Applebaum Y J, Kuvin J, Borman J B, Uretzky G, Chevion M
Lunenfeld's Cardiac Surgery Research Center, Hadassah University Hospital, Jerusalem, Israel.
Free Radic Biol Med. 1990;8(2):133-43. doi: 10.1016/0891-5849(90)90086-x.
The effect of neocuproine on cardiac injury was studied using retrogradely perfused isolated rat hearts in two experimental systems. In the first system, where hydrogen peroxide-induced damage was studied, neocuproine at the range of 40-175 microM provided protection at the level of 70-85%, as demonstrated by the reduced loss in the peak systolic pressure (P), in +dP/dt and in -dP/dt. In the second system, where ischemia/reperfusion-induced arrhythmias were studied, neocuproine (42 microM) provided a marked protection against cardiac injury as demonstrated by the lowering of the incidence in irreversible ventricular fibrillation, by decreasing the duration of ventricular fibrillation and by the concomitant increase of the duration of normal sinus rhythm, and by improving the post-ischemic recovery of P, +dP/dt and -dP/dt. Free radicals have already been implicated as causative agents in cardiac injury resulting from either hydrogen peroxide or ischemia followed by reperfusion. Additionally, iron and copper have already been shown to drastically exacerbate the injurious effects of free radicals. Thus, the results reported here with neocuproine, a highly effective chelator for both iron and copper, as well as with adventitious copper and with the combination of neocuproine and copper, are in accord with the mediatory role of transition metals in enhancing the deleterious effects induced by free radicals.
在两个实验系统中，使用逆行灌注的离体大鼠心脏研究了新亚铜试剂对心脏损伤的影响。在第一个系统中，研究过氧化氢诱导的损伤，40 - 175微摩尔范围内的新亚铜试剂提供了70 - 85%水平的保护，这通过收缩压峰值（P）、+dP/dt和 -dP/dt的损失减少得以证明。在第二个系统中，研究缺血/再灌注诱导的心律失常，新亚铜试剂（42微摩尔）对心脏损伤提供了显著保护，这通过降低不可逆心室颤动的发生率、缩短心室颤动持续时间、同时增加正常窦性心律持续时间以及改善缺血后P、+dP/dt和 -dP/dt的恢复得以证明。自由基已被认为是过氧化氢或缺血再灌注导致心脏损伤的致病因素。此外，铁和铜已被证明会极大地加剧自由基的损伤作用。因此，这里报道的新亚铜试剂（一种对铁和铜都有效的螯合剂）、外加铜以及新亚铜试剂与铜组合的结果，与过渡金属在增强自由基诱导的有害作用中的介导作用一致。
