Effect and mechanism of Qishen Yiqi Pills on adriamycin- induced cardiomyopathy in mice / 中国天然药物

AIM@#To study the effect and probable mechanism of Qishen Yiqi Pills on adriamycin (ADR)-induced cardiomyopathy in mice.@*METHODS@#Sixty-four mice were randomly divided into (1) the ADR group: saline (1 mL/100 g) administered every day by intragavage, ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks; (2) the ADR + Qishen Yiqi Pills I group: ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks, and at the beginning of the third week Qishen Yiqi Pills (3.5 mg/100 g) administered by intragavage every day for four weeks; (3) the ADR + Qishen Yiqi Pills II group: ADR (4 mg·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks, and at the same time Qishen Yiqi Pills (3.5 mg/100 g) administered by intragavage every day for four weeks; (4) the control group: saline (1 mL/100 g) administered every day by intragavage, saline (1 mL·kg(-1)) administered to each mouse by intraperitoneal injection twice a week for four weeks. Six weeks later, cardiac function, myocardial pathology, and expression of Bcl-2 and Bax were evaluated.@*RESULTS@#1. The left ventricular diastolic diameter and the left ventricular systolic diameter were significantly increased (P < 0.05) and the left ventricular ejection fraction was significantly decreased (P < 0.05) in the ADR group, and the cardiac function of both the ADR + Qishen Yiqi Pills I group and the ADR + Qishen Yiqi Pills II group improved. 2. Myocardial morphologic observation showed that the myocardial fibers were disordered, there was cell edema, and gap widening in the ADR group. The degree of myocardial cell injury was reduced in the ADR + Qishen Yiqi Pills I group and ADR + Qishen Yiqi Pills II group compared with the ADR group. 3. The expression of Bax in the ADR group was significantly up-regulated, and the expression of Bcl-2 was significantly downregulated in the ADR group compared with the ADR + Qishen Yiqi Pills I group, the ADR + Qishen Yiqi Pills II group, and the control group (P < 0.05).@*CONCLUSIONS@#Qishen Yiqi Pills can effectively improve the cardiac function of ADR-induced cardiomyopathy, and the earlier it is used is better. The probable mechanism of action may be the inhibition of the apoptosis of myocardial cells.

Transthoracic Echocardiographic Assessment of Adriamycin-induced Cardiomyopathy in Rats with a 15 MHz Transducer

BACKGROUND: Adriamycin (doxorubicin) is one of the widely used drugs in the treatment of a variety of solid and hematologic malignancies. However, the adriamycin-induced cardiomyopathy limits the prolonged use of this effective drug. Transthoracic echocardiography is the excellent tool in early detection and follow-up studies of adriamycin-induced cardiomyopathy. The aim of this study was to assess the cardiac function and morphology using a 15 MHz high-frequency imaging in rats. METHODS: Adriamycin was administrated intraperitoneally by six equal injections at a dose of 2.5 mg/kg over a period of 2 weeks for total cumulative dose of 15 mg/kg body weight in 12 male Sprague-Dawley rats (weight 367+/-39 g). Transthoracic echocardiography with a 15 MHz linear-array transducer was performed at baseline and additionally at 3 weeks to measure the left ventricular wall thickness and dimension from the parasternal short axis view with 2D guided M-mode and pulsed Doppler signals of mitral inflow. Within 2 days of echocardiography, the heart was harvested for electron microscopic evaluation after potassium-induced cardiac arrest. RESULTS: 1) The mortality rate during the experimental period was 0%. 2) Transthoracic echocardiography provided adequate 2D guided M-mode images and pulsed Doppler signals of mitral inflow in all rats. 3) In follow-up echocardiography, pericardial effusion was detected in 7out of 12 rats (58%). 4) Compared to baseline, end-diastolic dimensions were increased from 7.01+/-0.69 to 7.74+/-1.25 mm (p<0.001), end-systolic dimensions were increased from 4.13+/-0.69 to 5.22+/-1.12 mm (p<0.05), and interventricular septal and posterior wall thickness at end-systole and end-diastole were significantly decreased (p<0.05, respectively). 5) Fractional shortening was decreased from 43.0+/-6.8 to 32.7+/-8.0%, compared to baseline (p<0.05). 6) E/A ratio of mitral inflow changed significantly from 1.63+/-0.36 to 2.78+/-1.0, compared to baseline (p<0.05). CONCLUSION: Adriamycin administration at total cumulative dose of 15 mg/kg body weight over 2 weeks creates a reliable model of non-ischemic dilated cardiomyopathy in rats with a high success rate. Transthoracic echocardiography using a 15 MHz transducer provides adequate images for assessing the cardiac function and morphology in follow-up studies in adriamycin-induced cardiomyopathy of rats. These results suggest that transthoracic echocardiography using a 15 MHz Transducer is a promising tool for an assessment of adriamycin-induced cardiomyopathy in small animals.