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KMID : 0376219840210030601
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Chonnam Medical Journal
1984 Volume.21 No. 3 p.601 ~ p.621
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Electron Microscopic Study of Adriamycin-Induced Cardiomyopathy in the Rabbit.
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趙炳權/Cho, Byung-Kwun
朴玉圭/李珉徹/尹康爀/Park, Ok-Kyu/Lee, Min-Cheol/Yoon, Kang-Hyuk
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Abstract
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The anthracycline antibiotic, adriamycin, is one of the most powerful and promising broad-spectrum chemotherapeutic agent against malignant tumors. But adriamycin exhibited several undesirable toxic side effects, the most severe of which was a cardio toxicity that had resulted in the establishment of maximal recommanded total drug doses.
To study the cardiotoxic effects of single and divided high doses of adriamycin, a model of animal experiment was performed in the adult male rabbits. Adriamycin at doses of 1.3mg/kg x 15, 6.7 mg/ kg x 3 and 20 mg/ kg x 1 were treated every other days via ear vein, total cumulative doses of 20 mg/ kg, in each group of rabbits which were sacrificed at seventh day after last treatment. Light and electron microscopic evaluations were done at left ventricular myocardium in the rabbits.
The results were as follows.
1. Cardiomyopathy was more evident at base and middle area of ventricular wall than apical region.
2. In the light microscopic observations, myocardial lesions were composed of vacuolation of cardiac myocytes, loss of cross striations, homogenization of the sarcoplasm, interstitial edema, noninflammatory focal myocytolysis accompanied by interstitial fibroblastic infiltrations and myofiber atrophy. These lesions did not occur synchronously in all affected myocytes, and exhibited different evolutionary stages. The most predominent myocardial lesions were observed in experimental group of 6.7 mg/ kg x3.
3. In the electron microscopic study, above light microscopic findings were observed as dilatation of sarcoplasmic reticulum, dissociation of sarcomeres due to fragmentation and loss of myofilaments, degeneration and destruction of mitochondria and formation of dense and myeloid bodies, formaton of thick and thin nuclear filaments, and peripheral clumping of chromatin. The sum of these changes were observed as so called "adria cells", but which were not appeared in experimental group of 20 mg/ kg x 1. At last, nuclear pyknosis and myocytolysis with fibroblast proliferation were noted. These lesions were most prominent in experimental group of 6.7 mg / kg x 3.
From these results it might be concluded that adriamycin-induced cardiomyopathy in the rabbits were most prominent in subacute toxicity groups, and that lesions might be resulted from nuclear and mitochondrial damages.
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