Zeltcer G, Berenshtein E, Samuni A, Chevion M
Department of Cellular Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Free Radic Res. 1997 Dec;27(6):627-35. doi: 10.3109/10715769709097866.
The effects of Cu(II) and the stable nitroxide radical 4-OH-2, 2, 6, 6-tetramethyl-piperidine-1-oxyl (TPL) on reperfusion injury following global myocardial ischemia have been studied using the isolated rat heart model in the Langendorff configuration. Hearts were equilibrated with Krebs-Henseleit buffer (KH-buffer) for 10 min and subjected to 18 min of normothermic global ischemia. After 20 min reperfusion, hemodynamic parameters recovered as follows: ventricular developed pressure (77%), dP/dt (71%) and -dP/dt (80%), heart rate (91%), and work index (70%). End-diastolic pressure was 16 mm Hg. When 10 microM Cu-nitrilotriacetate or Cu-(histidine)2 was included in the perfusate before, during, and following ischemia, the heart injury was more extensive and the work index only recovered to 17% of the preischemic value. The inclusion of 100 microM TPL during reperfusion abolished the copper-induced sensitization. In the absence of copper, TPL did not provide any protection against ischemia-reperfusion damage to the heart. The inclusion of 100 microM 1,4-dihydroxy-2,2,6,6-tetramethylpiperidine (TPL-H) during reperfusion, partially abolished the copper-induced sensitization. Since conversion between TPL and TPL-H takes place, the fact that both forms provide protection can increase their protective efficacy.
使用Langendorff装置的离体大鼠心脏模型，研究了Cu(II)和稳定的氮氧自由基4-羟基-2,2,6,6-四甲基哌啶-1-氧基(TPL)对全心缺血后再灌注损伤的影响。心脏用Krebs-Henseleit缓冲液(KH缓冲液)平衡10分钟，然后进行18分钟的常温全心缺血。再灌注20分钟后，血流动力学参数恢复如下：心室舒张末压(77%)、dP/dt(71%)和 -dP/dt(80%)、心率(91%)和做功指数(70%)。舒张末压为16 mmHg。当在缺血前、缺血期间和缺血后，灌注液中加入10 μM的次氮基三乙酸铜或Cu-(组氨酸)2时，心脏损伤更广泛，做功指数仅恢复到缺血前值的17%。再灌注期间加入100 μM TPL可消除铜诱导的敏感性增加。在没有铜的情况下，TPL对心脏缺血再灌注损伤没有提供任何保护作用。再灌注期间加入100 μM 1,4-二羟基-2,2,6,6-四甲基哌啶(TPL-H)可部分消除铜诱导的敏感性增加。由于TPL和TPL-H之间会发生转化，两种形式都具有保护作用这一事实可能会提高它们的保护效果。
