Surgery and Abdominal Transplant Unit, University Clinics Saint Luc, Université Catholique de Louvain, Brussels, Belgium.
Pole de Chirurgie Expérimentale et Transplantation, Université Catholique de Louvain, Brussels, Belgium.
Am J Transplant. 2020 Aug;20(8):2030-2043. doi: 10.1111/ajt.15800. Epub 2020 Feb 21.
With oxygenation proposed as a resuscitative measure during hypothermic models of preservation, the aim of this study was to evaluate the optimal start time of oxygenation during continuous hypothermic machine perfusion (HMP). In this porcine ischemia-reperfusion autotransplant model, the left kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia prior to 22 hours of HMP and autotransplantation. Kidneys were randomized to receive 2 hours of oxygenation during HMP either at the start (n = 6), or end of the perfusion (n = 5) and outcomes were compared to standard, nonoxygenated HMP (n = 6) and continuous oxygenated HMP (n = 8). The brief initial and continuous oxygenated HMP groups were associated with superior graft recovery compared to either standard, nonoxygenated HMP or kidneys oxygenated at the end of HMP. This correlated with significant metabolic differences in perfusate (eg, lactate, succinate, flavin mononucleotide) and tissues (eg, succinate, adenosine triphosphate, hypoxia-inducible factor-1α, nuclear factor erythroid 2-related factor 2) suggesting superior mitochondrial preservation with initial oxygenation. Brief initial O uploading during HMP at procurement site might be an easy and effective preservation strategy to maintain aerobic metabolism, protect mitochondria, and achieve an improved early renal graft function compared with standard HMP or oxygen supply shortly at the end of HMP preservation.
在低温保存的模型中,氧合被提议作为复苏措施,本研究旨在评估在连续低温机器灌注(HMP)期间开始氧合的最佳时间。在这种猪缺血再灌注自体移植模型中,±40kg 猪的左肾在接受 22 小时 HMP 和自体移植前经历了 30 分钟的热缺血。肾脏随机接受 2 小时的 HMP 期间氧合,要么在开始时(n=6),要么在灌注结束时(n=5),并与标准非氧合 HMP(n=6)和连续氧合 HMP(n=8)进行比较。短暂的初始和连续氧合 HMP 组与标准非氧合 HMP 或在 HMP 结束时氧合的肾脏相比,移植恢复更好。这与灌流液(例如乳酸盐、琥珀酸盐、黄素单核苷酸)和组织(例如琥珀酸盐、三磷酸腺苷、缺氧诱导因子-1α、核因子红细胞 2 相关因子 2)中的代谢差异显著相关,表明初始氧合时线粒体保存更好。在获取部位的 HMP 期间进行短暂的初始 O 加载可能是一种简单有效的保存策略,可维持需氧代谢、保护线粒体,并与标准 HMP 或 HMP 保存结束时短时间供氧相比,实现早期肾移植功能的改善。