Ferrans V J, Clark J R, Zhang J, Yu Z X, Herman E H
Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Tsitologiia. 1997;39(10):928-37.
A review is presented of the various types of cardiotoxicity associated with the clinical use of doxorubicin, a highly effective antineoplastic agent of the anthracycline family. Acute toxicity is related to rapid intravenous administration of the drug and is manifested by vasodilatation, hypotension and cardiac arrhythmias. Subacute toxicity is very uncommon. It develops early in the course of therapy and is characterized by myocarditis and pericarditis. Chronic toxicity is the most common form of doxorubicin-induced cardiac toxicity. It is manifested by chronic dilated cardiomyopathy, which develops late in the course of therapy or shortly after its termination. Morphologic changes are characteristic and consist of myofibrillar loss and cytoplasmic vacuolization (which is due to dilatation of the sarcoplasmic reticulum) of the myocytes. The damaging effects of reactive oxygen species, generated by the interaction of doxorubicin with iron, play a critically important role in the pathogenesis of the chronic cardiotoxicity. Other factors related to this toxicity include inhibition of DNA topoisomerase II, stimulation of certain immune responses and a diversity of other biochemical effects on various cellular organelles. Doxorubicin induces apoptosis in a variety of cell types, but not in cardiac myocytes. The chronic cardiotoxicity of doxorubicin is significantly attenuated by chelation of iron by ICRF-187 (dexrazoxane). A greatly delayed type of doxorubicin cardiotoxicity has been recently found to occur in survivors of childhood cancers who were treated with doxorubicin without any immediate adverse effects, but develop chronic cardiomyopathy at periods of time ranging up to 15 years later. The pathogenesis of this type of toxicity remains to be determined.
本文综述了与蒽环类高效抗肿瘤药物阿霉素临床应用相关的各种心脏毒性类型。急性毒性与药物快速静脉给药有关，表现为血管扩张、低血压和心律失常。亚急性毒性非常罕见。它在治疗过程早期出现，特征为心肌炎和心包炎。慢性毒性是阿霉素所致心脏毒性最常见的形式。表现为慢性扩张型心肌病，在治疗过程后期或治疗结束后不久出现。形态学改变具有特征性，包括心肌细胞肌原纤维丧失和细胞质空泡化（这是由于肌浆网扩张所致）。阿霉素与铁相互作用产生的活性氧的损伤作用在慢性心脏毒性的发病机制中起至关重要的作用。与此毒性相关的其他因素包括抑制DNA拓扑异构酶II、刺激某些免疫反应以及对各种细胞器的多种其他生化作用。阿霉素可诱导多种细胞类型凋亡，但不诱导心肌细胞凋亡。ICRF - 187（右丙亚胺）螯合铁可显著减轻阿霉素的慢性心脏毒性。最近发现，童年癌症幸存者在接受阿霉素治疗时未出现任何即时不良反应，但在长达15年后的一段时间内发生慢性心肌病，会出现一种延迟很久的阿霉素心脏毒性类型。这种毒性类型的发病机制尚待确定。
