Hoshino T, Maley W R, Bulkley G B, Williams G M
Department of Surgery, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Transplantation. 1988 Feb;45(2):284-9. doi: 10.1097/00007890-198802000-00006.
Postischemic renal failure is a severe problem following cadaveric renal transplantation, especially if the kidney has been harvested from a non-heartbeating donor, and thereby subjected to periods of both warm and cold ischemia. It is well established that a substantial component of postischemic injury is produced by oxygen-derived free radicals generated from xanthine oxidase at reperfusion. However, the clinical potential of free radical ablative therapy is dependent upon the proportion of the total injury caused by this reperfusion mechanism, compared with the proportion resulting from ischemic injury per se. Therefore, we quantitatively evaluated these proportions in porcine kidneys subjected to various periods of warm (renal artery occlusion in situ), cold (harvest, cold preservation, and allotransplantation), and combined warm and cold ischemia. Experiments were paired, one kidney treated with either superoxide dismutase (SOD) or allopurinol for free radical ablation, the contralateral kidney serving as a control. Creatinine clearance (Ccr) was measured separately for each kidney 48 hr after reperfusion. After 1 and 2 hr of warm ischemia, Ccr dropped to 50% and 36% of normal, respectively. This was improved to 110% and 55% when SOD was given into the renal artery at reperfusion. Similarly, after 24 and 48 hr of cold ischemia, kidney function was significantly improved from 30% and 18% to 72% and 47% of normal, respectively, when allopurinol was added to the preservation solution. SOD used at harvest and again at reperfusion was particularly effective following combined warm and cold ischemia, in a situation mimicking the harvest of cadaver kidneys from a non-heartbeating donor. These findings suggest that the ablation of free radical-mediated reperfusion injury may improve posttransplant renal function sufficiently to allow expansion of the cadaveric donor pool to include non-heartbeating donors.
缺血后肾衰竭是尸体肾移植后的一个严重问题，特别是当肾脏取自非心跳供体时，会经历热缺血和冷缺血阶段。众所周知，缺血后损伤的一个重要组成部分是再灌注时黄嘌呤氧化酶产生的氧自由基所致。然而，自由基清除疗法的临床潜力取决于这种再灌注机制造成的损伤在总损伤中所占的比例，与缺血损伤本身所占比例相比。因此，我们对猪肾进行了不同时长的热缺血（原位肾动脉阻断）、冷缺血（摘取、冷藏保存和同种异体移植）以及热缺血与冷缺血联合处理，定量评估了这些比例。实验采用配对设计，一侧肾脏用超氧化物歧化酶（SOD）或别嘌呤醇进行自由基清除处理，对侧肾脏作为对照。再灌注48小时后分别测量每个肾脏的肌酐清除率（Ccr）。热缺血1小时和2小时后，Ccr分别降至正常水平的50%和36%。再灌注时将SOD注入肾动脉后，Ccr分别提高到正常水平的110%和55%。同样，冷缺血24小时和48小时后，当在保存液中加入别嘌呤醇时，肾功能分别从正常水平的30%和18%显著提高到72%和47%。在模拟从非心跳供体摘取尸体肾的情况下，摘取时和再灌注时均使用SOD，在热缺血与冷缺血联合处理后效果尤为显著。这些发现表明，清除自由基介导的再灌注损伤可能足以改善移植后肾功能，从而扩大尸体供体库，将非心跳供体纳入其中。
