Brown J M, Grosso M A, Whitman G J, Terada L S, Repine J E, Harken A H
Department of Surgery and Medicine, University of Colorado Health Sciences Center, Denver.
Surgery. 1988 Aug;104(2):266-71.
To investigate the mechanism of cardiac ischemia reperfusion injury, we fed rats tungsten (3 weeks) to inhibit molybdenum-dependent oxidase enzymes. Tungsten-treated isolated perfusion hearts (Langendorff, ventricular balloon, 37 degrees C) had negligible xanthine oxidase activity (less than 0.3 vs greater than 8.0 U/gm myocardium) and improved recovery of developed pressure (DP), contractility (+dP/dt), and compliance (-dP/dt) after 20 minutes of global ischemia (37 degrees C) and 40 minutes of reperfusion. Furthermore, the addition of dimethylthiourea, a freely diffusible O2 metabolite scavenger, but not equimolar urea, a non-O2 metabolite scavenger, improved recovery. High-dose urea improved recovery more than control but less than dimethylthiourea. Combining tungsten and equimolar urea improved recovery the same as dimethylthiourea. We conclude that: (1) inhibition of myocardial oxidase enzymes (including xanthine oxidase) improves recovery of ventricular function after ischemia and reperfusion in the isolated rat heart, (2) infusion (during reperfusion) of a permeable O2 metabolite scavenger (dimethylthiourea) but not equimolar urea improves recovery of ventricular function, (3) infusion of higher concentrations of urea improves postischemic function, and (4) myocardial reperfusion injury is distinguishable from ischemic injury.
为了研究心脏缺血再灌注损伤的机制，我们用钨喂养大鼠3周以抑制钼依赖性氧化酶。经钨处理的离体灌注心脏（Langendorff法，心室球囊，37℃）的黄嘌呤氧化酶活性可忽略不计（小于0.3 U/gm心肌，而正常大于8.0 U/gm心肌），并且在37℃下进行20分钟全心缺血和40分钟再灌注后，其舒张末压（DP）、收缩性（+dP/dt）和顺应性（-dP/dt）的恢复情况有所改善。此外，添加可自由扩散的O2代谢产物清除剂二甲基硫脲可改善恢复情况，而等摩尔的非O2代谢产物清除剂尿素则无此作用。高剂量尿素比对照组更能改善恢复情况，但不如二甲基硫脲。联合使用钨和等摩尔尿素与二甲基硫脲改善恢复情况的效果相同。我们得出以下结论：（1）抑制心肌氧化酶（包括黄嘌呤氧化酶）可改善离体大鼠心脏缺血再灌注后心室功能的恢复；（2）在再灌注期间输注可渗透的O2代谢产物清除剂（二甲基硫脲）而非等摩尔尿素可改善心室功能的恢复；（3）输注更高浓度的尿素可改善缺血后功能；（4）心肌再灌注损伤与缺血损伤是有区别的。
