Abstract 2276: Differential complement activation following on- and off-pump Coronary artery Bypass Surgery explained by alternative pathway activation
Introduction. Coronary Artery Bypass Surgery (CABG) with the off pump (OFFCAB) technique may cause less inflammatory activation than using cardiopulmonary bypass (ONCAB). ONCAB procedures activate complement more but the relative contribution of classical and alternative pathways is unknown. We hypothesised OFFCAB procedures would produce less alternative pathway activation and performed a prospective, observational study to examine classical, alternative and final pathway activation in OFFCAB and ONCAB patients.
Methods. Forty-two consecutive CABG patients were recruited over an 8 month period. At the discretion of the surgeon and patient, 26 underwent ONCAB and 16 OFFCAB procedures. Blood was taken pre, intra and post operatively for 24 hrs for assessment of inflammatory and ischaemic serum markers. Complement components Bb, C4d, iC3b and sC5b-9 (i.e. the terminal complement complex or TCC) were assayed as markers of complement activation.
Results. Most striking was a greater activation of the alternative pathway in the ONCAB group. Bb levels rose significantly (between pre- and 8hr post-operative time-points) following ONCAB based surgery (2.6 Vs 5.6 μg/ml respectively). OFFCAB surgery produced no significant alternative pathway activation. At peak alternative pathway activation (8hr post surgery), serum Bb levels were 1.7 fold higher in ONCAB vs OFFCAB patients (5.6 Vs 3.9 μg/ml respectively). These novel data reveal marked alternative pathway activation associated with ONCAB. Serum C4d analysis revealed that both procedures were both associated with a similar degree of classical pathway activation. In keeping with previous data, the TCC assay indicated significantly greater global complement activation by ONCAB than OFFCAB. Other inflammatory and ischaemic serum markers rose significantly and similarly in both groups.
Conclusion. We provide the first analysis of on- and off-pump CABG in the activation of the classical, alternative and final complement pathways. ONCAB causes greater global complement activation. We conclude this may be largely due to activation of the alternative pathway by ONCAB, since OFFCAB did not significantly activate this pathway. Classical pathway activation was similar in both groups.