J Korean Soc Echocardiogr.  2002 Dec;10(2):35-43.

The Relation between Acute Adriamycin induced Cardiomyopathy and Apoptosis in rat : Study using 15 MHz High Frequency Transducer

• Choi YS
• Park CS
• Cho EJ
• Jung HO
• Jeon HK
• Kang JH
• Lee JH
• Youn HJ
• Chae JS
• Kim JH
• Cho KB
• Hong SJ

Abstract

BACKGROUND
Anthracyclines, such as daunorubicin or doxorubicin that are one of the most widely used as chemotherapeutic agents in oncology clinics have the limitation of its usage because of severe cardiotoxicity. Recently the pathogenesis of ischemic cardiomyopathy, ventricular hypertrophy due to hypertension, and heart failure were investigated with the association with programmed cell death, Apoptosis and new pathogenesis of adriamycin induced cardiomyopathy was proposed as apoptosis in many other in vitro studies in addition to the classical free radical mediated mechanism of adriamycin induced cardiomypathy. METHOD: Adriamycin cardiomyopathy was induced in rats by intraperitoneal injection and after transthoracic echocardiographic examination using 15 MHz high frequency transducer for hemodynamic and morphologic change in cardiomyopathy. Histological analysis was performed by immunohistochemical staining for evaluation of apoptotic gene expression. Rats were randomly assigned to adriamycin treated group (n=23) or saline treated group (n=8) and 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. Transthoracic echocardiography with a 15 MHz linear array transducer was performed at baseline and at 3rd weeks additionally to measure hemodynamic and morphologic parameters. And then, rats were sacrificed and histological analyses were performed with light microscope and bax, bcl-2, caspase 3 autoantibody with immunohistochemical staining and also TUNEL assay.
RESULTS
Among 52 rats, 31 rats were survived (57%). 21 rats were from adriamycin treated group and 8 rats were from the saline treated group. On echocardiogrphic examination, fractional shortening, interventricular septal thickness, diastolic left ventricular internal dimension decreased (P<0.05) but these parameter did not decreased in the saline treated group. Cardiomyocyte apoptosis rates in saline vs adriamycin treatment group were 0.12(0.07% vs 0.27(0.08%, 0.06(0.01% vs 0.12(0.06%, 0.01(0.01% vs 0.03(0.01% in bax, caspase 3, and TUNEL assay respectively. All of these results were significantly higher than the those of saline treated group (P<0.05). But bcl-2 positive cell count was not different from the that of saline treated group.
CONCLUSION
Apoptosis might be related to the pathogenesis of early morphologic and hemodynamic changes in adriamycin-induced cardiomyopathy. The high frequency transducer using 15 MHz linear array is useful for the evaluation of early changes of adriamycin-induced cardiac toxicity.

Keyword

Adriamycin induced cardiomyopathy; Apoptosis; 15 MHz transducer

MeSH Terms

Animals
Anthracyclines
Apoptosis*
Body Weight
Cardiomyopathies*
Cardiotoxicity
Caspase 3
Cell Count
Cell Death
Daunorubicin
Doxorubicin*
Echocardiography
Gene Expression
Heart Failure
Hemodynamics
Hypertension
Hypertrophy
In Situ Nick-End Labeling
In Vitro Techniques
Injections, Intraperitoneal
Methods
Myocytes, Cardiac
Rats*
Transducers*
Anthracyclines
Caspase 3
Daunorubicin
Doxorubicin