Complement activation after uncomplicated coronary artery bypass grafting: role of strict glucose control

Introduction

The complement system is a key component in the SIRS response after cardiac surgery. The aim of this study was to investigate whether strict glucose control modifies complement activation in this setting and to analyze the route of complement activation.

Methods

We performed a randomized trial in 20 adult patients after coronary artery bypass grafting (CABG). Patients were assigned to receive intensive or conventional insulin treatment immediately after admission to the ICU. Components of the complement system were determined by ELISA. Changes in complement levels over time were analyzed with one-way ANOVA repeated measures.

Results

Blood glucose levels were significantly lower in the intensive treatment group (P < 0.003). Serum concentrations of terminal complement complex were increased on admission to the ICU in both groups (2.80 ± 1.45 AU/ml vs 3.21 ± 2.17 AU/ml, P = 0.817) and declined significantly thereafter. All complement activation pathways converge at the point of C3 activation. The C3bc concentration was strongly increased on admission in both groups (78.9 ± 36.7 AU/ml vs 103.4 ± 68.0 AU/ml, P = 0.355) and declined in the following hours with a second peak at 8 hours after admission (P = 0.005). C3bBbP (alternative pathway activation) was increased on admission in both groups (106.44 ± 42.72 AU/ml vs 144.44 ± 73.51 AU/ml respectively, P = 0.199), followed by a significant decline in the following hours (P < 0.001). C1rs–C1inh complexes (classical pathway) were increased on admission in both groups (38.00 ± 12.27 AU/ml vs 40.78 ± 16.41 AU/ml, P = 0.690), followed in time by a gradual decrease and later by an increase (P < 0.001). No differences in C4bc (combined classical and lectin pathway) concentrations were measured between the treatment groups, and the concentrations remained constant during ICU stay. MBL (lectin pathway) concentrations were comparable in both treatment groups and did not change significantly during the 24-hour follow-up.

Conclusion

Strict glucose regulation does not alter the concentration of complement components or route of activation. Complement activation after CABG shows a biphasic pattern. Initially complement is activated trough the classical/lectin pathway and augmented by the alternative pathway. In a second phase, complement is activated by the classical/lectin pathway to the point of C3b formation without production of terminal complement complexes, indicating inhibition beyond C3b.