Simulation of chronic damages to the ultrastructure of cardiomyocytes by dint of anthracycline antitumor antibiotics, which have selective cardiotoxicity effect, allows to estimate the whole range of structural and functional changes, which are developed in these cells, and to determine the nature and extent of their death. Doxorubicin is one of the most effective drugs from this group. The aim of this work is to study the nature and dynamic changes in the ultrastructure of cardiomyocytes in violation of their regenerative capacity as affected by the anthracycline antibiotic– doxorubicin, which has cardiotoxic effects.
We have studied the nature of the intracellular reorganization of ventricular cardiomyocytes of 40rats after acourse of intraperitoneal administration of doxorubicin. Methods of light and electron microscopy of ultrathin sections of the myocardium revealed that doxorubicin cardiomyocytes’ damages are characterized by the following ultrastructural changes: the deformation of the nuclei with the reorganization of the nucleolar apparatus, expansion of perinuclear spaces, diffuse or small pockets of the lysis of myofibrils, expansion of cisterns of the sarcoplasmic reticulum, structural changes of the mitochondria, etc. Terminal stages of such violations include atrophy of cardiomyocytes, their death by apoptosis and resorption by mononuclear cells.
The most significant changes after the administration of doxorubicin are identified in the following compartments of ventricular cardiomyocytes: nuclear, myofibrillar and agranular sarcoplasmic reticulum. In the nuclei we observed segregation of kariolemma, achange in the shape of the nuclei and the marginalization. Cytoskeleton proteins are destroyed, especially desmin, which refers to proteins of intermediate filaments, as well as participates in maintenance of the shape of the nucleus. Nucleolar changes presented the phenomena of fragmentation, correlated with the increasing lysis of myofilaments, the thinning of the myofibrillar bundles, reducing the number of organelles and the strengthening of the auto phagocytosis process.The electron microscopic studies of the ultrastructure of cardiomyocytes have identified several major reasons of violation of contractile activity and reduction of intracellular regeneration processes.
The first cause is the reorganization of the nuclear compartment, which is accompanied by the changes in the size and shape of the nuclei and by their translocation in the subsarcolemmal zone. The second one is aviolation of architectonic, disorganization of myofibrils and thinning of the myofibrillar fibers. The last cause is the alternative changes in the structure of the intercalated disks.