Arab Sara, Konstantinov Igor E, Boscarino Cathy, Cukerman Eva, Mori Alessandro, Li Jia, Liu Peter P, Redington Andrew N, Coles John G
Richard Lewar Centre of Excellence, Toronto General Hospital, University of Toronto, Toronto, Canada.
J Thorac Cardiovasc Surg. 2007 Jul;134(1):74-81, 81.e1-2. doi: 10.1016/j.jtcvs.2007.01.025.
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.
Right ventricular samples were serially acquired during surgical repair of ventricular septal defect.
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.
Reversible myocardial ischemia-reperfusion during cardiac surgery is associated with an immediate genomic response that predicts a net cardioprotective phenotype.
心脏冷停搏和再灌注对人类心室基因表达的影响尚不清楚。我们检验了这样一个假设，即在血液停搏条件下的术中缺血-再灌注会诱导出一种独特的心肌基因组图谱，表明存在心脏保护反应。
在室间隔缺损手术修复过程中连续获取右心室样本。
表达谱分析揭示了3种基因表达模式：（1）在心脏停搏1小时内表达高于对照水平，并在早期再灌注期间进一步增强；（2）表达增加仅限于再灌注阶段；（3）在再灌注期间表达降低。对差异表达基因的功能注释和网络映射表明，磷脂酰肌醇3'-OH激酶调节的多个信号通路被激活，这些通路汇聚于细胞生长和修复程序。还观察到调节血红蛋白合成的基因表达增加，提示在缺血-再灌注期间引发了一种新的心脏保护途径。
心脏手术期间可逆性心肌缺血-再灌注与一种即时的基因组反应相关，该反应预示着一种净心脏保护表型。
