MORPHOLOGICAL CHANGES IN SKELETAL MUSCLES OF THE HIND LIMBS OF RATS IN ACUTE ISCHEMIA-REPERFUSION CAUSED BY ARTERIAL TOURNIQUET APPLICATION, AND ITS CORRECTION BY CARBACETAM

Abstract

Summary. Arterial tourniquets are widely used both in clinical practice (for example for angio- and arthroplasty) and in military medicine by the injury of the limbs. 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 search for effective means for drug correction of these disorders still continues.

The aim of the study – to conduct a comparative analysis of structural changes in the skeletal muscles of the hind limbs of rats in acute ischemia-reperfusion caused by the application of an arterial tourniquet, using the correction of disorders with carbacetam.

Materials and Methods. 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 examination was carried out according to standard methods. Sections of the arteries were stained with hematoxylin and eosin, with resorcinol-fuchsin according to Weigart, according to method of Van Gizon and with azan according to the method of Heidenhain, and were examined with a light microscope.

Results. Studies have shown that in the early reperfusion period morphological criteria for skeletal muscle remodeling expressed by swelling of muscle fibers and endo- and perimysium, disorders in the hemomicrocirculatory bed in the form of stasis, hyperemia and microthrombosis, diapedetic hemorrhages, significant leukocyte infiltration, deformation of muscle fibers and the disappearance of their striation, damage to the sarcolemma with the release of nuclei in endomysium, defibering of myofibrils, ruptures and fragmentation of fibers, violation of the linear arrangement of nuclei in them, the appearance of areas of myocytolysis. Subject to the correction of reperfusion disorders by cabacetam, there is a decrease in the degree of damage and more quick restoration of structure of the skeletal muscles, which is the most pronounced in groups of animals with reperfusion terms after 1 and 7 days. Complex of features indicates, that at the tissue level the administration of carbacetam not only reduces the ischemic-reperfusion lesion of the myosymplast, but also accelerates the mechanisms of reparative rhabdomyohistogenesis.

Conclusions. 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 is reduced and the recovery of the skeletal muscle structure of the limb is accelerated.