Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Ann Thorac Surg. 2018 Nov;106(5):1379-1387. doi: 10.1016/j.athoracsur.2018.06.016. Epub 2018 Jul 17.
During cardiac surgery with cardiopulmonary bypass, delivery of cardioplegia solution to achieve electromechanical cardiac quiescence is obligatory. The addition of lidocaine to cardioplegia has advantages, although its consequences at a molecular level remain unclear. We performed whole-genome RNA sequencing of the human left ventricular (LV) myocardium to elucidate the differences between whole-blood (WB) cardioplegia with and without addition of lidocaine (LC) on gene expression.
We prospectively enrolled 130 patients undergoing aortic valve replacement surgery. Patients received high-potassium blood cardioplegia either with (n = 37) or without (n = 93) lidocaine. The LV apex was biopsied at baseline, and after an average of 74 minutes of cold cardioplegic arrest. We performed differential gene expression analysis for 18,258 genes between these 2 groups. Clinical and demographic variables were adjusted in the model. Gene ontology (GO) and network enrichment analysis of the retained genes were performed using g:Profiler and Cytoscape.
A total of 1,298 genes were differentially expressed between cardioplegic treatments. Compared with the WB group, genes upregulated in the LC group were identified by network enrichment to play a protective role in ischemic injury by inhibiting apoptosis, increasing transferrin endocytosis, and increasing cell viability. Downregulated genes in the LC group were identified to play a role in inflammatory diseases, oxygen transport, and neutrophil aggregation.
The addition of lidocaine to cardioplegia had pronounced effects on a molecular level with genes responsible for decreased inflammation, reduced intracellular calcium binding, enhanced antiapoptotic protection, augmented oxygen accessibility through transferrins, and increased cell viability showing measurable differences.
在体外循环心脏手术中，必须输送心脏停搏液以实现机电心脏静止。虽然利多卡因加入心脏停搏液有其优势，但在分子水平上的后果仍不清楚。我们对人的左心室（LV）心肌进行了全基因组 RNA 测序，以阐明全血（WB）心脏停搏液中加入和不加入利多卡因（LC）对基因表达的差异。
我们前瞻性地招募了 130 名接受主动脉瓣置换手术的患者。患者接受高钾血心脏停搏液，其中 37 例（n=37）或不加入利多卡因（n=93）。在冷心脏停搏平均 74 分钟后，从 LV 心尖部取活检。我们对这两组之间的 18258 个基因进行了差异基因表达分析。在模型中调整了临床和人口统计学变量。使用 g:Profiler 和 Cytoscape 对保留基因进行了基因本体论（GO）和网络富集分析。
在心脏停搏治疗之间，共鉴定出 1298 个差异表达基因。与 WB 组相比，LC 组上调的基因通过网络富集被鉴定为通过抑制细胞凋亡、增加转铁蛋白内吞作用和增加细胞活力在缺血性损伤中发挥保护作用。LC 组下调的基因被鉴定为在炎症性疾病、氧运输和中性粒细胞聚集中发挥作用。
在分子水平上，利多卡因加入心脏停搏液有显著影响，与炎症减少、细胞内钙结合减少、抗凋亡保护增强、通过转铁蛋白增加氧气可及性以及细胞活力增加相关的基因显示出可测量的差异。
