循环性死亡(DCD)后的心脏捐赠主要通过常温血液灌注(NBP)维持。然而,研究表明,低温晶体灌注(HCP)优于血液灌注,以恢复左心室(LV)的收缩力。然而,尚未研究HCP和NBP后DCD心脏中心肌和冠状动脉的转录组变化。在猪模型中,收集DCD心脏并通过NBP维持4小时(DCD-BP组,N=8)或HCP与含氧组氨酸-色氨酸-酮戊二酸(HTK)溶液(DCD-HTK,N=8),然后用新鲜血液再灌注2h。在DCD组(N=8)中,心脏在采购后立即进行再灌注。在对照组(N=7)中,没有引起循环性死亡。我们使用微阵列(25,470个基因)对LV心肌和左前降支(LAD)样品进行了转录组学。我们应用Boruta算法进行变量选择以识别相关基因。在DCD-BP组中,与DCD相比,6个基因在心肌中被调节,1915个基因在LAD中被调节。在DCD-HTK组中,259个基因在心肌中下调,27个基因在LAD中下调;52个基因在心肌中上调,765个基因在LAD中上调,与DCD组相比。我们确定了七个与群体识别相关的基因:ITPRIP,G3BP1,ARRDC3,XPO6,NOP2,SPTSSA,IL-6NBP导致参与线粒体钙积累和ROS产生的基因上调,微血管内皮发芽的减少,和炎症。HCP导致NF-κB-相关基因的下调,STAT3-,和SASP激活和炎症。
Donation after circulatory death (DCD) hearts are predominantly maintained by normothermic blood perfusion (NBP). Nevertheless, it was shown that hypothermic crystalloid perfusion (HCP) is superior to blood perfusion to recondition left ventricular (LV) contractility. However, transcriptomic changes in the myocardium and coronary artery in DCD hearts after HCP and NBP have not been investigated yet. In a pig model, DCD hearts were harvested and maintained for 4 h by NBP (DCD-BP group, N = 8) or HCP with oxygenated histidine-tryptophane-ketoglutarate (HTK) solution (DCD-HTK, N = 8) followed by reperfusion with fresh blood for 2 h. In the DCD group (N = 8), hearts underwent reperfusion immediately after procurement. In the control group (N = 7), no circulatory death was induced. We performed transcriptomics from LV myocardial and left anterior descending (LAD) samples using
microarrays (25,470 genes). We applied the Boruta algorithm for variable selection to identify relevant genes. In the DCD-BP group, compared to DCD, six genes were regulated in the myocardium and 1915 genes were regulated in the LAD. In the DCD-HTK group, 259 genes were downregulated in the myocardium and 27 in the LAD; and 52 genes were upregulated in the myocardium and 765 in the LAD, compared to the DCD group. We identified seven genes of relevance for group identification: ITPRIP, G3BP1, ARRDC3, XPO6, NOP2, SPTSSA, and IL-6. NBP resulted in the upregulation of genes involved in mitochondrial calcium accumulation and ROS production, the reduction in microvascular endothelial sprouting, and inflammation. HCP resulted in the downregulation of genes involved in NF-κB-, STAT3-, and SASP-activation and inflammation.