Activation of complement factor B contributes to postoperative myocardial necrosis after
cardiac surgery
Author(s): Nistal-Nuño, Beatriz, Zhang M., Haddadin A.S., Hines R., Mangi A.A., Hou Y.
Institute(s): Yale University School of Medicine, Dept of Anesthesiology, New Haven, United States.
Text: Objective: Cardiopulmonary bypass (CPB) and aortic cross clamping (AXCL) during cardiac surgery lead to global heart ischemia, contributing to postoperative myocardial necrosis. Basic science studies have shown that ischemia/reperfusion of heart tissue elicits an acute inflammatory response, involving several complement factors. Anticomplement
C5 has been tested in clinical trials with positive results. However, activation of earlier complement factors would be unaffected. Animal model studies suggested that complement factor B (fB), an initial factor in the alternative pathway, may be involved in postoperative myocardial necrosis. Whether fB plays a similar role in humans has not been determined. To investigate the role of fB in postoperative myocardial necrosis, we evaluated fB activation in cardiac surgery patients.
Methods: A total of 105 adult patients undergoing elective cardiac surgery with CPB were recruited after IRB approval. Blood was sampled from the coronary and peripheral circulations of cardiac patients at 7 defined perioperative periods identifying major stages in the surgery. fB activation was evaluated by ELISA assay and Western blotting, and was correlated with the myocardial necrosis marker, cardiac troponin I (cTnI). Statistically significant correlations between the levels of Bb, the active fragment of fB, and the levels of cTnI at designated time points were determined using Spearman´s correlation. Multivariate regression analysis was used to test whether perioperative Bb levels can independently predict postoperative cTnI increases. P< 0.05 was considered to be
statistically significant.
Results: Levels of Bb increased significantly in the coronary circulation following ischemia compared with prior to application of AXCL (before AXCL = 2.4 ± 2.0 μg/ml; after AXCL cessation = 4.4 ± 2.9 μg/ml, P < 0.01), and increased in peripheral blood at major steps in cardiac surgery (P< 0.05 at all time points). Univariate analysis showed that perioperative Bb levels in the coronary and peripheral circulations correlated significantly with the postoperative cTnI levels (P< 0.01 at all time points). Multivariate analysis revealed that these correlations were dependent on the time lengths of CPB and AXCL.
Conclusions: Our study is the first report to demonstrate that AXCL caused significant changes in Bb in the coronary and peripheral circulation. This study indicates that fB activation contributes directly to postoperative myocardial necrosis.

Activation of complement factor B contributes to postoperative myocardial necrosis after cardiac surgery