Mann Christopher D, Metcalfe Matthew S, Nicholson Michael L
Department of Transplant Surgery, University Hospital of Leicester, Leicester, UK.
J Nephrol. 2009 Jan-Feb;22(1):144-51.
Non-heart-beating donors suffer a period of warm ischaemia (WI) injury, resulting in higher rates of delayed graft function compared with heart-beating donors. Endothelin is believed to play a pathophysiological role in the intense vasospasm associated with WI. This study aimed to investigate renal function using normothermic perfusion and potential therapeutic intervention with endothelin receptor antagonism.
Porcine kidneys, subjected to varying periods of in situ WI (<10, 30 and 60 minutes), underwent normothermic machine perfusion with a perfluorodecalin perfusate. Intrarenal vascular resistance (IRR) was measured throughout perfusion, and urine and perfusate biochemical analysis was performed after 1 and 3 hours. Endothelin receptor antagonism was tested by administration of BQ-123 and BQ-788.
Initial IRR during perfusion increased with WI. IRR reduced to similar levels in all WI groups after 90 minutes of perfusion, but subsequently rose after 150 minutes. BQ-123 considerably increased the initial IRR; however, it abolished the rise seen towards the end of perfusion. BQ-788 had little effect. Renal metabolism and function deteriorated with increasing WI. Perfusion had adverse effects on renal function and metabolism. Endothelin receptor antagonism had little effect on renal function.
This study suggests that ex vivo assessment after normothermic perfusion correlates with warm ischaemic damage. However, endothelin receptor antagonism does not ameliorate the rise in IRR or renal function after kidneys are subjected to a warm ischaemic insult.
非心脏跳动供体经历一段热缺血（WI）损伤期，与心脏跳动供体相比，其移植肾功能延迟发生率更高。内皮素被认为在与WI相关的强烈血管痉挛中起病理生理作用。本研究旨在使用常温灌注及内皮素受体拮抗的潜在治疗干预来研究肾功能。
对经历不同时长原位WI（<10、30和60分钟）的猪肾，使用全氟萘烷灌注液进行常温机器灌注。在整个灌注过程中测量肾内血管阻力（IRR），并在1小时和3小时后进行尿液和灌注液生化分析。通过给予BQ - 123和BQ - 788来测试内皮素受体拮抗作用。
灌注期间的初始IRR随WI时间延长而增加。灌注90分钟后，所有WI组的IRR降至相似水平，但在150分钟后随后又升高。BQ - 123显著增加了初始IRR；然而，它消除了灌注末期出现的升高。BQ - 788作用甚微。随着WI时间延长，肾脏代谢和功能恶化。灌注对肾功能和代谢有不良影响。内皮素受体拮抗对肾功能影响不大。
本研究表明，常温灌注后的体外评估与热缺血损伤相关。然而，内皮素受体拮抗并不能改善肾脏遭受热缺血损伤后的IRR升高或肾功能。
