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[Effect of complement 4 genetic polymorphism on complement activation during cardiopulmonary bypass in open heart
1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Insights
Complement 4 (C4) genetic polymorphism influences complement activation during pediatric open-heart surgery. The OOBB C4 phenotype is linked to the most severe complement activation and lung damage during cardiopulmonary bypass (CPB).
Area of Science:
- Immunogenetics
- Cardiovascular Surgery
- Pediatric Critical Care
Context:
- Extracorporeal circulation during open-heart surgery activates the complement system.
- Genetic variations, such as complement 4 (C4) polymorphism, may influence this activation.
- Understanding these interactions is crucial for managing perioperative complications in children.
Purpose:
- To investigate the relationship between C4 genetic polymorphism and complement activation markers (C4a, C3a) during pediatric cardiopulmonary bypass (CPB).
- To assess the impact of C4 phenotypes on lung function (lung compliance) during and after CPB.
- To correlate specific C4 phenotypes with the severity of complement activation and lung injury.
Summary:
- One hundred fifty-six children undergoing open-heart surgery were analyzed for C4 phenotypes.
- Complement activation (increased C4a and C3a) and decreased lung compliance were observed during CPB and after protamine infusion.
- The OOBB C4 phenotype exhibited the most significant complement activation and lung dysfunction, particularly after protamine administration.
Impact:
- The study reveals that the complement system is activated via both alternative (CPB) and classic (protamine-heparin) pathways.
- Individuals with the OOBB C4 phenotype experience the most pronounced complement activation and lung damage during CPB.
- The OOBB phenotype is more prevalent in Chinese populations, suggesting potential ethnic-specific risks in pediatric cardiac surgery.
Objective:
To evaluate the relation between complement 4 genetic polymorphism and complement activation during extracorporeal circulation in open heart surgery among children.
Methods:
One hundred and fifty-six children to undergo open heart surgery with cardiopulmonary bypass in Wuhan and surrounding areas were investigated. Blood samples were obtained before the operation to analyze the C4 phenotypes by crossed immunoelectrophoresis. Before the initiation of CPB, at the end of CPB, and 10 minutes after protamine infusion, arterial blood samples were drawn to test the C4a and C3a with radioimmunoassay and lung compliance was recorded.
Results:
The frequencies of C4 genetic phenotypes AABB, AOBB, OOBB, AABO, and AAOO were 51.28%, 17.95%, 4.49%, and 19.80% respectively among the investigated children. At the end of CPB, The C4a levels remained almost the same, and C3a levels increased significantly. Ten minutes after the protamine infusion, significant increase was seen in the levels of both C4a and C3a, especially in the OOBB phenotype group followed by AOBB phenotype group. The lung compliance began to decrease by the end of CPB, most significantly in the OOBB phenotype group, followed by the AOBB group, along with the increase of C4a level.
Conclusion:
The complement system is activated by the alternative pathway during CPB and by the classic way during the formation of protamine-heparin complexes. The complement system is activated and the lung function is damaged the most seriously during CPB among the persons with OOBB phenotype. The frequency of OOBB phenotype is higher among Chinese than among Caucasians.