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Activation of the complement system during and after cardiopulmonary bypass surgery: postsurgery activation involves
P Bruins1, H te Velthuis, A P Yazdanbakhsh
1Department of Anaesthesiology, Academic Medical Centre, Amsterdam, The Netherlands.
Insights
Cardiac surgery activates complement in two phases. The first occurs during cardiopulmonary bypass (CPB), while the second phase involves C-reactive protein (CRP) and is linked to arrhythmias post-surgery.
Area of Science:
- Immunology
- Cardiovascular Surgery
- Biochemistry
Background:
- Complement activation is a known complication of cardiopulmonary bypass (CPB).
- The extracorporeal circuit during CPB is thought to be the primary trigger.
- The role of acute-phase proteins like C-reactive protein (CRP) in this process requires further investigation.
Purpose of the Study:
- To investigate mechanisms of complement activation during and after CPB.
- To explore the specific role of C-reactive protein (CRP) in perioperative complement activation.
- To correlate complement activation and CRP levels with clinical outcomes like arrhythmia.
Main Methods:
- Measured perioperative and postoperative levels of complement activation products (C3b/c, C4b/c), IL-6, CRP, and complement-CRP complexes in 19 patients undergoing myocardial revascularization.
- Analyzed the relationship between these markers and clinical symptoms.
- Utilized multivariate analysis to identify factors influencing CRP and C4b/c levels.
Main Results:
- Observed a biphasic complement activation pattern.
- The second phase of complement activation, involving CRP, peaked 2-3 days post-surgery.
- Peak C4b/c levels correlated significantly with the occurrence of arrhythmia.
Conclusions:
- Cardiac surgery with CPB induces biphasic complement activation.
- The early phase is linked to the CPB circuit, while the later phase involves CRP and is associated with clinical events.
- Baseline CRP levels and complement activation post-CPB are linked to postoperative arrhythmia.
Background:
Complement activation during cardiopulmonary bypass (CPB) surgery is considered to result from interaction of blood with the extracorporeal circuit. We investigated whether additional mechanisms may contribute to complement activation during and after CPB and, in particular, focused on a possible role of the acute-phase protein C-reactive protein (CRP).
Methods And Results:
In 19 patients enrolled for myocardial revascularization, perioperative and postoperative levels of complement activation products, interleukin-6 (IL-6), CRP, and complement-CRP complexes, reflecting CRP-mediated complement activation in vivo, were measured and related to clinical symptoms. A biphasic activation of complement was observed. The ratio between the areas under the curve of perioperative and postoperative C3b/c and C4b/c were 3:2 and 1:46, respectively. IL-6 levels reached a maximum at 6 hours post-surgery. CRP levels peaked on the second postoperative day. Each complement-CRP complex had peak levels on the second or third postoperative day. By multivariate analysis, maximum levels of CRP on the second postoperative day were mainly explained by C4b/c levels after protamine administration, leukocyte count on the second postoperative day, and preoperative levels of CRP. Peak levels of C4b/c after protamine administration (P=.0073) and on the second postoperative day correlated with the occurrence of arrhythmia on the same day (P=.0065).
Conclusions:
Cardiac surgery with CPB causes a biphasic complement activation. The first phase occurs during CPB and results from the interaction of blood with the extracorporeal circuit. The second phase, which occurs during the first 5 days after surgery, involves CRP, is related to baseline CRP levels, and is associated with clinical symptoms such as arrhythmia.