Comparative Medicine Lab, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Artif Organs. 2024 Apr;48(4):347-355. doi: 10.1111/aor.14675. Epub 2023 Nov 14.
Validated quantitative biomarkers for assessment of renal graft function during normothermic machine perfusion (NMP) conditions are lacking. The aim of this project was to quantify cortex microperfusion during ex vivo kidney perfusion using laser speckle contrast imaging (LSCI), and to evaluate the sensitivity of LSCI when measuring different levels of renal perfusion. Furthermore, we aimed to introduce LSCI measurements during NMP in differentially damaged kidneys.
Eleven porcine kidneys were nephrectomized and perfused ex vivo. Cortex microperfusion was simultaneously monitored using LSCI. First, a flow experiment examined the relationship between changes in delivered renal flow and corresponding changes in LSCI-derived cortex microperfusion. Second, renal cortical perfusion was reduced stepwise by introducing a microembolization model. Finally, LSCI was applied for measuring renal cortex microperfusion in kidneys exposed to minimal damage or 2 h warm ischemia (WI).
Cortex microperfusion was calculated from the LSCI-obtained data. The flow experiment resulted in relatively minor changes in cortex microperfusion compared to the pump-induced changes in total renal flow. Based on stepwise injections of microspheres, we observed different levels of cortex microperfusion that correlated with administrated microsphere dosages (r = 0.95-0.99). We found no difference in LSCI measured cortex microperfusion between the kidneys exposed to minimal damage (renal cortex blood flow index, rcBFI = 2090-2600) and 2 h WI (rcBFI = 2189-2540).
Based on this preliminary study, we demonstrated the feasibility of LSCI in quantifying cortex microperfusion during ex vivo perfusion. Furthermore, based on LSCI-measurements, cortical microperfusion was similar in kidneys exposed to minimal and 2 h WI.
在常温机器灌注(NMP)条件下,缺乏用于评估肾移植功能的经过验证的定量生物标志物。本项目的目的是使用激光散斑对比成像(LSCI)定量测量离体肾脏灌注过程中的皮质微循环,并评估 LSCI 在测量不同水平肾灌注时的灵敏度。此外,我们旨在在不同受损的肾脏中引入 NMP 期间的 LSCI 测量。
11 头猪的肾脏被切除并进行离体灌注。同时使用 LSCI 对皮质微循环进行同步监测。首先,流量实验研究了输送肾流量的变化与 LSCI 衍生的皮质微循环变化之间的关系。其次,通过引入微栓塞模型逐渐降低肾皮质灌注。最后,将 LSCI 应用于测量受最小损伤或 2 小时热缺血(WI)暴露的肾脏皮质微循环。
从 LSCI 获得的数据中计算出皮质微循环。与泵引起的总肾流量变化相比,流量实验导致皮质微循环的相对较小变化。基于逐步注入微球,我们观察到不同水平的皮质微循环与给药的微球剂量相关(r=0.95-0.99)。我们发现暴露于最小损伤的肾脏(肾皮质血流指数,rcBFI=2090-2600)和 2 小时 WI(rcBFI=2189-2540)之间,LSCI 测量的皮质微循环没有差异。
基于这项初步研究,我们证明了 LSCI 在定量测量离体灌注期间皮质微循环的可行性。此外,基于 LSCI 测量,暴露于最小和 2 小时 WI 的肾脏的皮质微灌注相似。