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

Choi, Joo Yeon; Yoon, Ho Joong; Kang, Jin Hyung; Jeon, Hee Gyung; Lim, Hyo Young; Park, Jee Won; Kim, Hee Yeol; Jung, Wook Sung; Chae, Jang Sung; Kim, Jae Hyung; Choi, Gyu Bo; Hong, Soon Jo

Abstract

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.