ULTRASTRUCTURAL ALTERATIONS OF MYOCARDIAL MEMBRANE SYSTEMS INDUCED BY DOXORUBICIN

Abstract

The fine structural changes in membrane systems of cardiac muscle cells in the setting of chronic doxorubicin (DXR) cardiotoxicity were studied by thin section electron microscopy (TSM), the freeze-fracture method and scanning electron microscopy (SEM) using the osmium-dimethyl sulfoxide-osmium (O-D-O) method. Male albino rabbits were treated intravenously with a dose of 2.5 mg/kg of DXR once a week for 5-10 weeks. Five weeks after the initial treatment with DXR, partial dilatation of the sarcoplasmic reticulum (SR) was observed by TSM and SEM. From 8 to 10 weeks after the DXR treatment, marked dilatation of the SR, characteristic of “DXR cardiomyopathy”, was observed by TSM, while three dimensional SR structures showing extensive spherical ballooning could be seen clearly in bold relief using the O-D-O method. From 5 to 10 weeks after the DXR treatment, the density of the intramembranous particles of the SR and the sarcolemma were decreased in the degenerated cardiac muscle cells. These changes may be responsible for the dysfunction of membrane systems of cardiac muscle cells seen in “DXR cardiomyopathy”.