University of Leicester, Clinical Sciences Wing, Glenfield General Hospital , Leicester , United Kingdom.
National Heart and Lung Institute, Hammersmith Hospital Campus, Imperial College London , London , United Kingdom.
Am J Physiol Renal Physiol. 2018 May 1;314(5):F726-F735. doi: 10.1152/ajprenal.00319.2017. Epub 2017 Dec 20.
Acute kidney injury (AKI) is common complication of cardiac surgery; however, the phenotype of this condition is poorly defined. The aim of this study was to characterize changes in endothelial structure and function that underlie postcardiopulmonary bypass (post-CPB) AKI. Adult pigs ( n = 16) were randomized to undergo the following procedures ( n = 8 per group): group 1: sham operation, neck dissection with 2.5 h of general anesthesia; and group 2: CPB, 2.5 h of cardiopulmonary bypass. CPB resulted in the depletion of specific epitopes of glycosaminoglycans side chains of the endothelial glycocalyx: Dolichos biflorus agglutinin: mean difference (MD) [95% confidence interval (CI)], P value: -0.26 (-0.42, -0.09), P = 0.0024, Triticum vulgaris (wheat germ) agglutinin: -0.83 (-1.2, -0.38), P = 0.0005, and Ulex europaeus agglutinin 1: -0.25 (-0.49, -0.009), P = 0.041; endothelial membrane protein: thrombomodulin: -3.13 (-5.6, -0.65), P = 0.02; and adherens junction: VE-cadherin: -1.06 (-1.98, -0.145), P = 0.02. CPB also resulted in reductions in microvascular cortical perfusion: -0.62 (-1.02, -0.22), P = 0.006, and increased renal cortex adenosine levels: 2.32 (0.83, 3.8), P = 0.0059. These changes were accompanied by significant reduction in creatinine clearance at 1.5 h postintervention, MD 95% CI; -51.7 (-99.7, -3.7), P = 0.037, and at 24 h, MD (95% CI): -47.3 (-87.7, -7.6), P = 0.023, and proteinuria immediately postintervention MD (95% CI): 18.79 (2.17, 35.4), P = 0.03 vs. sham. In our experimental CPB model, endothelial injury was associated with loss of autoregulation, increase in microvascular permeability, and reduced glomerular filtration. Interventions that promote endothelial homeostasis may have clinical utility in the prevention of postcardiac surgery AKI.
急性肾损伤（AKI）是心脏手术的常见并发症；然而，这种疾病的表型定义不明确。本研究旨在描述体外循环（CPB）后 AKI 相关的内皮结构和功能变化。成年猪（n=16）随机分为以下两组（每组 n=8）：组 1：假手术，颈部解剖术，全身麻醉 2.5 小时；组 2：CPB，CPB 2.5 小时。CPB 导致内皮糖萼侧链特定糖胺聚糖表位耗尽：多利士比弗洛根凝集素：平均差异（MD）[95%置信区间（CI）]，P 值：-0.26（-0.42，-0.09），P=0.0024，麦胚凝集素：-0.83（-1.2，-0.38），P=0.0005，和荆豆凝集素 1：-0.25（-0.49，-0.009），P=0.041；内皮膜蛋白：血栓调节蛋白：-3.13（-5.6，-0.65），P=0.02；和黏附连接：VE-钙粘蛋白：-1.06（-1.98，-0.145），P=0.02。CPB 还导致皮质微血管灌注减少：-0.62（-1.02，-0.22），P=0.006，和肾皮质腺苷水平升高：2.32（0.83，3.8），P=0.0059。这些变化伴随着干预后 1.5 小时肌酐清除率显著降低，MD 95%CI：-51.7（-99.7，-3.7），P=0.037，和 24 小时，MD（95%CI）：-47.3（-87.7，-7.6），P=0.023，和蛋白尿即刻，MD（95%CI）：18.79（2.17，35.4），P=0.03 与假手术相比。在我们的实验 CPB 模型中，内皮损伤与自动调节丧失、微血管通透性增加和肾小球滤过率降低有关。促进内皮稳态的干预措施可能在预防心脏手术后 AKI 方面具有临床应用价值。
