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在一个转化性离体猪肾模型中,快速采样微透析作为一种用于评估静态冷藏和低温机器灌注期间实质的新型工具。

Rapid sampling microdialysis as a novel tool for parenchyma assessment during static cold storage and hypothermic machine perfusion in a translational ex vivo porcine kidney model.

作者信息

Hamaoui Karim, Gowers Sally, Damji Samir, Rogers Michelle, Leong Chi Leng, Hanna George, Darzi Ara, Boutelle Martyn, Papalois Vassilios

机构信息

Department of Surgery, Imperial College London, London, United Kingdom.

Department of Bioengineering, Imperial College London, London, United Kingdom.

出版信息

J Surg Res. 2016 Jan;200(1):332-45. doi: 10.1016/j.jss.2015.07.004. Epub 2015 Jul 9.

DOI:10.1016/j.jss.2015.07.004
PMID:26323367
Abstract

BACKGROUND

Viability assessment during preservation is imperative to avoid unnecessary discard of marginal organs maximizing graft outcomes in kidney transplantation. To address this need, we have developed a novel system based on a rapid sampling microdialysis (rsMD) analyzer allowing continuous tissue monitoring and measurement of metabolic markers of cell damage. Our aim was to develop a tool that allows for accurate assessment of tissue metabolism and organ viability in the preservation period.

METHODS

Twenty-two porcine kidneys subjected to 15 min of warm ischemia underwent either 24 h of static cold storage (SCS) or 10 h of hypothermic machine perfusion (HMP). After preservation, tissue temperature was allowed to passively increase to ambient temperature as an ischemic challenge. Cortical and medullary metabolism was monitored throughout with online measurements of lactate concentrations made every 60 s.

RESULTS

On commencement of monitoring, lactate concentrations were successfully detected within 15 mins. During the initial 1.5 h, lactate concentrations were similar during SCS (65 μM) and HMP (124 μM, P > 0.05) but lower after 10 h of SCS (SCS: 68 μM versus HMP: 230 μM, P < 0.001). Warming data suggest a resilience of HMP kidneys to subsequent temperature induced ischemia compared to SCS kidneys.

CONCLUSIONS

This preliminary study provides the baseline ischemic profile for porcine kidneys while validating the technique of rsMD as a tool for organ viability assessment during preservation. The data characterize metabolic differences between SCS and HMP preserved allografts and can help elucidate why HMP is clinically superior to SCS allowing development of interventions to augment these benefits.

摘要

背景

在器官保存过程中进行活力评估对于避免不必要地丢弃边缘器官、最大化肾移植的移植物结果至关重要。为满足这一需求,我们开发了一种基于快速采样微透析(rsMD)分析仪的新型系统,该系统能够连续监测组织并测量细胞损伤的代谢标志物。我们的目标是开发一种工具,用于在保存期准确评估组织代谢和器官活力。

方法

对22个经历15分钟热缺血的猪肾进行24小时静态冷藏(SCS)或10小时低温机器灌注(HMP)。保存后,让组织温度被动升至环境温度作为缺血挑战。在此过程中,每隔60秒在线测量乳酸浓度,以监测皮质和髓质的代谢情况。

结果

在监测开始后的15分钟内成功检测到乳酸浓度。在最初的1.5小时内,SCS组(65μM)和HMP组(124μM,P>0.05)的乳酸浓度相似,但在SCS 10小时后较低(SCS:68μM,HMP:230μM,P<0.001)。升温数据表明,与SCS肾相比,HMP肾对随后温度诱导的缺血具有更强的恢复能力。

结论

这项初步研究提供了猪肾的基线缺血特征,同时验证了rsMD技术作为保存期器官活力评估工具的有效性。这些数据表征了SCS和HMP保存的同种异体移植物之间的代谢差异,并有助于阐明为什么HMP在临床上优于SCS,从而有助于开发增强这些益处的干预措施。

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