Progressive cardiac dysfunction in adriamycin-induced cardiomyopathy rats.
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 15 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.
Teraoka
K
K
Tokyo Medical College, 2nd Department of Internal Medicine, Kunihiko Teraoka, 6-7-1 Nishishinjuku, Shinjuku-ku, 160-0023, Tokyo, Japan. teraoka@tokyo-med.ac.jp
Hirano
M
M
Yamaguchi
K
K
Yamashina
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D002306:Cardiac Volume; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000503:physiopathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000633:toxicity*; D004452:Echocardiography; D007274:Injections, Intraperitoneal; D008297:Male; D009206:Myocardium / Q000473:pathology; D010538:Peritonitis / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000970:Antineoplastic Agents; D004317:Doxorubicin