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  • Title: Extracorporeal Membrane Oxygenation Improving Survival and Alleviating Kidney Injury in a Swine Model of Cardiac Arrest Compared to Conventional Cardiopulmonary Resuscitation.
    Author: Yuan XL, Li CS, Zhang Y, Ling JY, Zhang Q, Liang Y, Liu B, Zhao LX.
    Journal: Chin Med J (Engl); 2018 Aug 05; 131(15):1840-1848. PubMed ID: 30058582.
    Abstract:
    BACKGROUND: Acute kidney injury (AKI) frequently occurs in cardiopulmonary resuscitation patients. Studies comparing the effects of extracorporeal membrane oxygenation (ECMO) with conventional cardiopulmonary resuscitation (CCPR) on AKI were rare. This study aimed to compare the effects of ECMO with those of CCPR on survival rate and AKI and explore the underlying mechanisms in a swine model of cardiac arrest (CA). METHODS: Sixteen male pigs were treated with ventricular fibrillation to establish CA model and then underwent CCPR (CCPR group, n = 8) or ECMO during cardiopulmonary resuscitation (ECPR group, n = 8). The study endpoints were 6 h after return of spontaneous circulation (ROSC) or death. Serum and urine samples were collected at baseline and during the 6 h after ROSC. The biomarkers of AKI were detected by enzyme-linked immunosorbent assay. The apoptosis of renal tubular epithelial cells was discovered by transmission electron microscope (TEM) and terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Apoptosis-related genes were detected by immune-staining and Western blotting. Data were compared by Student's t-test. RESULTS: All pigs in ECPR group were successfully resuscitated with a higher 6-h survival rate (8/8) compared to CCPR group (6/8). The expressions of AKI biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinase2 (TIMP2), insulin-like growth factor-binding protein 7 (IGFBP7), liver fatty acid-binding protein (LFABP), and kidney injury molecule1 (Kim-1) were all increased along with the time after ROSC in both groups and lower in ECPR group compared with CCPR group. Especially, products of urinary TIMP and IGFBP levels (TIMP*IGFBP) were significantly lower at ROSC4 (0.58 ± 0.10 ng2/ml2 vs. 1.18 ± 0.38 ng2/ml2, t = 4.33, P = 0.003) and ROSC6 (1.79 ± 0.45 ng2/ml2 vs. 3.00 ± 0.44 ng2/ml2, t = 5.49, P < 0.001); urinary LFABP was significantly lower at ROSC6 (0.74 ± 0.06 pg/ml vs. 0.85 ± 0.11 pg/ml, t = 2.41, P = 0.033); and urinary Kim-1 was significantly lower at ROSC4 (0.66 ± 0.09 pg/ml vs. 0.83 ± 0.06 pg/ml, t = 3.99, P = 0.002) and ROSC6 (0.73 ± 0.12 pg/ml vs. 0.89 ± 0.08 pg/ml, t = 2.82, P = 0.016). Under light microscope and TEM, the morphological injures in renal tissues were found to be improved in ECPR group. Moreover, apoptosis was also alleviated in ECPR group. CONCLUSIONS: Compared with CCPR, ECMO improves survival rate and alleviates AKI in a swine model of CA. The mechanism of which might be via downregulating AKI biomarkers and apoptosis in kidney. 体外膜肺氧合较心肺复苏可以提高猪心脏骤停模型生存率并减轻肾损伤摘要背景:急性肾损伤常见于心肺复苏病人,目前比较体外膜肺氧合(ECMO)和常规心肺复苏(CCPR)对急性肾损伤影响的研究极少,同时其潜在分子机制也少有研究。本研究旨在利用心脏骤停猪模型比较ECMO和CCPR对其生存率和急性肾损伤的影响同时探究相关机制。 方法:16只猪经室颤建立心脏骤停模型,同时分成两组,ECPR组接受CCPR和ECMO治疗(n=8);CCPR组只接受CCPR治疗(n=8)。研究终点为自主循环恢复(ROSC)6小时或死亡。收集基线及ROSC各时间点血清和尿液样本。急性肾损伤相关标志物经酶联免疫法检测。利用透射电镜和TUNEL方法观察肾小管上皮细胞凋亡水平。同时利用免疫染色和免疫印记检测凋亡相关基因。实验数据以平均值 ± 标准差比较并用Student's t-检验进行比较。 结果:ECPR组均成功复苏,其6小时生存率(8/8;100%)高于CCPR组(6/8;75%)。包括TIMP、IGFBP、LFABP、KIM-1在内的急性肾损伤标志物在ECPR和CCPR组均随观察时间而增加。同时发现ECPR组各标志物水平均显著低于CCPR组。特别是 ROSC4(0.58 ± 0.10 ng2/ml2 vs. 1.18 ± 0.38 ng2/ml2t=4.33,P=0.003)和ROSC6(1.79 ± 0.45 ng2/ml2 vs. 3.00 ± 0.44 ng2/ml2t=5.49,P<0.001)时间点的尿液TIMP与IGFBP水平之积;ROSC6时间点的尿液LFABP水平(0.74 ± 0.06 pg/ml vs. 0.85 ± 0.11 pg/ml,t=2.41,P=0.033);以及ROSC4(0.66 ± 0.09 pg/ml vs. 0.83 ± 0.06 pg/ml,t = 3.99,P = 0.002)和ROSC6(0.73 ± 0.12 pg/ml vs. 0.89 ± 0.08 pg/ml,t = 2.82, P = 0.016)时间点的尿液Kim-1水平。在光学显微镜和透射电镜下,均可观察到ECPR组肾组织形态损伤水平要低于CCPR组。ECPR组肾组织凋亡水平也得到了缓解。 结论:与常规心肺复苏相比,体外膜肺氧合可以提高心脏骤停生存率并缓解急性肾损伤。其分子机制可能是,体外膜肺氧合较常规心肺复苏降低了急性肾损伤标志物水平以及肾组织中的凋亡水平。.
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