Harper Simon J F, Hosgood Sarah A, Waller Helen L, Yang Bin, Kay Mark D, Goncalves Ines, Nicholson Michael L
Transplantation Department, University of Leicester, Leicester General Hospital, Leicester, United Kingdom.
Transplantation. 2008 Aug 15;86(3):445-51. doi: 10.1097/TP.0b013e31817fe0cd.
The precise effect of warm ischemia on renal allograft function remains unclear and leads to variable warm ischemic time (WIT) limits advocated by transplant programs. This study aims to investigate the relationship between WIT, renal ischemia reperfusion injury, and graft function using a hemoperfused kidney model.
Porcine kidneys were perfused with normothermic blood on an isolated organ perfusion system. Kidneys were divided into four groups (n=6) and subjected to 7, 15, 25, and 40 min WIT. Physiological parameters were measured throughout the 6 hr perfusion period. Serum, tissue, and urine samples were analyzed for histological and biochemical markers of ischemia reperfusion injury.
Creatinine clearance, urine output, renal hemodynamics, and oxygen consumption deteriorated proportionally with increasing WIT. A significant increase in plasma carbonyl levels during perfusion was seen after 25 and 40 min WIT only. Plasma 8-isoprostane levels were higher after 40 min WIT (2.5+/-1.6) vs. 7, 15, and 25 min WIT (0.65+/-0.43, 0.25+/-0.12, and 0.62+/-0.21, respectively; P<0.05). A negative correlation was shown between urine output and plasma carbonyls (r=-0.415, P<0.05) and between 8-isoprostane levels and creatinine clearance (r=-0.649, P<0.005). Caspase-3 activity was significantly higher after 7 min WIT compared with the other groups, correlating positively with creatinine clearance, urine output, and renal blood flow.
The isolated organ perfusion system successfully delineated a clear WIT-dependent variation in renal function which correlated accurately with oxidative injury markers. This model may represent a clinically applicable tool for assessing graft viability.
热缺血对肾移植功能的确切影响仍不清楚，这导致不同移植项目所倡导的热缺血时间（WIT）限制存在差异。本研究旨在使用血液灌注肾模型研究WIT、肾缺血再灌注损伤和移植肾功能之间的关系。
在离体器官灌注系统上用常温血液灌注猪肾。将肾脏分为四组（n = 6），分别给予7、15、25和40分钟的WIT。在整个6小时灌注期内测量生理参数。分析血清、组织和尿液样本中的缺血再灌注损伤组织学和生化标志物。
肌酐清除率、尿量、肾血流动力学和氧消耗随WIT增加而成比例恶化。仅在25分钟和40分钟WIT后，灌注期间血浆羰基水平显著升高。40分钟WIT后的血浆8-异前列腺素水平（2.5±1.6）高于7、15和25分钟WIT后的水平（分别为0.65±0.43、0.25±0.12和0.62±0.21；P<0.05）。尿量与血浆羰基之间呈负相关（r = -0.415，P<0.05），8-异前列腺素水平与肌酐清除率之间呈负相关（r = -0.649，P<0.005）。与其他组相比，7分钟WIT后半胱天冬酶-3活性显著更高，与肌酐清除率、尿量和肾血流量呈正相关。
离体器官灌注系统成功地描绘了肾功能中明显的WIT依赖性变化，这与氧化损伤标志物准确相关。该模型可能代表一种评估移植物活力的临床适用工具。
