Department of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
Oxid Med Cell Longev. 2022 Feb 18;2022:1630918. doi: 10.1155/2022/1630918. eCollection 2022.
The impairment of microcirculation is associated with the unfavorable outcome for extracorporeal membrane oxygenation (ECMO) patients. Studies revealed that pulsatile modification improves hemodynamics and attenuates inflammation during ECMO support. However, whether flow pattern impacts microcirculation and endothelial integrity is rarely documented. The objective of this work was to explore how pulsatility affects microcirculation during ECMO.
Canine animal models with cardiac arrest were supported by ECMO, with the i-Cor system used to generate nonpulsatile or pulsatile flow. The sublingual microcirculation parameters were examined using the CytoCam microscope system. The expression of hsa_circ_0007367, a circular RNA, was measured during ECMO support. In vitro validation was performed in pulmonary vascular endothelial cells (PMVECs) exposed to pulsatile or nonpulsatile flow, and the expressions of hsa_circ_0007367, endothelial tight junction markers, endothelial adhesive molecules, endothelial nitric oxide synthases (eNOS), and NF-B signaling activity were analyzed.
The pulsatile modification of ECMO enhanced microcirculatory perfusion, attenuated pulmonary inflammation, and stabilized endothelial integrity in animal models; meanwhile, the expression of hsa_circ_0007367 was significantly upregulated both in animals and PMVECs exposed to pulsatile flow. In particular, upregulation of hsa_circ_0007367 stabilized the expressions of endothelial tight junction markers zonula occludens- (ZO-) 1 and occludin, followed by modulating the endothelial nitric oxide synthases (eNOS) activity and inhibiting the NF-B signaling pathway.
The modification of pulsatility contributes to microcirculatory perfusion and endothelial integrity during ECMO. The expression of hsa_circ_0007367 plays a pivotal role in this protective mechanism.
微循环受损与体外膜肺氧合（ECMO）患者的不良预后相关。研究表明，脉动改良可改善 ECMO 支持期间的血液动力学并减轻炎症。然而，血流模式是否影响微循环和内皮完整性鲜有报道。本研究旨在探讨脉动对 ECMO 期间微循环的影响。
使用 i-Cor 系统产生非脉动或脉动流，对心脏骤停的犬动物模型进行 ECMO 支持。使用 CytoCam 显微镜系统检查舌下微循环参数。在 ECMO 支持期间测量环状 RNA hsa_circ_0007367 的表达。在体外，将肺血管内皮细胞（PMVECs）暴露于脉动或非脉动流中，分析 hsa_circ_0007367 的表达、内皮紧密连接标志物、内皮黏附分子、内皮型一氧化氮合酶（eNOS）和 NF-B 信号活性。
ECMO 的脉动改良增强了动物模型的微循环灌注，减轻了肺炎症，稳定了内皮完整性；同时，hsa_circ_0007367 的表达在动物和暴露于脉动流的 PMVECs 中均显著上调。特别是，hsa_circ_0007367 的上调稳定了内皮紧密连接标志物 ZO-1 和闭锁蛋白的表达，随后调节内皮型一氧化氮合酶（eNOS）活性并抑制 NF-B 信号通路。
脉动改良有助于 ECMO 期间的微循环灌注和内皮完整性。hsa_circ_0007367 的表达在这种保护机制中起关键作用。
