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.


CONCLUSIONS
Reversible myocardial ischemia-reperfusion during cardiac surgery is associated with an immediate genomic response that predicts a net cardioprotective phenotype.
Arab
Sara
S
Richard Lewar Centre of Excellence, Toronto General Hospital, University of Toronto, Toronto, Canada.
Konstantinov
Igor E
IE
Boscarino
Cathy
C
Cukerman
Eva
E
Mori
Alessandro
A
Li
Jia
J
Liu
Peter P
PP
Redington
Andrew N
AN
Coles
John G
JG
D000222:Adaptation, Physiological / Q000235:genetics; D000704:Analysis of Variance; D001706:Biopsy; D002315:Cardiopulmonary Bypass; D002675:Child, Preschool; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D005914:Globins / Q000235:genetics; D006345:Heart Septal Defects, Ventricular / Q000150:complications / Q000473:pathology / Q000601:surgery*; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D007223:Infant; D007432:Intraoperative Period; D019194:Ischemic Preconditioning; D046228:Microarray Analysis / Q000592:standards; D017202:Myocardial Ischemia / Q000209:etiology / Q000235:genetics* / Q000601:surgery*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D012343:RNA, Transfer / Q000302:isolation & purification; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D042461:Vascular Endothelial Growth Factor A; D005914:Globins; D012343:RNA, Transfer