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No prominent role for terminal complement activation in the early myocardial reperfusion phase following cardiac surgery.
MedLine Citation:
PMID:  22408044     Owner:  NLM     Status:  Publisher    
OBJECTIVES: 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.
Kirsten A Kortekaas; Pieter van der Pol; Jan H N Lindeman; Carla C Baan; Cees van Kooten; Robert J M Klautz
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-9
Journal Detail:
Title:  European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery     Volume:  -     ISSN:  1873-734X     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804069     Medline TA:  Eur J Cardiothorac Surg     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands.
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