Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle dogs
Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle dogs
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DOI：
10.1023/a:1006088907271
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发表时间：
1998-01-01
影响因子：
3.4
通讯作者：
Suzuki, T
中科院分区：
文献类型：
--
作者：
Noda, T;Watanabe, T;Suzuki, T
本研究旨在调查 SM-5887 的慢性心脏毒性潜力以及 SM-5887 对阿霉素预先诱导的比格犬低度心脏毒性的可能恶化作用。在长期治疗中，每种性别的小猎犬每 3 周静脉注射一次亚致死剂量的阿霉素 (1.5 mg/kg) 或 SM-5887 (2.5 mg/kg)。第九次给药后3周终止实验。接受超过六个疗程的多柔比星的动物表现出心电图（ECG）变化、血压下降和高度组织病理学心肌病，而在施用SM-5887后最终处死的动物没有表现出心电图、血压和组织病理学检查的任何变化。为了检查 SM-5887 可能恶化的心脏毒性作用，通过四个疗程的阿霉素（1.5 mg/kg）在狗中诱发低度心肌病。预处理九周后，每三周给狗注射四个疗程的阿霉素（1.5 毫克/公斤）或 SM-5887（2.5 毫克/公斤）。额外的阿霉素治疗增强了低度心脏毒性变化。相反，SM-5887 治疗并未使心肌病的分级进展。总之，SM-5887 不具有任何潜在的慢性心脏毒性，也不会对阿霉素诱导的狗心脏毒性产生恶化作用。
This study was designed to investigate the chronic cardiotoxic potential of SM-5887 and a possible deteriorating effect of SM-5887 on low-grade cardiotoxicity pre-induced by doxorubicin in beagle dogs. In the chronic treatment, beagle dogs of each sex were given intravenously once every 3 weeks, either a sublethal dose of doxorubicin (1.5 mg/kg) or SM-5887 (2.5 mg/kg). The experiment was terminated 3 weeks after the ninth dosing. Animals which received over six courses of doxorubicin demonstrated the electrocardiogram (ECG) changes, decrease of blood pressure and high-grade histopathological cardiomyopathy, while animals which were terminally sacrificed after the SM-5887 administration did not show any changes in ECG, blood pressure and histopathological examinations. To examine a possibly deteriorating cardiotoxic effect of SM-5887, low-grade cardiomyopathy was induced in dogs by four courses of doxorubicin (1.5 mg/kg). Nine weeks after pre-treatment, dogs were given four courses of either doxorubicin (1.5 mg/kg) or SM-5887 (2.5 mg/kg) once every 3 weeks. The low-grade cardiotoxic changes were enhanced by the additional doxorubicin treatment. On the contrary, the SM-5887 treatment did not progress the grade of cardiomyopathy. In conclusion, SM-5887 does not have any potential of chronic cardiotoxicity and deteriorating effect on doxorubicin-induced cardiotoxicity in dogs.