Dalal Rahul S, Sabe Ashraf A, Elmadhun Nassrene Y, Ramlawi Basel, Sellke Frank W
Cardiovascular Research Center, Warren Alpert Medical School, Brown University, Providence, RI, USA.
Methodist DeBakey Heart & Vascular Center, Methodist Hospital, Houston, Texas, USA.
Braz J Cardiovasc Surg. 2015 Sep-Oct;30(5):520-32. doi: 10.5935/1678-9741.20150070.
Atrial fibrillation and neurocognitive decline are common complications after cardiopulmonary bypass. By utilizing genomic microarrays we investigate whether gene expression is associated with postoperative atrial fibrillation and neurocognitive decline.
Twenty one cardiac surgery patients were prospectively matched and underwent neurocognitive assessments pre-operatively and four days postoperatively. The whole blood collected in the pre-cardiopulmonary bypass, 6 hours after-cardiopulmonary bypass, and on the 4th postoperative day was hybridized to Affymetrix Gene Chip U133 Plus 2.0 Microarrays. Gene expression in patients who developed postoperative atrial fibrillation and neurocognitive decline (n=6; POAF+NCD) was compared with gene expression in patients with postoperative atrial fibrillation and normal cognitive function (n=5; POAF+NORM) and patients with sinus rhythm and normal cognitive function (n=10; SR+NORM). Regulated genes were identified using JMP Genomics 4.0 with a false discovery rate of 0.05 and fold change of >1.5 or <-1.5.
Eleven patients developed postoperative atrial fibrillation. Six of these also developed neurocognitive decline. Of the 12 patients with sinus rhythm, only 2 developed neurocognitive decline. POAF+NCD patients had unique regulation of 17 named genes preoperatively, 60 named genes six hours after cardiopulmonary bypass, and 34 named genes four days postoperatively (P<0.05) compared with normal patients. Pathway analysis demonstrated that these genes are involved in cell death, inflammation, cardiac remodeling and nervous system function.
Patients who developed postoperative atrial fibrillation and neurocognitive decline after cardiopulmonary bypass may have differential genomic responses compared to normal patients and patients with only postoperative atrial fibrillation, suggesting common pathophysiology for these conditions. Further exploration of these genes may provide insight into the etiology and improvements of these morbid outcomes.
心房颤动和神经认知功能减退是体外循环后的常见并发症。通过使用基因组微阵列，我们研究基因表达是否与术后心房颤动和神经认知功能减退相关。
前瞻性地匹配了21例心脏手术患者，并在术前和术后4天进行了神经认知评估。在体外循环前、体外循环后6小时和术后第4天采集的全血与Affymetrix Gene Chip U133 Plus 2.0微阵列进行杂交。将发生术后心房颤动和神经认知功能减退的患者（n = 6；POAF+NCD）的基因表达与术后心房颤动且认知功能正常的患者（n = 5；POAF+NORM）以及窦性心律且认知功能正常的患者（n = 10；SR+NORM）的基因表达进行比较。使用JMP Genomics 4.0识别调控基因，错误发现率为0.05，倍数变化>1.5或<-1.5。
11例患者发生了术后心房颤动。其中6例还出现了神经认知功能减退。在12例窦性心律的患者中，只有2例出现了神经认知功能减退。与正常患者相比，POAF+NCD患者术前有17个命名基因、体外循环后6小时有60个命名基因、术后4天有34个命名基因受到独特调控（P<0.05）。通路分析表明，这些基因参与细胞死亡、炎症、心脏重塑和神经系统功能。
与正常患者和仅发生术后心房颤动的患者相比，体外循环后发生术后心房颤动和神经认知功能减退的患者可能具有不同的基因组反应，提示这些情况存在共同的病理生理学机制。对这些基因的进一步探索可能有助于深入了解这些疾病的病因并改善这些不良结局。
