title: No prominent role for terminal complement activation in the early myocardial reperfusion phase following cardiac surgery.
abstract: OBJECTIVE
  Complement activation is considered an important mediator of myocardial ischaemia/reperfusion (I/R) injury. Although complement inhibitors are highly effective in animals, clinical trials fail to show a substantial benefit in humans. This raises questions on the role of complement activation in human myocardial I/R injury.
  
  
  METHODS
  Soluble C5b-9, i.e. terminal complement complex, and C5a were assessed in patients with non-ischaemic (n = 10) and ischaemic heart failure (n = 10), and patients without heart failure (n = 10) undergoing cardiac surgery. To study the pathophysiology of human I/R injury, a model of arteriovenous measurements over the reperfused heart was applied at consecutive time points during the early reperfusion phase. Furthermore, C3d and C5b-9 depositions in pre-reperfusion myocardial and endomyocardial tissue were evaluated and compared to pre-transplantation tissue from myocardial allografts.
  
  
  RESULTS
  Simultaneous assessment of soluble C5b-9 and C5a in systemical and myocardial venous blood samples revealed the absence of net release from the reperfused heart in all three patient groups. Biopsies of patients with non-ischaemic heart failure showed the most abundant myocardial depositions of C3d and C5b-9: 4.8 times more C3d (P = 0.008) and 4.7 times more C5b-9 (P = 0.004) than donor tissue. Also C3d was abundantly present in endomyocardial tissue of both heart failure groups compared to donors (both P = 0.02).
  
  
  CONCLUSIONS
  No evidence was obtained that terminal complement activation is involved in the acute phase following myocardial reperfusion. Since complement deposition was already present before reperfusion, human complement inhibition might be more beneficial in the preoperative phase than during reperfusion.
authors.affiliation: Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands. k.a.kortekaas@lumc.nl
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Kortekaas
authors.forename: Pieter
authors.initials: P
authors.lastname: van der Pol
authors.forename: Jan H N
authors.initials: JH
authors.lastname: Lindeman
authors.forename: Carla C
authors.initials: CC
authors.lastname: Baan
authors.forename: Cees
authors.initials: C
authors.lastname: van Kooten
authors.forename: Robert J M
authors.initials: RJ
authors.lastname: Klautz
mesh_terms: D000368:Aged; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D003167:Complement Activation / Q000502:physiology*; D015933:Complement C3d / Q000378:metabolism; D003182:Complement C5 / Q000378:metabolism; D006333:Heart Failure / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000276:immunology*; D009206:Myocardium / Q000276:immunology
chemical_list: D003182:Complement C5; D015933:Complement C3d; C037453:complement C5b-7 complex