Annotation. The ischemic-reperfusion lesion, which occurs during the restoration of the arterial circulation, causes structural and spatial reorganization of the arterial bed of the hind limbs of the rats. Recently, more and more attention has been paid to the treatment and prevention of the ischemic changes are given to the nootopic medicines, among which carbacetam stands out. The aim of the study – to establish the manifestations of the structural-spatial remodeling of the arterial bed of the hind limbs of the rats in the femoral, popliteal and tibial anatomical areas during ischemia-reperfusion and under conditions of the correction with carbacetam. An X-ray examination was performed of the arterial bed of the hind limbs of 30 rats under conditions of the ischemia-reperfusion (group I) and 30 rats in the simulation of the ischemia-reperfusion, which were injected carbacetam once a day (5 mg/kg) during 14 days in postischemic period. There were 6 intact animals in the control group. Simulation of the ischemia was performed by applying SWAT rubber tourniquets on the hind limbs for 2 hours, and reperfusion by removal of the arterial tourniquet. The animals of the experimental groups were divided into 5 subgroups with reperfusion terms after 1, 2 hours and 1 day, as well as after 7 and 14 days. The filling of the arterial bed with a suspension of lead sulfide and the radiography were performed. Research morphometric parameters were calculated using the SEO Image Lab software of Sumy Electron Optics. The diameters of the main column (D0,), thicker (D1,) and thinner (D2,) subsidiary branches were determined, and the asymmetry coefficient (H2) was calculated. Statistical processing of the material was carried out using a program package “Microsoft Exсel”. Research results and their discussion. Visual analysis revealed dilatation of the main vascular columns and reduction of angioarchitectonics of the limb, most likely after 1 day, which was confirmed morphometrically. In particular, in the femoral region by 15.77 % (p<0.005) increased (D0) by 12.77 % (p<0.05) – (D1) and by 20.93 % (p<0.005) – (D2). and the asymmetry coefficient (H2) increased by 9.36 % (p<0.05). In the popliteal area at the end of 1 day there was an increase in the lumen of D0 by 18.49 % (p<0.005) and its subsidiary branches D1 and D2 by 15.8 % (p<0.05) and 25.12 % (p<0.05), respectively. The value of H2 increased in this group by 10.56 % (p<0.005). In the area of the tibia during this period there was an increase in the indicator (D0) by 19.54 % (p<0.05), and indicators D1 and D2 – by 12.58 % (p>0.05) and 23.51 % (p<0.05), respectively, and the asymmetry coefficient (H2) – increased by 11.78 % (p<0.05). After 14 days after the resumption of blood supply, the morphometric parameters of the arterial tees decreased and approached the level of the values of the control group. On the X-ray angiograms of the animals with using a correction, an also have signs of the vascular dilatation, but their intensity was less relative to the group, in which correcting was not performed. Thus, in the area of the femoral artery through 1 day of reperfusion marked on decreasing in D0 by 4.0 % (p<0.005), D1 by 2.0 % (p<0.005), D2 by 3.96 % (p<0.005), and H2 by 2.51 % (p<0.005) in the group with correction compared to similar indicators without correction. On the X-ray angiograms of the animals with using a correction, an also have signs of the vascular dilatation, but their intensity was less relative to the group, in which correcting was not performed. Thus, in the area of the femoral artery through 1 day of reperfusion marked on decreasing in D0 by 4.0 % (p<0.005), D1 by 2.0 % (p<0.005), D2 by 3,96 % (p<0.005), and H2 by 2.51 % (p<0.005) in the group with correction compared to similar indicators of the group without correction. At the levels of the popliteal artery, after the application of the correction, the index D0 was lower by 3.0 % (p<0.005), D1 by 2.02 % (p<0.005), D2 by 4.0 % (p<0.005), and H2 by 2.58 % (p<0.005) compared with a group of the animals without correction. In the tibia using of carbacetam caused a decrease in the values of D0 by 3.0 %, D1 by 3.0 % (p<0.005), D2 and H2 by 4.36 % (p<0.005) and 3.83 % (p<0.005) in accordance. Thus, simulated ischemia-reperfusion supplementation with morfo-functional reorganization of the arteries of the hind limbs of the rats at all studied levels after 1 hour of the reperfusion and reaching the highest values after 1 day. Gradually, returning of the studied indicators to the control group occurs after 14 days of the experiment, and the application of correction helps to return the basic parameters of vascular tees at all levels to the control group after 7 days of the experiment.

The ischemic-reperfusion lesion is a complex multifactorial damage of the primary ischemic tissues as a result of restoration of the arterial blood circulation in them, which is accompanied by local morpho-functional reorganization of the vascular bed of the hind limbs of the rats. One of the promising means in the treatment and prevention of the reperfusion disorders is a carbacetam, which smooths the phenomena of hypo- and hyperperfusion in the post-ischemic period. The aim of the study was to established the manifestations of the morpho-functional remodeling of the vascular bed of the hind limbs of the rats in ischemia-reperfusion and under conditions of correction with carbacetam. Histological examination of the vascular bed of the hind limbs of 30 rats under conditions of ischemia-reperfusion (group I) and 30 rats in the simulation of ischemia-reperfusion, which in the post-ischemic period administered carbacetam once a day (5 mg/kg) for 14 days (group II) were done. There were 6 intact animals in the control group. Simulation of ischemia was performed by applying SWAT rubber tourniquets on the hind limbs for 2 hours, and reperfusion – by removing of the tourniquet. The animals of the experimental groups were divided into 5 subgroups with reperfusion terms after 1, 2 hours and 1 day, as well as after 7 and 14 days. Histological examination was performed according to generally accepted methods. The vascular bed in the middle third of the thigh and the shin below the tourniquet was examined using a Bresser Trino Researcher 40x–1000x microscope. Analyzing of the obtained results, was established that after 1 hour of the reperfusion the histological changes became a systemic, and after 1 day it were more significant. It should be noted that the thickness of the vessel walls increased, and the elastic membranes were partially eligned, thinned and torned. The stepwise clarity of the arterials walls structure was lost. The edema acquired a total nature. The histological examination of the vessels after 7 days revealed that the swelling of the walls decreased and the condition of the elastic frame was improved. There was a proliferation of collagen fibers in the adventitia, which was a response to ischemic effects. It is noted that after 14 days in all wall membranes the proliferative activity of fiboblasts was remained. Under the conditions of the correction with the carbacetam after 2 hours, the structural positive dynamics became more pronounced and increased to a maximum level after 7 days of the experiment. The number of the modified and exfoliated endothelial cells decreased, and the condition of smooth myocytes increased. Histologically, the gradual restoration of endothelial coverage of the intima was established. As follows, ischemia and reperfusion cause vascular remodeling after 1 hour with a peak of the manifestations after 1 day of the reperfusion, which includes edematous syndrome, dystrophic-degenerative changes with an inflammatory response to the damage, and in the late reperfusion period increased a fibroblasts activity. Gradual return of morphological changes occurs after 14 days of the experiment. Under the conditions of correction, the acceleration of the remodeling with stabilization of the process and the most possible structural restoration after 7 days of the study was noted.

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Resume. Ischemic-repefusion injury is a complex multifactorial tissue damage as the result of restoration of blood circulation, after the period of ischemia or lack of the oxygen, accompanied by the local and systemic disorders. Recently, more and more attention in treatment and prevention of postischemic disorders is paid to nootropic medicine, which smooths the phenomena of hypo-and hyperperfusion, and also improves tissue microcirculation.The aim of the study was to establish the manifestations of morpho-functional remodeling of the vascular bed of the hind limbs of the rats during ischemia-reperfusion and under conditions of carbacetam correction using histological and morphometric іnvestigations methods. Materials and methods.There was histological and morphometric examination of the arterial bed of the hind limbs of 30 rats under conditions of ischemia-reperfusion injury (group I) and 30 rats in the simulation of ischemia-reperfusion injury, which in the post-

Arterial tourniquets are used in clinical practice for angioplasty and arthroplasty, and in case of limb injuries, their use often occurs according to vital signs. After removing the tourniquet and blood supply restoration to the limb arises a multifactorial lesion of tissues both ischemic and distant from the site of ischemia. A number of publications have been devoted to the study of morphological disorders in muscle tissue in acute ischemia-reperfusion in the medical literature. However, the researches for effective means for drug correction of these disorders still continues. The aim of the study was to explore peculiarities of skeletal muscle remodeling of the hind limbs of rats, detected by polarization microscopy, in acute ischemia-reperfusion, caused by the application of an arterial tourniquet, and in the correction of reperfusion disorders by carbacetam. Microscopic examination of histological sections of skeletal muscles of the hind limbs of 60 rats below the site of application of the tourniquet under conditions of experimental acute ischemia-reperfusion was performed. Acute ischemia for all animals was caused by application of SWAT rubber bands on the hind limbs of animals, 5–6 mm in width, at the inguinal fold level within 2 hours under thiopental anesthesia. A reperfusion was modeled by removing the tourniquet. Half of the experimental animals in the reperfusion period for the purpose of correction intraperitoneally was administered the nootropic drug 1-oxo-3.3.6-trimethyl-1.2.3.4-tetrahydroindolo[2.3-c]quinoline (carbacetam) at a dose of 5 mg per kilogram of body weight once a day during the entire reperfusion period. The histological specimens of the skeletal muscles were stained with hematoxylin and eosin, and were examined with a light microscope with polarization nozzle. Studies with using the polarization microscopy have shown that in the early reperfusion period morphological criteria for skeletal muscle remodeling expressed by deformation and anisotropy of muscle fibers, disappearance of their transverse striation, cracks and ruptures of fibers, and in the most severe cases there were signs of necrosis of the fibers with their fragmentation into separate lumps. Subject to the correction of reperfusion disorders by carbacetam, there is a decrease in the degree of damage and consistent acceleration of restoration of the skeletal muscles structure, which was the most pronounced in groups of animals with reperfusion terms after 1 and 14 days. Complex of features indicates, that at the tissue level the administration of carbacetam as reduces the ischemic-reperfusion lesion of the muscular fibers, as also accelerates the mechanisms of reparative rhabdomyohistogenesis. Thus, structural changes in the skeletal muscles of the limb after two-hour ischemia and subsequent reperfusion increased in the early reperfusion period and reached its peak after 1 day of reperfusion, and in the late period of reperfusion their reverse development took place. With the correction of disorders by carbacetam, the degree of damage was reduced and the recovery of the skeletal muscle structure of the limb was accelerated.