This article describes protective role of the combined injection of the «Gordox» (Hungary) 10000 ATU/kg and «Cerebrolysin» (Austria) 0,7 ml/kg in a pathogenetic therapy of nervous system damage during reperfusion syndrome. It is determined that preventive usage of that kind combination before revascularization of the ischemic tissues leads to proteolysis activation prevention in a brain, prevents structural violations and leads to main functions of the nervous system saving.

The aim of this study was to determine the general patterns of pathogenetic changes in the blood coagulation system and in non-specific proteinases and their inhibitors during the development of experimental ischemiareperfusion injury. Materials and methods. The study was conducted on 48 male Wistar rats (180–200 g). We used a model of ischemia-reperfusion injury achieved by applying rubber tourniquets to both hind limbs at the inguinal fold level for 6 hours. Revascularization was performed for 6, 12, or 24 hours following the application of tourniquets, after which we examined the state of the internal and external blood coagulation pathways and the activity of nonspecific proteinases and their inhibitors. Results. Indicators of blood coagulation system change show the development of blood hypocoagulation changes as the reperfusion time increases. By the 6th hour of reperfusion, the prothrombin time (PT) was lengthened by 112.0% ( p = 0.0142) and the activated partial thromboplastin time (APTT) by 170.0% ( p = 0.0147) compared with values in the control group. By the 12th reperfusion hour, the PT was lengthened by 174.2% ( p = 0.0389), and the APTT increased 4.9-fold ( p = 0.0002). When the reperfusion period was increased to 24 hours, it was characterized by lengthened PT and APTT, accompanied by an increase in antithrombin III by 11.5% ( p = 0.0371) and a decrease in protein C by 71.4% ( p = 0.0071). Changes in the non-specific proteinases and their inhibitors were characterized by a 2.8-fold increase in the trypsin-like proteinase activity ( p < 0.001) relative to the control, as well as a 2.2-fold decrease in antitrypsin activity and acid-stable inhibitors ( p < 0.001), which reached a maximum after 24 hours of reperfusion. A direct correlation was found between indicators characterizing the deficiency of coagulation system factors and a decrease in antiproteinase potential. Conclusion. Hemostatic system disorders are characterized by the development of hypocoagulation during ischemia-reperfusion injury as the result of an increase in the trypsin-like proteinase activity and a decrease in the levels of inhibitors. The established changes may be associated with the deficiency of coagulation factors and proteinase inhibitors and share common pathogenic mechanisms.

Analysis of pathomorphological changes which taking place in muscle tissue after reperfusion of previouslyischemic rats limbs allowed to identify three phases of the experimental reperfusion syndrome (RS): thefirst or ischemic, the second or initial reperfusional, the third or late reperfusional. Morphological changes ofthe skeletal muscles in the first stage are characterized by presence of dystrophic-necrotic processes and reflectthe compensatory-adaptive reaction of the organism to hypoxia. In the third stage one can see the progress ofmorphological damages, which develop during the ischemic period against a background of exhaustion ofproteinase inhibitors. This indicates the intensity of endogenous intoxication of the organism with the productsof disturbed metabolism and determines the irreversibility of destructive processes and probability of multipleorgan failure. Proceeding from the character of the pathomorphological changes and the state of proteinase-inhibitor system one can suppose, that the optimal time for medical measures is the first stage and the first hours of the second stage (to increase the ischemic tolerance of the skeletal muscles). Taking into account the direct relation between the intensity of pathomorphological injuries and the imbalance of proteinase-inhibitor system, the usage of proteinase-inhibiting medicines for correction of RS-development and reduction of the destructive changes during first and second stages is substantiated. When reperfusion syndrome lasts for a long time, medical measures become ineffective due to the high degree of pathological changes.

Ischemia-reperfusion injury is a significant problem; there is a need for interpretation of its pathogenetic mechanism and a search for potential methods of correction. The aim of this study was to investigate the cytokine content and the proapoptotic protein expression, including caspase-3, in experimental ischemia–reperfusion injury, and to assess the effectiveness of peroxiredoxin 6 treatment. Studies were conducted on 56 white male Wistar line rats weighing 180–200 g, in which ischemia–reperfusion injury was simulated by cross clamping both hind limbs. Proinflammatory cytokines in blood serum, the expression of caspase-3 in the cells of blood vessels, lungs, and kidneys were analyzed after ischemia–reperfusion injury and upon the peroxiredoxin 6 preventive treatment. It was found that the progression of ischemia–reperfusion injury is followed by proinflammatory cytokine activation in the rat blood: the maximum values of interleukin 1β, which were almost 10 times higher than the control, have been observed by 12 h of reperfusion. Ischemia–reperfusion injury was accompanied by an caspase-3 increase in the cells of rat limb vessels and the lungs after 6 h of reperfusion. Peroxiredoxin 6 treatment neutralizes oxidative stress primarily in the limb blood vessels, reducing the degree of vessel tissue destruction in the hind limbs that should be considered as a target for therapy of ischemia–reperfusion injury.

The results of a combined study of the proteolysis on a model of post-ischemic toxemia in rats showed a decrease in antiproteinase potential and an activation of proteolysis. The activation of proteolysis and inhibition of antiproteinases was observed not only in the blood, but also in the bronchoalveolar secretion. Those changes were accompanied with the changes in the morphological structure of the lungs. The data obtained have shown a high effectiveness of proteinase inhibitor (contrical) and an antioxidant of flavonoid group (corvetine). Those drugs decreased the morphological changes in the lungs and prevented the development of imbalance in proteinase-inhibitor system. The prophylactic effect was more considerable when both drugs were used in a combined way.

The morphofunctional state of the small intestine was studied on a tourniquet shock model. The development of postischemic toxemia is followed by disorders of microcirculation leading to irreversible changes in the small intestine. The processes are associated with an increase of the proteolytic activity of the intestinal contents. An oral administration of andecaline prevents ischemia of the intestine, contributes to the preservation of its mucosa.

It was shown that alpha 2-macroglobulin (50 mg/kg, 30 min before revascularization of previously ischemized extremities) significantly inhibits the blood serum proteolytic activity and exerts similarly to contrykal (10,000 U/kg) the correcting effect on the level of arterial blood pressure and parameters of the blood flow in the kidneys, intestine and previously ischemized extremities.

It was shown in Wistar male rats that the development of tourniquet shock was followed by an increase of proteolytic activity in the blood by 3 times, activity of aspartate aminotransferase (AST) by 3 times, that of alanine aminotransferase (ALT) by 6 times, contents of urea and residual nitrogen by 2.5-3 times; level of alpha 1-protease inhibitor (alpha 1-PI) decreased by 4 times and that of alpha 2-macroglobulin (alpha 2MG) by 2.5 times. At administration of contrykal (10,000 U/kg) proteolytic activity increased only by 32.5%, content of alpha 1-PI decreased only by 10-20% and level of alpha 2-MG did not differ from that in healthy animals. Activity of AST and ALT remained high, and contents of urea and residual nitrogen were near-normal.

It was shown on Wistar rats that trypsin and kallikrein decrease the activity of lactate dehydrogenase, alpha-glycerophosphate dehydrogenase, glycogen content and increase the activity of succinate dehydrogenase in neutrophils.