THE HIGH-INCIDENCE OF ATRIAL THROMBOSIS IN MICE GIVEN DOXORUBICIN

被引:21
作者
FUJIHIRA, S
YAMAMOTO, T
MATSUMOTO, M
YOSHIZAWA, K
OISHI, Y
FUJII, T
NOGUCHI, H
MORI, H
机构
[1] Product Development Laboratories, Fujisawa Pharmaceutical Co. Ltd., Kashima 2-1-6, Yodogawa-ku
[2] Department of Pathology, Osaka Medical College, Daigaku-machi 2-7
关键词
CARDIAC MUSCLE DAMAGE; ELECTRON MICROSCOPY; VACUOLIZATION OF MYOCYTES; DECREASED SPONTANEOUS MOTILITY; PLEURAL EFFUSION; SUBCUTANEOUS EDEMA; FIBRIN; SMALL-ANIMAL MODEL;
D O I
10.1177/019262339302100403
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Doxorubicin (DX)-treated mice represent an animal model for studying new drugs for heart disease. Coincidentally, in the collection of damaged myocardial tissue, thrombosis was detected in the atrium. The incidence reached 75% in mice given 4 mg/kg DX iv 10 times. They were white thrombi consisting of the fibrin, platelets, and neutrophils. Cardiac muscle damage was more prominent in the atria than in the ventricles. Light microscopically, vacuolization and degeneration of atrial myocytes and interstitial inflammatory cell infiltration were observed. Electron microscopy revealed dilatation of the sarcoplasmic reticulum and an increase in number of normal and/or degenerate mitochondria. Inflammation extended from the cardiac muscle to the endocardium. The cause of atrial thrombosis in DX-treated mice is unknown but may relate to endocardial damage and changes of blood flow in the atrium secondary to cardiac muscle damage. DX-treated mice could serve as an experimental animal model for the evaluation of efficacy and toxicity of antithrombotic or antiplatelet drugs.
引用
收藏
页码:362 / 368
页数:7
相关论文
共 19 条
[1]  
Bertazzoli C., Bellini O., Magrini U., Tosana M.G., Quantitative experimental evaluation of adriamycin cardiotoxicity in the mouse, Cancer Treat. Rep., 63, pp. 1877-1883, (1979)
[2]  
Daikoku U., Miyazaki E., Hara T., Hatano M., Shimizu M., Chronic toxicity study of adriamycin hydrochloride, Med. Treat., 6, pp. 1093-1151, (1973)
[3]  
Didisheim P., Animal models useful in the study of thrombosis and antithrombotic agents, Progress in Hemostasis and Thrombosis, 1, pp. 165-197, (1972)
[4]  
Farris E.J., Yeakel E.H., Seitner M.M., Ossifying cartilage and thrombi in the hearts of rats, Am. J. Pathol., 22, pp. 613-619, (1946)
[5]  
Frith C.H., Highman B., Burger G., Scheldon W.D., Spontaneous lesions in virgin and retired breeder BALB/c and C57BL/6 mice, Lab. Anim. Sci., 33, pp. 273-286, (1983)
[6]  
Gottlieb J.A., Lefrac E.A., O'Bryan R.M., Burgess M.A., Fatal adriamycin cardiomyopathy: Prevention by dose limitation, Proc. Am. Assoc. Cancer Res., 14, (1973)
[7]  
Greaves P., Cardiac thrombosis, Histopathology of Preclinical Toxicity Studies
[8]  
Interpretation and Relevance in Drug Safety Evaluation., pp. 247-248, (1990)
[9]  
Guideline for animal experimentation, Exp. Anim., 36, pp. 285-288, (1987)
[10]  
Jubb K.V.F., Kennedy P.C., Palmer N., Lesions of blood vessel and circulatory disturbance, Pathology of Domestic Animals, 1, pp. 238-242, (1970)