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Published on: March 23, 2018
Complement activation during cardiopulmonary bypass and association with clinical outcomes
Rengina Kefalogianni1, Farah Kamani2, Mihaela Gaspar2
1Department of Immunology and Inflammation Imperial College London London UK.
Insights
Cardiopulmonary bypass (CPB) activates the complement system, increasing post-operative blood loss. Inhibiting complement activation may reduce bleeding in patients undergoing CPB surgery.
Area of Science:
- Immunology
- Cardiovascular Surgery
- Complement System Biology
Background:
- The complement system plays a crucial role in innate immunity.
- Activation of the complement cascade can lead to inflammatory responses and tissue damage.
- Understanding complement's role during cardiopulmonary bypass (CPB) is essential for mitigating surgical complications.
Purpose of the Study:
- To investigate the impact of unfractionated heparin (UFH), CPB, and protamine sulfate on complement activation.
- To assess the relationship between complement activation markers and post-operative blood loss in CPB patients.
Main Methods:
- Prospective, single-centre observational study involving 30 patients undergoing CPB.
- Measurement of complement components (C3, C4) and activation markers (C3a, C5a, Bb, SC5b-9) at different stages: pre-UFH, post-UFH, during CPB, post-protamine, and 12-24 hours post-surgery.
- Correlation analysis between complement levels and 24-hour post-operative drain volume.
Main Results:
- Unfractionated heparin (UFH) transiently decreased C3 and C4 levels, with no immediate effect on activation markers.
- Cardiopulmonary bypass (CPB) significantly increased complement activation markers (Bb, C3a, C5a, SC5b-9) while decreasing C3 and C4.
- Protamine sulfate reduced the alternative pathway activation marker Bb but did not affect classical pathway components.
- Post-operative blood loss correlated inversely with C3/C4 levels and positively with C3a, C5a, and SC5b-9 levels.
Conclusions:
- Complement system activation during CPB is linked to increased post-operative blood loss.
- Targeting complement activation pathways presents a potential therapeutic strategy for reducing bleeding complications in CPB patients.
Abstract:
In this prospective, single-centre observational study of 30 patients undergoing cardiopulmonary bypass (CPB), the effect of unfractionated heparin (UFH), CPB surgery and protamine sulphate on complement and on post-operative blood loss were assessed. Although C3 and C4 levels decreased significantly immediately following the administration of UFH, C3a, C5a, Bb fragment and SC5b-9 remained unchanged. During CPB, C3 and C4 continued to fall whilst both alternative and classical pathways activation markers, Bb, C3a, C5a and SC5b-9 increased significantly. Protamine sulphate had no effect on classical pathway components or activation markers but decreased alternative pathway activation marker Bb. Over the 12-24 h post-surgery, both classical and alternative pathway activation markers returned to baseline, whilst C3 and C4 levels increased significantly but not to baseline values. Total drain volume 24 h after the surgery showed a moderate inverse correlation with post-protamine C3 (r = -0.46, p = 0.01) and C4 (r = -0.57, p = 0.0009) levels, whilst a moderate positive correlation was observed with post-protamine C3a (r = 0.46, p = 0.009), C5a (r = 0.37, p = 0.04) and SC5b-9 (r = 0.56, p = 0.001) levels but not with Bb fragment (r = 0.25, p = 0.17). Thus, inhibition of complement activation may be a therapeutic intervention to reduce post-operative blood in patients undergoing CPB.
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