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J Thorac Cardiovasc Surg 2007;134:74-81
© 2007 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

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

Sara Arab, PhDc,*, Igor E. Konstantinov, MD, PhDa,*, Cathy Boscarino, MSca, Eva Cukerman, BScc, Alessandro Mori, BSca, Jia Li, MD, PhDb, Peter P. Liu, MDc, Andrew N. Redington, MDb, John G. Coles, MDa,*,*

a Division of Cardiovascular Surgery, Toronto General Hospital, University of Toronto, Toronto, Canada
b Division of Cardiology, Toronto General Hospital, University of Toronto, Toronto, Canada
c Hospital for Sick Children, Richard Lewar Centre of Excellence, Toronto General Hospital, University of Toronto, Toronto, Canada.

Received for publication June 13, 2006; revisions received January 2, 2007; accepted for publication January 8, 2007.

* Address for reprints: Dr John G. Coles, Division of Cardiovascular Surgery, Hospital for Sick Children, 555 University Avenue, Toronto, M5G 1X8, Canada. (Email: john.coles{at}sickkids.ca).

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.

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






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