Charles University in Prague, Department of Pharmacology and Toxicology, Heyrovského, Hradec Králové, Czech Republic.
Can J Physiol Pharmacol. 2012 Apr;90(4):473-84. doi: 10.1139/y2012-009. Epub 2012 Mar 22.
Positive effects of dexrazoxane (DEX) in anthracycline cardiotoxicity have been mostly assumed to be associated with its iron-chelating properties. However, this explanation has been recently questioned. Iron plays also an important role in the catecholamine cardiotoxicity. Hence in this study, the influence of DEX on a catecholamine model of acute myocardial infarction (100 mg/kg of isoprenaline by subcutaneous injection) was assessed: (i) the effects of an intravenous dose of 20.4 mg/kg were analyzed after 24 h, (ii) the effects were monitored continuously during the first two hours after drug(s) administration to examine the mechanism(s) of cardioprotection. Additional in vitro experiments on iron chelation/reduction and influence on the Fenton chemistry were performed both with isoprenaline/DEX separately and in their combination. DEX partly decreased the mortality, reduced myocardial calcium overload, histological impairment, and peripheral haemodynamic disturbances 24 h after isoprenaline administration. Continuous 2 h experiments showed that DEX did not influence isoprenaline induced atrioventricular blocks and had little effect on the measured haemodynamic parameters. Its protective effects are probably mediated by inhibition of late myocardial impairment and ventricular fibrillation likely due to inhibition of myocardial calcium overload. Complementary in vitro experiments suggested that iron chelation properties of DEX apparently did not play the major role.
地拉佐辛（DEX）在蒽环类药物心脏毒性中的积极作用主要被认为与其螯合铁的特性有关。然而，这种解释最近受到了质疑。铁在儿茶酚胺的心脏毒性中也起着重要作用。因此，在这项研究中，评估了 DEX 对儿茶酚胺诱导的急性心肌梗死模型（皮下注射 100mg/kg 的异丙肾上腺素）的影响：（i）在 24 小时后分析静脉注射 20.4mg/kg 的效果，（ii）在药物给药后前两小时连续监测，以检查心脏保护的机制。分别用异丙肾上腺素/DEX 以及它们的组合进行了铁螯合/还原以及对芬顿化学的影响的额外体外实验。DEX 部分降低了死亡率，减少了心肌钙超载、组织学损伤和外周血液动力学紊乱，在异丙肾上腺素给药 24 小时后。连续 2 小时的实验表明，DEX 不影响异丙肾上腺素引起的房室传导阻滞，对测量的血液动力学参数几乎没有影响。其保护作用可能是通过抑制晚期心肌损伤和室颤来介导的，这可能是由于抑制心肌钙超载所致。补充的体外实验表明，DEX 的铁螯合特性显然没有发挥主要作用。
