Gene expression changes in leukocytes during cardiopulmonary bypass are dependent on circuit coating.
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.


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<0.01, postoperative expression revealed 814 upregulated and 1187 downregulated genes in group H compared with 99 upregulated and 231 downregulated in group P (P<0.001). Fifty genes exhibited a >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<0.01). Pathways related to inflammatory response exhibited highest z scores in group H, reflecting cellular inflammatory activation.


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.
Seeburger
Joerg
J
Department of Thoracic, Cardiac, and Vascular Surgery, Eberhard Karls University, Tuebingen, Germany.
Hoffmann
Jan
J
Wendel
Hans Peter
HP
Ziemer
Gerhard
G
Aebert
Hermann
H
D000368:Aged; D000418:Albumins / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D002315:Cardiopulmonary Bypass / Q000009:adverse effects / Q000295:instrumentation*; D002453:Cell Cycle / Q000235:genetics; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D017558:Elective Surgical Procedures; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011184:Postoperative Period; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000494:pharmacology; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000235:genetics
D000418:Albumins; D020099:Coated Materials, Biocompatible; D011994:Recombinant Proteins; D006493:Heparin