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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Dexrazoxane provided moderate protection in a catecholamine model of severe cardiotoxicity
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Dexrazoxane provided moderate protection in a catecholamine model of severe cardiotoxicity

机译:右雷佐生在严重心脏毒性的儿茶酚胺模型中提供了中等程度的保护

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摘要

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.
机译:dexrazoxane(DEX)对蒽环类药物的心脏毒性的积极作用通常被认为与其铁螯合特性有关。但是,这种解释最近受到质疑。铁在儿茶酚胺心脏毒性中也起重要作用。因此,在本研究中,评估了DEX对急性心肌梗塞儿茶酚胺模型(皮下注射100 mg / kg异丙肾上腺素)的影响:(i)24小时后分析了20.4 mg / kg静脉内剂量的影响,(ii)在给药后的前两个小时内连续监测效果,以检查心脏保护的机制。分别使用异丙肾上腺素/ DEX或以其组合方式进行了关于铁螯合/还原以及对芬顿化学的影响的其他体外实验。服用异丙肾上腺素后24小时,DEX可以部分降低死亡率,减少心肌钙超载,组织学损害和周围血流动力学障碍。连续2 h实验表明,DEX不会影响异丙肾上腺素诱导的房室传导阻滞,并且对测量的血流动力学参数影响很小。它的保护作用可能是通过抑制晚期心肌损伤和心室纤颤而介导的,这可能是由于抑制了心肌钙超载所致。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。

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