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We've studied xymedon (30 mg/kg, 12 m) and parmidin (pyridinolcarbamate 30 mg/kg, 12 m.) effects on the development of experimental cholesterol atherosclerosis on rabbits. It was demonstrated that after the use of xymedon aorta damage reduces twice. Xymedon also prevents accumulation of cholesterol and fatty degeneration of the liver. Antiatherogenic effect of xymedon resulted comparable with the effect of parmidin. As it was demonstrated in the present investigation and in the previous ones in contrast to parmidin, xymedon normalizes the lipoproteins balance owing to increase of HDL cholesterol. It also has regenerative activity on endotheliocytes and immunomodulator properties. That can be of great importance for the anti-atherosclerotic effects of the medicine.

Membrane lipid phase has been studied in the sarcoplasmic reticulum (SR) of skeletal muscles, using spin probes. Hypercholesterolemia was found to increase rotation and decrease hydrophobicity of water-soluble probe medium located inside SR vesicles. This is probably indicative of the reduction in SR vesicle membranes. At the same time reduced rotation and increased hydrophobicity and regularity of fat-acid probe micro-environment are observed in hypercholesterolemia, with the differences disappearing nearer to the centre of the membrane. It is suggested that POL activation and cholesterol accumulation in SR membranes in hypercholesterolemia lead to greater density of phospholipid molecules in the membrane.

Light and electron microscopy were employed to study the microcirculatory bed (MCB), intraorganic vessels and lung tissue in rabbits in the first hours (1, 3, 6, 15, 24 and 48 h) after a single administration of cholesterol (ChS) and in the course of the development of experimental atherosclerosis. The MCB demonstrated changes such as dilatation of the venular part, arteriolar constriction, red cell aggregation in capillaries and venules, and stases. At the early stages of experimental atherosclerosis induced by the diet the permeability of the air-blood barrier and the synthesis of lung surfactant were found to be deranged. Vessel-tissue changes in the lungs progressed with an increase in the length of the diet (1-8 months) and were alike the picture seen in chronic nonspecific lung diseases, particularly in what is called senile emphysema. A relationship was established between the degree of changes in the MCB and HCh gravity. Atherosclerotic lesions in the intraorganic arteries occur and progress parallel with the development of this process in the intramural arteries of the myocardium. The data obtained attest to an important role of lipid metabolism disorders in the development of lung pathology and may have a certain significance in specifying the pathogenesis of chronic nonspecific lung diseases, especially.

Structural and functional characteristics of cells involved in collagen synthesis have been studied in experimental hypercholesterolemia in rabbits. Autoradiographic studies, using 3H-proline and 14C-hydroxyproline have demonstrated that collagen synthesis takes place only in the intima in the area of cellular proliferation. At earlier stages of experimental atherosclerosis collagen synthesis predominantly involves synthetic GABA phenotype, while at progressing stages fibroblasts are predominantly involved.

Aortic intima cell proliferation has been studied in 49 rabbits with progressing experimental hypercholesterolemia, using 3H-thymidine. It has been shown that focal cell proliferation is related to infiltration sites of apo-B lipoproteins and can be observed already at pre-lipid stage of atherogenesis. 4 types of proliferating cells involved in the formation of lipid plaques have been identified: endothelial cells, smooth muscle cells, fibroblasts and macrophages, with the latter predominating in the atherosclerotic plaque cover.

Morphometric, histochemical and biochemical methods were used to study the adrenal cortex of rabbits given cholesterol over 60 days' period and killed 5.5 months after the treatment was discontinued. Cholesterol-induced changes were found to undergo considerable regression 5.5 months after the treatment withdrawal.

Functional and structural changes that occurred in the small intestine and liver of rabbits with alimentary hypercholesterolemia have been studied. Maximal rise of peripheral blood cholesterol after a single exposure to cholesterol was coupled with an increased penetration of chylomicrons and low and very low density lipoproteins from the intestine to the circulation. The decrease of cholesterol excretion along the whole length of the small intestine was accompanied by activation of the release of high density lipoproteins into the blood outflowing from the intestine. The decay of chylomicrons in the liver was restricted during the first days of hypercholesterolemia. Cholesterol concentration in the bile was decreased. The microvessels of the small intestine demonstrated the dilatation of the postcapillary-venular component erythrocyte aggregates and capillarostases.

Experiments on 67 rabbits were performed to examine the injured external cell membranes of the vascular wall, appearing in the blood flow in the course of the development of alimentary hypercholesterolemia. The time of the appearance in the blood plasma of the external cell membranes was judged from the activity of their specific marker, 5'-nucleotidase. An abrupt increase in 5'-nucleotidase activity was disclosed in the blood plasma at the height of hypercholesterolemia. The latter circumstance served as an objective criterion for injury to ther external cell membranes and might be regarded as a risk factor in thrombus formation.

The morphometric, cytophotometric and biochemical methods were used to study the reversibility of changes in the adrenal cortex of rabbits given cholesterol for 14 days. The majority of changes that develop in experimental hypercholesterolemia were discovered to undergo regression 1.5 months after cholesterol withdrawal.

Light and electron microscopy were used in rabbits to study the effect of hypercholesterolemia (HC) on the microcirculatory bed (MCB), perivascular connective tissue and specialized cells of the myocardium. Within the first hours (1, 3, 6, 15, 24, 48 h) after cholesterol single administration to the animals, there were structural changes in the MCB, aggregation and superficial changes in red blood cells (echinocytes), stases, the presence of unusual ultrastructures in elastic membranes (EM) of the arterioles, in the amorphous substance of perivascular connective tissue, specifically near the venules, and focal dystrophy in cardiomyocytes. The ultrastructures detected in the EM of the arterioles and perivascular tissue seem likely to be the complexes of atherogenous lipoproteins and glycosaminoglycans. The transfer of the animals on the atherogenous diet entailed the reconstruction of small arteries of the myocardium and formation in them of so-called "Conti's pillows" as well as lipid deposition. A complex of structural changes revealed in the myocardium in the early stages of HC indicates the increased permeability of the microvessels, alterations in the blood rheological properties and circulatory disorders. A relationship was found between the intensity of the changes cited and blood cholesterol level. Injury to the MCB of an organ is likely to play an initial part in the mechanisms of atherogenesis.

Two-week cholesterol injections caused prolonged alterations of nuclear hepatocyte apparatus in all liver segments. These alterations resulted in the increased number of binuclear cells and hepatocytes containing large nuclei detected 1.5 month after the last cholesterol injection.