Abstract

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.

Highlights

  • Ischemic-reperfusion lesion is a complex multifactorial process of damage and dysfunction of primary ischemic tissues as a result of restoration of arterial blood circulation in conditions of acute or chronic ischemia [9, 11, 13, 15, 19, 22]

  • 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

  • Literature data indicate that the morphological manifestations of the syndrome of ischemia and reperfusion are impaired hemomicrocirculation, which is histologically manifested by endothelial edema, leukocyte-endothelial adhesion, hemodynamic disorders, reduction of microvascular and arteriovenous shunting, morphofunctional changes in arteries of large diameter, their dynamics, as well as the search for means of tissue protection remains open for further research [9, 13]

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Summary

Introduction

Ischemic-reperfusion lesion is a complex multifactorial process of damage and dysfunction of primary ischemic tissues as a result of restoration of arterial blood circulation in conditions of acute or chronic ischemia [9, 11, 13, 15, 19, 22]. Literature data indicate that the morphological manifestations of the syndrome of ischemia and reperfusion are impaired hemomicrocirculation, which is histologically manifested by endothelial edema, leukocyte-endothelial adhesion, hemodynamic disorders, reduction of microvascular and arteriovenous shunting, morphofunctional changes in arteries of large diameter, their dynamics, as well as the search for means of tissue protection remains open for further research [9, 13]. In reviewing the scientific and experimental literature, we did not find any publications on the use of this drug for the treatment and prevention of complications of ischemia-reperfusion, which prompted an attempt to use carbacetam to study the local correction of reperfusion. The aim of the study was to establish the manifestations of morphofunctional reorganization of the vascular bed of the hind limbs of rats during ischemia-reperfusion and under conditions of correction with carbacetam

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