Arterial Pulsatility Augments Microcirculatory Perfusion and Maintains the Endothelial Integrity during Extracorporeal Membrane Oxygenation via hsa_circ_0007367 Upregulation in a Canine Model with Cardiac Arrest.

Guanhua Li,Shenyu Zhu,Zhexuan Yu,Fanji Meng,Jianfeng Zeng,Zhixian Tang,Ping Zhu,Fuqiang Liu

doi:10.1155/2022/1630918

Abstract

Background 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. Methods 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-κB signaling activity were analyzed. Results 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-κB signaling pathway. Conclusion 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.

Highlights

Extracorporeal membrane oxygenation (ECMO) is an important device in critical care medicine, especially during the COVID-19 pandemic [1]
extracorporeal membrane oxygenation (ECMO) is so effective that the American Heart Association (AHA) guidelines on cardiopulmonary resuscitation (CPR) highly recommend ECMO in critical patients who are refractory to traditional means of life support [2]
We previously demonstrated that pulsatile modification attenuates systemic inflammatory responses [7] and protects the glycocalyx by maintaining proper pulsatile shear stress [8] when introducing the i-Cor system to ECMO animal models, but the potential mechanism remains poorly understood

Summary

Introduction

Extracorporeal membrane oxygenation (ECMO) is an important device in critical care medicine, especially during the COVID-19 pandemic [1]. The impairment of microcirculation is associated with the unfavorable outcome for extracorporeal membrane oxygenation (ECMO) patients. Canine animal models with cardiac arrest were supported by ECMO, with the i-Cor system used to generate nonpulsatile or pulsatile flow. 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-κB signaling activity were analyzed. The pulsatile modification of ECMO enhanced microcirculatory perfusion, attenuated pulmonary inflammation, and stabilized endothelial integrity in animal models; the expression of hsa_ circ_0007367 was significantly upregulated both in animals and PMVECs exposed to pulsatile flow. 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-κB signaling pathway. The expression of hsa_circ_0007367 plays a pivotal role in this protective mechanism

Objectives

Methods

Results

Conclusion