Developing a rat model of dilated cardiomyopathy with improved survival

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 F-fluoro-deoxyglucose-positron emission tomography (FDG-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.

LTBP2 knockdown by siRNA reverses myocardial oxidative stress injury, fibrosis and remodelling during dilated cardiomyopathy

“…The procedures were as follows: rats were intraperitoneally injected with 2.5 mg/kg Doxorubicin once per week for 10 weeks. Transthoracic echocardiography and haemodynamic monitoring were performed to verify whether the rat model with DCM was constructed successfully . After successful establishment of the rat model with DCM, the 50 rats were randomly assigned into a DCM (no treatment), DCM + negative control (NC) (DCM rats injected with 5 µL of LTBP2 negative control siRNA sequence), DCM + si‐LTBP2 (DCM rats injected with 5 µL of si‐LTBP2‐treated cell suspension (20 ng/ml) with a cell concentration of 1 × 10), DCM + PMA (activator of the NF‐κB signalling pathway) (DCM rats injected with 5 µL of PMA‐treated cell suspension (1 µmol/L) at a cell concentration of 1 × 10 5 ) and DCM + si‐LTBP2 + PMA (DCM rats injected with 5 µL of a mixture treated with si‐LTBP2 and PMA (20 ng/mL) groups.…”

Effect of trimetazidine combined with perindopril on NT-proBNP level in rats with dilated cardiomyopathy

“…On the 8th day, DCM models were established in the combination drug group, trimetazidine group and control group rats (23). Adriamycin was injected intraperitoneally at a dose of 1 mg/kg twice per week for 6 weeks.…”

Melatonin attenuates chemical-induced cardiotoxicity

“…These results are in agreement with other research which indicated that caspase-3 activation is elevated during DXR-induced heart failure. 25 –28 Moreover, melatonin protected the heart from myocardial ischemia by down regulating the cleaved caspase-3 expression in this rat model. 28,29…”