Comparative analysis of histological and morphometric changes of the arterial bed of the hind limbs of the rats in acute ischemia-reperfusion and correction with carbacetam

Abstract

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-ischemic period was administered carbacetam once a day (5 mg / kg) for 14 days (group II) was performed. 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 the tourniquet. The animals 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 shin, below the level of the application of the tourniquet was examined by Bresser Trino Researcher 40x – 1000x microscope. The morphometric parameters were calculated using SEO Image Lab software from Sumy Electron Optics.

Research results and their discussion. Analyzing of the obtained results, it was founded that after 1 hour of the repefusion the structural changes became systemic, and after 1 day they were the most significant. Histologically, the elastic membranes were thinned and torned up, the swelling became a total character. In the late reperfusion period, a gradual return of morphological changes to the initial state and the increased in the proliferative activity of the fibroblasts were revealed. Under the conditions of correction after 1 day, the positive dynamics became more pronounced and reached its maximum after 7 days of the study. Morphometrically, the differences between the groups are especially pronounced 7 days after the removal of the tourniquet. At the level of the femoral artery revealed a lower value of external (D₁) by 1.9% (p<0,005) and internal (D₂) diameters by 3,0% (p<0,005) and an increased in Vi by 3,54% (p<0,005)) in the specified experimental period in the animals with the correction, compared with the group without it.

In small-caliber arteries, on the contrary, there was a less pronounced vasoconstriction level, when applying the correction, because the value of T decreased by 5,4% (p<0,005) and Vi by 20,28% (p<0,005), but there were higher indicator of D₁ by 1,89 % (p<0,005) and D₂ by 11.55% (p<0,005) compared to the group of animals without the correction.

Conclusions. Ischemia and repfusion cause vascular remodeling after 1 hour with a peak of manifestations after 1 day of reperfusion. Under the conditions of the 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. Morphometric data indicate less pronounced vasodilation at the level of large caliber arteries and spasm of arteries of muscular branches during that experimental period in the group with correction.