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.
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.
Authors: Jochen D Muehlschlegel; Danos C Christodoulou; David McKean; Joshua Gorham; Erica Mazaika; Mahyar Heydarpour; Grace Lee; Steven R DePalma; Tjorvi E Perry; Amanda A Fox; Stanton K Shernan; Christine E Seidman; Sary F Aranki; Jon G Seidman; Simon C Body Journal: Anesthesiology Date: 2015-03 Impact factor: 7.892
Authors: Mahyar Heydarpour; Julius Ejiofor; Michael Gilfeather; Gregory Stone; Josh Gorham; Christine E Seidman; Jon G Seidman; Maroun Yammine; Simon C Body; Sary F Aranki; Jochen D Muehlschlegel Journal: Ann Thorac Surg Date: 2018-07-17 Impact factor: 4.330