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| Developing a rat model of dilated cardiomyopathy with improved survival |
| Li-juan Shen, Shu Lu, Yong-hua Zhou, Lan Li, Qing-min Xing, Yong-liang Xu |
| Wuxi Hospital of Traditional Chinese Medicine, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi 214071, China; Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, Jiangsu Provincial Key Laboratory on Molecular Biology of Parasites, Jiangsu Provincial Key Subject on Parasitic Diseases, Wuxi 214064, China; Department of Ultrasonography, Wuxi Hospital of Traditional Chinese Medicine, Wuxi Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi 214071, China |
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Abstract To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin (Dox) under the same cumulative dose (12 mg/kg), and establish a rat dilated cardiomyopathy model with improved survival, a total of 150 Sprague-Dawley (SD) rats were divided into three groups: a control group, administered with normal saline; a Dox 1 group, administration twice a week at 1 mg/kg; a Dox 2, administration once a week at 2 mg/kg. Mortality rates in the Dox 1 and Dox 2 groups were 22% and 48%, respectively (P<0.05). As shown by echocardiography, both Dox groups exhibited significant chamber dilatation and reduced cardiac function (all P<0.05 vs. control). Plasma brain natriuretic peptide and C-reactive protein concentrations were significantly increased (P<0.05) with both Dox regimens. The concentrations of Caspase-3 in myocardial tissues of rats significantly increased in both doxorubicin regimens. Myocardial metabolism imaging by histology and 18F-fluoro-deoxyglucose-positron emission tomography (18FDG-PET) both revealed decreased myocardial viability and necrosis, and even interstitial fibrosis, in left ventricles (LVs) in both Dox groups. Serum creatinine and aspartate aminotransferase concentrations were significantly higher in the Dox 2 model than in the Dox 1 model. Doxorubicin given at both regimens induced dilated cardiomyopathy, while its administration at lower doses with more frequent infusions reduced the mortality rate.
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Received: 08 June 2016
Published: 05 December 2016
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