Cardiac disease induced by chronic adriamycin administration in dogs and an evaluation of vitamin E and selenium as cardioprotectants.
Cardiac disease induced by chronic adriamycin administration in dogs and an evaluation of vitamin E and selenium as cardioprotectants.
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发表时间：
1980-04
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通讯作者：
J. Vleet;V. Ferrans;Walter;E. Weirich
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作者：
J. Vleet;V. Ferrans;Walter;E. Weirich
通过每周静脉注射（1 mg/kg体重）持续20周（累积剂量400 mg/m2），在三组比格犬中产生慢性阿霉素（ADR）中毒。A组（6只犬）仅接受ADR; B组（6只犬）接受ADR和每周剂量的维生素E（17 mg/kg体重）（以α-生育酚醋酸酯形式）; C组（6只犬）接受ADR和每周剂量的维生素E（与B组相同）和硒（0.06 mg/kg体重，以亚硒酸盐形式）。18只犬均发生ADR诱导的心肌病（CMY），11只犬在第17-20周期间死亡。B组的死亡率最低（2/6），但在死亡犬的存活时间或CMY严重程度方面均未观察到组间差异。心肌病在死亡的狗中比在幸存者中更严重。11只死亡犬中有4只出现充血性心力衰竭伴渗出。心脏组织病理学以心肌细胞空泡变性为特征。心肌损害以左心室和室间隔最重，右心室和左心房居中，右心房最轻。超微结构研究表明，受损心肌细胞的早期改变是肌浆网扩张，形成肌浆空泡。偶见肌原纤维溶解，肌浆网局灶性增生。这项研究表明，狗提供了一个合适的模型，研究慢性ADR心脏毒性在man. The缺乏心脏保护维生素E和硒补充剂未能支持拟议的作用，脂质过氧化损伤的发展中的慢性ADR诱导CMY。
Chronic adriamycin (ADR) intoxication was produced in three groups of beagle dogs by weekly intravenous injections (1 mg/kg body weight) for 20 weeks (cumulative dose 400 mg/sq m). Group A (6 dogs) received ADR only; Group B (6 dogs) were given ADR and weekly doses of vitamin E (17 mg/kg body weight) as alpha-tocopherol acetate; and Group C (6 dogs) received ADR and weekly doses of vitamin E as did Group B and selenium (0.06 mg/kg body weight as selenite). Each of the 18 dogs developed ADR-induced cardiomyopathy (CMY), and death occurred in 11 dogs during Weeks 17-20. Mortality was lowest in Group B (2 of 6), but no differences between groups were seen either in survival time of the dogs that died or in severity of CMY. Cardiomyopathy was more severe in dogs that died than in survivors. Congestive heart failure with transudation was present in 4 of 11 dogs that died. Cardiac histopathology was characterized by vacuolar degeneration of myocytes. Myocardial damage was most severe in the left ventricle and the ventricular septum, intermediate in the right ventricle and the left atrium, and least in the right atrium. Ultrastructural study showed that an early alteration in damaged myocytes was distention of sarcoplasmic reticulum to form sarcoplasmic vacuoles. Occasional damaged fibers had myofibrillar lysis and focal proliferation of sarcoplasmic reticulum. This study demonstrates that the dog offers a suitable model for studies of chronic ADR cardiotoxicity in man. The lack of cardioprotection from vitamin E and selenium supplementation fails to support the proposed role of lipoperoxidative damage in the development of chronic ADR-induced CMY.