No prominent role for terminal complement activation in the early myocardial reperfusion phase following cardiac surgery

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.

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