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Heparin-coated cardiopulmonary bypass equipment. II. Mechanisms for reduced complement activation in vivo
V Videm1, T E Mollnes, K Bergh
1Department of Surgery A, Institute for Surgical Research, Department of Anaesthesiology, and Department of Clinical Chemistry, The National Hospital, Oslo University, Oslo, Norway.
Insights
Heparin-coated cardiopulmonary bypass equipment reduced complement activation, specifically C3bc and terminal complement complex formation, during heart surgery. This suggests heparin coating is beneficial for mitigating complement-mediated inflammatory responses.
Area of Science:
- Cardiovascular Surgery
- Immunology
- Biomaterials Science
Background:
- Complement activation during cardiopulmonary bypass (CPB) can lead to inflammatory responses.
- Heparin coating of CPB equipment is utilized to mitigate these effects.
Purpose of the Study:
- To investigate the mechanisms by which heparin coating reduces complement activation during CPB.
- To compare complement activation markers in patients undergoing CPB with heparin-coated versus uncoated equipment.
Main Methods:
- Randomized trial comparing Duraflo II heparin-coated (n=15) versus uncoated (n=14) CPB sets in adult coronary artery bypass grafting patients.
- Analysis of blood samples for complement activation products (C1rs-C1 inhibitor, Bb, C4bc, C3bc, C5a-desArg, terminal complement complex) using enzyme immunoassays.
Main Results:
- Heparin coating increased C1 activation initially but significantly reduced C3bc and terminal complement complex formation (P=.03 and P<.01, respectively).
- Bb and C5a-desArg tended to increase less with heparin coating (P=.22 and P=.13).
- Terminal complement complex concentrations correlated with alternative pathway activation (Bb, C3bc).
Conclusions:
- Heparin coating of CPB equipment effectively inhibits C3bc and terminal complement complex formation, despite initial C1 activation.
- Terminal complement complex formation appears linked to alternative pathway activation and may serve as a marker for CPB circuitry differences.
- The observed reduction in complement activation suggests a benefit of heparin-coated CPB equipment in clinical heart surgery.
Objective:
Our objective was to study mechanisms for reduced complement activation by heparin coating of cardiopulmonary bypass equipment in clinical heart surgery.
Methods:
Adults undergoing elective coronary artery bypass grafting were randomized to cardiopulmonary bypass with Duraflo II heparin-coated (n = 15) or uncoated (n = 14) sets (Duraflo coating surface; Baxter International, Inc, Deerfield, Ill). Blood samples were analyzed with the use of enzyme immunoassays for C1rs-C1 inhibitor complexes and the activation products Bb, C4bc, C3bc, C5a-desArg, and the terminal complement complex. Data were compared by repeated-measures analysis of variance.
Results:
C1 was activated during bypass, and increases in C1rs-C1 inhibitor complexes were larger with heparin coating (P =.03). C4bc increased after administration of protamine, without intergroup differences (P =.69). Bb (P =.22) and C5a-desArg (P =.13) tended to increase less with heparin coating. Formation of C3bc (P =.03) and the terminal complement complex (P <.01) was significantly reduced with heparin coating. C5a-desArg increased 2-fold during bypass, whereas the terminal complement complex increased 10- to 20-fold. Maximal terminal complement complex concentrations were significantly correlated to maximal Bb and C3bc (R = 0.6, P <.001), but not to C1rs-C1 inhibitor complexes or C4bc (R < 0.05, P >.8).
Conclusions:
C1 activation during bypass was increased by heparin coating, but further classical pathway activation was held in check until administration of protamine. Heparin coating significantly inhibited C3bc and terminal complement complex formation. Terminal complement complex concentrations were related to alternative pathway activation and may be useful for evaluation of differences in bypass circuitry. Increases and intergroup differences in terminal complement complex concentrations were much larger than those in C5a-desArg.