Abstract 1988: Genomic Expression Pathways Associated to Brain Injury after Cardiopulmonary Bypass
Background: Neurologic injury after cardiac surgery, often manifested as neurocognitive decline (NCD), is a common postoperative complication. We studied acute variations in gene expression profiles of patients with neurocognitive decline (NCD) and those without NCD (NORM) following cardiopulmonary bypass (CPB).
Methods: Forty two patients undergoing CABG and/or valve procedures using CPB were administered a validated neurocognitive battery preoperatively (PRE) and postoperatively at day 4 (POD4). NCD was defined as one standard deviation from baseline on ≥ 25% of tasks. Gene expression was assessed with Affymetrix GeneChip U133 Plus 2.0 (> 40,000 genes) from whole blood mRNA samples collected preoperatively and 6 hours (6H) postoperatively for fold-change calculation. Differential expression, clustering, gene ontology and canonical pathway analysis was performed. Validation of gene expression was performed with SYBR Green real time PCR.
Results: NCD patients (17 of 42 patients, 40.5%) were associated with a significantly different gene expression response compared to NORM patients. Compared with PRE samples, 6H samples had 531 up-regulated and 670 down-regulated genes uniquely in the NCD group compared to 2214 up-regulated and 558 down-regulated genes uniquely in the NORM group (p < 0.001, Lower confidence bound ≥ 1.2). Compared to patients in the NORM group, NCD patients had significantly different gene expression pathways involving inflammation (including FAS, IL2RB, CD59), antigen presentation (including HLA-DQ1, TAP1, TAP2) and cellular adhesion (including ICAM2, ICAM3, CAD7) as in table⇓ below.
Conclusion: Patients who develop NCD have inherently different genetic responses to CPB compared to patients without NCD. Genetic variations in pathways involving inflammation, antigen presentation and cellular adhesion may be important contributors to the pathophysiology of neurologic injury after CPB, and could become a target for prevention.