Early gene expression profiles during intraoperative myocardial ischemia-reperfusion in cardiac surgery

Objective

The effects of cold cardioplegic arrest and reperfusion on human ventricular gene expression are unknown. We tested the hypothesis that intraoperative ischemia-reperfusion under conditions of blood cardioplegic arrest would induce a unique myocardial genomic profile indicative of a cardioprotective response.

Methods

Right ventricular samples were serially acquired during surgical repair of ventricular septal defect.

Results

Expression profiling revealed 3 patterns of gene expression: (1) increased expression above control levels within 1 hour of cardioplegic arrest, with further amplification during early reperfusion; (2) increased expression limited to the reperfusion phase; and (3) reduced expression during reperfusion. Functional annotation and network mapping of differentially expressed genes indicated activation of multiple signaling pathways regulated by phosphatidylinositide 3′-OH kinase convergent on cellular growth and reparative programs. Also observed was increased expression of genes regulating hemoglobin synthesis, suggesting a novel cardioprotective pathway evoked during ischemia-reperfusion.

Conclusion

Reversible myocardial ischemia-reperfusion during cardiac surgery is associated with an immediate genomic response that predicts a net cardioprotective phenotype.

CTSNet classification: 20, 29, 31

Abbreviations and Acronyms: ANOVA, analysis of variance, BSA, body surface area, GAPDH, glyceraldehyde-3-phosphate dehydrogenase, I/R, ischemia and reperfusion, IGF, insulin-like growth factor, IPC, ischemic preconditioning, MIAME, Minimum Information About a Microarray Experiment, qPCR, quantitative polymerase chain reaction, RVOT, resection of the right ventricular outflow, TRNA, total RNA, VEGF, vascular endothelial growth factor, VSD, ventricular septal defect