Gene Expression Changes in Leukocytes During Cardiopulmonary Bypass Are Dependent on Circuit Coating

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Abstract
Background— Cardiopulmonary bypass (CPB) results in a systemic inflammatory response. Leukocytes play a crucial role in inflammatory reactions. Their gene expression profile in the context of CPB is unknown. Methods and Results— In a prospective, randomized, and double-blind clinical trial, 12 male patients underwent elective coronary artery bypass grafting with either heparin-coated (group H) or protein-coated (group P) CPB circuits. Oligonucleotide microarray analyses of 22 283 genes were performed on circulating leukocytes, collected immediately before surgery and 6 hours after CPB. Microarray results were validated with real-time polymerase chain reaction. All patients had uneventful surgery, and no significant differences between groups were observed during the clinical course. Multiple statistical analyses with different methods were performed. Compared with preoperative expression at a threshold value of P P 4-fold increase and 27 exhibited a >4-fold decrease in group H, whereas only 7 genes exhibited upregulation and 7 revealed downregulation in group P. Microarray-pathway-profile-finder analyses determined 1405 upregulated and 1454 downregulated pathways in group H compared with 552 upregulated and 818 downregulated pathways in group P ( P Conclusions— Heparin coating resulted in a more profound alteration in leukocyte gene expression when compared with protein coating. Microarray analyses present an innovative approach for the evaluation and understanding of inflammatory reactions associated with CPB.