Karck M, Tanaka S, Berenshtein E, Sturm C, Haverich A, Chevion M
Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Carl Neuberg Str 1, 30623 Hannover, Federal Republic of Germany.
J Thorac Cardiovasc Surg. 2001 Jun;121(6):1169-78. doi: 10.1067/mtc.2001.113325.
Traces of redox-active transition metals such as iron and copper play an important role in free radical formation during postischemic reperfusion of the heart. Two studies were conducted to assess the efficacy of the complexes of desferrioxamine with zinc or gallium to prevent this aspect of reperfusion injury.
In study I, isolated working rat hearts (n = 96) were subjected to 2 hours of hypothermic arrest at 10 degrees C induced by use of St Thomas' Hospital cardioplegic solution II supplemented with desferrioxamine, zinc-histidinate, zinc-desferrioxamine, gallium-nitrate, or gallium-desferrioxamine. In study II, isolated nonworking rat hearts (n = 23) were subjected to normothermic regional (10 minutes) or global (35 minutes) unprotected ischemia. In this study, the perfusate was supplemented with gallium-desferrioxamine during preischemic and postischemic periods.
In study I, the addition of desferrioxamine, zinc-histidinate, or gallium-nitrate to St Thomas' Hospital solution II improved postischemic aortic flow recovery. When the binary complexes zinc-desferrioxamine or gallium-desferrioxamine were added, however, functional recovery was further enhanced significantly. In study II, high-performance liquid chromatography analyses of tissue from postischemic hearts exposed to unsupplemented perfusate revealed a marked increase of malondialdehydes. In hearts perfused with perfusate supplemented with gallium-desferrioxamine, however, tissue malondialdehyde concentrations were significantly smaller, indicating reduced free radical formation.
The data suggest synergistic protection by the complexes of the iron chelator desferrioxamine with zinc or gallium. The single components neutralize transition metals by 2 different but complementary push-and-pull mechanisms, thereby leading to an inhibition of metal-mediated site-specific free radical formation and improvement of postischemic cardiac function.
铁和铜等具有氧化还原活性的过渡金属痕迹在心脏缺血后再灌注期间的自由基形成过程中发挥重要作用。开展了两项研究以评估去铁胺与锌或镓的络合物预防再灌注损伤这一方面的效果。
在研究I中，使用补充了去铁胺、组氨酸锌、锌-去铁胺、硝酸镓或镓-去铁胺的圣托马斯医院心脏停搏液II，将离体工作大鼠心脏（n = 96）在10℃下进行2小时低温停搏。在研究II中，将离体非工作大鼠心脏（n = 23）进行常温局部（10分钟）或全心（35分钟）无保护缺血。在本研究中，在缺血前期和缺血后期向灌注液中添加镓-去铁胺。
在研究I中，向圣托马斯医院溶液II中添加去铁胺、组氨酸锌或硝酸镓可改善缺血后主动脉血流恢复。然而，当添加二元络合物锌-去铁胺或镓-去铁胺时，功能恢复进一步显著增强。在研究II中，对暴露于未补充灌注液的缺血后心脏组织进行高效液相色谱分析，结果显示丙二醛显著增加。然而，在灌注补充了镓-去铁胺的灌注液的心脏中，组织丙二醛浓度显著较小，表明自由基形成减少。
数据表明铁螯合剂去铁胺与锌或镓的络合物具有协同保护作用。单一成分通过两种不同但互补的推拉机制中和过渡金属，从而抑制金属介导的位点特异性自由基形成并改善缺血后心脏功能。
