered to result from interaction of blood with the extracorporeal circuit. We investigated whether additional mechanisms may contribute to complement activation during and after CPB and, in particular, focused on a possible role of the acute-phase protein C-reactive protein (CRP).
  
  
  RESULTS
  In 19 patients enrolled for myocardial revascularization, perioperative and postoperative levels of complement activation products, interleukin-6 (IL-6), CRP, and complement-CRP complexes, reflecting CRP-mediated complement activation in vivo, were measured and related to clinical symptoms. A biphasic activation of complement was observed. The ratio between the areas under the curve of perioperative and postoperative C3b/c and C4b/c were 3:2 and 1:46, respectively. IL-6 levels reached a maximum at 6 hours post-surgery. CRP levels peaked on the second postoperative day. Each complement-CRP complex had peak levels on the second or third postoperative day. By multivariate analysis, maximum levels of CRP on the second postoperative day were mainly explained by C4b/c levels after protamine administration, leukocyte count on the second postoperative day, and preoperative levels of CRP. Peak levels of C4b/c after protamine administration (P=.0073) and on the second postoperative day correlated with the occurrence of arrhythmia on the same day (P=.0065).
  
  
  CONCLUSIONS
  Cardiac surgery with CPB causes a biphasic complement activation. The first phase occurs during CPB and results from the interaction of blood with the extracorporeal circuit. The second phase, which occurs during the first 5 days after surgery, involves CRP, is related to baseline CRP levels, and is associated with clinical symptoms such as arrhythmia.
authors.affiliation: Department of Anaesthesiology, Academic Medical Centre, Amsterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Bruins
authors.forename: H
authors.initials: H
authors.lastname: te Velthuis
authors.forename: A P
authors.initials: AP
authors.lastname: Yazdanbakhsh
authors.forename: P G
authors.initials: PG
authors.lastname: Jansen
authors.forename: F W
authors.initials: FW
authors.lastname: van Hardevelt
authors.forename: E M
authors.initials: EM
authors.lastname: de Beaumont
authors.forename: C R
authors.initials: CR
authors.lastname: Wildevuur
authors.forename: L
authors.initials: L
authors.lastname: Eijsman
authors.forename: A
authors.initials: A
authors.lastname: Trouwborst
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
mesh_terms: D000210:Acute-Phase Reaction / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology; D002097:C-Reactive Protein / Q000032:analysis / Q000502:physiology*; D003167:Complement Activation / Q000502:physiology*; D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D001026:Coronary Artery Bypass; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011184:Postoperative Period; D011446:Prospective Studies; D012044:Regression Analysis; D013997:Time Factors
chemical_list: D003176:Complement C3; D003181:Complement C4; D002097:C-Reactive Protein