Increase in endothelial microparticles is negatively correlated with decrease in renal microperfusion in septic rats

Abstract

Introduction

Endothelial dysfunction is an important pathophysiological mechanism of septic acute kidney injury, and endothelial microparticles (EMPs) can directly reflect the endothelial damage. However, the relationship between EMPs and renal microperfusion remains unclear. In this study, contrast-enhanced ultrasound (CEUS) imaging and side-stream dark field imaging were used to evaluate the renal microcirculatory perfusion in septic rats.

Methods

A cecal ligation and puncture model was established for inducing septic kidney injury in Sprague-Dawley rats. Later, the changes in mean arterial pressure (MAP), lactate level, renal artery blood flow (RBF) and mean renal artery velocity were measured. Flow cytometry was conducted to measure EMPs, CEUS imaging was performed to evaluate cortical and medullary perfusion enhancement, and side-stream dark-field imaging was carried out to detect the perfused small vessel density (PVD) and microvascular flow index of the renal cortex.

Results

In the sepsis group, EMPs and lactate levels increased at 12 h, macrohemodynamics (MAP and RBF) did not change, and the mean artery velocity (547.76 ± 28.40 mm/s) increased compared with the sham group (421.78 ± 34.58 mm/s). Meanwhile, cortical peak echointensity (PE), medullary PE, PVD, and microvascular flow index (MFI) decreased at 12 h. The decreases in pulsatility index (PI) and resistance index (RI) suggested the damage of vascular appearance. The pathological results revealed erythrocyte stasis in the capillaries. At 24 h, macrodynamics decreased compared with that at 12 h. The EMPs and lactate levels reached a peak at 24 h. Glomerular vascular endothelium was locally thickened. Moreover, EMPs were negatively correlated with the decreased renal microcirculatory perfusion.

Conclusions

This study shows that endothelial microparticles (EMPs) are closely associated with renal microcirculatory dysfunction in septic acute kidney injury (S-AKI). CEUS can sensitively reflect changes in renal microperfusion, providing earlier indications of kidney injury compared to macrocirculatory changes, and holds potential for early diagnosis of S-AKI.