Progressive cardiac dysfunction in adriamycin-induced cardiomyopathy rats

Progressive cardiac dysfunction in adriamycin-induced cardiomyopathy rats
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DOI:
10.1016/s1388-9842(00)00111-2
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发表时间:
2000-12-01
影响因子:
18.2
通讯作者:
Yamashina, A
Yamashina, A
中科院分区:
医学1区
文献类型:
--
作者:
Teraoka, K;Hirano, M;Yamashina, A

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心脏毒性是阿霉素治疗癌症的限制因素。我们通过一种可最大程度地降低阿霉素诱导的心肌病大鼠模型中腹膜炎风险的方法施用阿霉素。 60只雄性Wistar大鼠腹腔注射阿霉素1 mg/kg,持续3周1.5次(总剂量15 mg/kg),诱导心肌病模型。 15只对照大鼠接受10ml/kg体重。 3 周内注射 15 次生理盐水。观察动物 12 周并评估死亡率,并在第 4、8 和 12 周时通过超声心动图分析心脏体积和功能。在接受阿霉素治疗的大鼠中,累积死亡率为 35.8%,而在对照组中,没有一只大鼠死亡。 4 周时左心室收缩直径 (LVD) 显着增加(4.5 毫米与 3.3 毫米;P < 0.001)。阿霉素治疗组大鼠的左心室舒张直径 (LVDd) 在 12 周时显着增加(7.9 vs. 7.0 mm;P < 0.01),缩短分数 (FS) 在 8 周时显着下降(33.4% vs. 50.0%;P < 0.01)。这种给药方法似乎可用于研究阿霉素的心脏作用,同时避免通常由腹膜内注射较高单剂量阿霉素引起的腹膜炎的影响。 (C) 2000 年欧洲心脏病学会。版权所有。
Cardiotoxicity is a limiting factor in the treatment of cancer with adriamycin. We administered adriamycin by a method which minimizes the risk of peritonitis in an adriamycin-induced cardiomyopathy rat model. Sixty male Wistar rats were given 1 mg/kg of adriamycin intraperitoneally 1.5 times over a 3-week period (total dose, 15 mg/kg) to induce the cardiomyopathy model. Fifteen control rats received 10 ml/kg body wt. saline 15 times over 3 weeks. The animals were observed for 12 weeks and assessed for mortality, and cardiac volume and function was analyzed by echocardiography at 4, 8, and 12 weeks. In rats treated with adriamycin, the cumulative :mortality was 35.8% while in the controls, none of the rats died. Left ventricular diameter of the systole (LVDs) was significantly increased at 4 weeks (4.5 vs. 3.3 mm; P < 0.001). Left ventricular diameter of the diastole (LVDd) was significantly increased at 12 weeks (7.9 vs. 7.0 mm; P < 0.01) and the % fractional shortening (FS) was significantly decreased at 8 weeks (33.4% vs. 50.0%; P < 0.01) in the adriamycin-treated rats. This administration method appears to be useful for investigating the cardiac effect of adriamycin while avoiding the influence of peritonitis typically caused by an intraperitoneal injection of higher single doses of adriamycin. (C) 2000 European Society of Cardiology. All rights reserved.