Preoperative gene expression may be associated with neurocognitive decline after cardiopulmonary bypass

Objective Despite advances in surgical techniques, neurocognitive decline after cardiopulmonary bypass remains a common and serious complication. We have previously demonstrated that patients with neurocognitive decline have unique genetic responses 6 hours after cardiopulmonary bypass when compared with normal patients. We used genomic microarray to objectively investigate whether patients with neurocognitive decline had associated preoperative gene expression profiles and how these profiles changed up to 4 days after surgery. Methods Patients undergoing cardiac surgery underwent neurocognitive assessments preoperatively and 4 days after surgery. Skeletal muscle was collected intraoperatively. Whole blood collected before cardiopulmonary bypass, 6 hours after cardiopulmonary bypass, and on postoperative day 4 was hybridized to Affymetrix Gene Chip U133 Plus 2.0 microarrays (Affymetrix Inc, Santa Clara, Calif). Gene expression in patients with neurocognitive decline was compared with gene expression in the normal group using JMP Genomics (SAS Institute Inc, Cary, NC). Only genes that were commonly expressed in the 2 groups with a false discovery rate of 0.05 and a fold change greater than 1.5 were carried forward to pathway analysis using Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, Calif). Microarray gene expression was validated by Green real-time polymerase chain reaction and Western blotting. Results Neurocognitive decline developed in 17 of 42 patients. A total of 54,675 common transcripts were identified on microarray in each group across all time points. Preoperatively, there were 140 genes that were significantly altered between the normal and neurocognitive decline groups ( P Conclusions Patients in whom neurocognitive decline developed after cardiopulmonary bypass had increased differential gene expression before surgery versus patients in whom neurocognitive decline did not develop. Although significant differences in gene expression also existed postoperatively, these differences gradually decreased over time. Preoperative gene expression may be associated with neurologic injury after cardiopulmonary bypass. Further investigation into these genetic pathways may help predict patient outcome and guide patient selection.