ULTRASTRUCTURAL REORGANIZATION OF THE MYOCARDIUM ON THE 60TH DAY AFTER DOXORUBICIN-INDUCED CARDIOMYOPATHY IN RATS

Background. To assess the cardiotoxic effects of doxorubicin, it is of great importance to elucidate the nature and severity of tissue and cell damage, their ultrastructural changes, as well as to elucidate the features of myocardial remodeling in such conditions. Objective. The aim of the study was a qualitative and quantitative analysis of ultrastructural changes in the myocardium on the 60th day after doxorubicin-induced cardiomyopathy in rats. Material and methods. Cardiomyopathy in rats was induced by doxorubicin given at a cumulative dose of 15 mg/ kg for 14 days. The animals were removed from the experiment on the 60th day after last administered dose of the medicine. An electron microscopic research method was used. Ultrastructural analysis was performed using a JEM- 100 CX microscope, and morphometric evaluation was done using the ImageJ data processing software. Results. Ultrastructural disorders of the myocardium of rats on the 60th day after doxorubicin-induced cardiomyopathy were characterized by: alterative changes of contractile apparatus and nuclear compartment of cardiomyocytes, activation of autophagic and necrotic cell death and compensatory mitochondria hyperplasia with T-system channels dilation; a variety of reactive changes of capillary endothelium in the form of nuclear hypertrophy and organelle hyperplasia in some endothelial cells along with intracellular edema and destruction of organelles in others, which was accompanied by a significant decrease in cross-sectional area of capillaries; activation of fibroblasts with a formation of interstitial and perivascular fibrosis; activation of autophagy processes in cardiomyocytes, fibroblastic cells and capillary endothelium. Conclusions. The established ultrastructural changes in the rat's myocardium on the 60th day after the doxorubicin- induced cardiomyopathy indicate the complex effect of metabolic and angiogenic mechanisms of pathology development. Activation of autophagy processes plays an important role in myocardial reorganization in the late stages of doxorubicin myocardial damage.