PATHOMORPHOLOGICAL CHANGES OF THE SKELETAL MUSCLES UNDER FORMATION OF THE REPERFUSION SYNDROME.

Analysis of pathomorphological changes which taking place in muscle tissue after reperfusion of previously ischemic rats limbs allowed to identify three phases of the experimental reperfusion syndrome (RS): the first or ischemic, the second or initial reperfusional, the third or late reperfusional. Morphological changes of the skeletal muscles in the first stage are characterized by presence of dystrophic-necrotic processes and reflect the compensatory-adaptive reaction of the organism to hypoxia. In the third stage one can see the progress of morphological damages, which develop during the ischemic period against a background of exhaustion of proteinase inhibitors. This indicates the intensity of endogenous intoxication of the organism with the products of disturbed metabolism and determines the irreversibility of destructive processes and probability of multiple organ 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.

[Experimental approach to the prophylaxis and treatment of acute lung injury syndrome with proteinase inhibitors and corvitin]. / Eksperymental'ni pidkhody do profilaktyky ta likuvannia syndromu hostroho ushkodzhennia lehen' z vykorystanniam inhibitoriv proteïnaz i korvitynu.

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.

[Pancreatic kallikrein, a protector of small intestine damage in post-ischemic toxemia]. / Pankreaticheskii kallikrein--protektor povrezhdeniia tonkogo kishechnika pri postishemicheskoi toksemii.

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.

[Effect of alpha 2-macroglobulin on indices of the proteolysis system and organ blood flow in tourniquet shock]. / Vliianie al'fa 2-makroglobulina na pokazateli sistemy proteoliza i organnogo krovotoka pri turniketnom shoke.

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.

[Effect of kontrikal on the dynamics of proteolytic system indices in postischemic toxemia]. / Vliianie kontrikala na dinamiku pokazatelei sistemy proteoliza pri postishemicheskoi toksemii.

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.

[Effect of trypsin, kallikrein and kontrikal on the enzyme activity and cationic protein content of the blood neutrophils]. / Vliianie tripsina, kallikreina i kontrikala na aktivnost' nekotorykh fermentov i soderzhanie kationnykh belkov v neitrofilakh krovi.

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.

[Effect of kontrikal on the activity of proteolytic enzymes and their inhibitors in blood, state of the bronchoalveolar secretion and the nature of the lung damage in dysenteric intoxication]. / Vliianie kontrikala na aktivnost' fermentov proteoliza i ikh ingibitorov v krovi, sostoianie bronkhoal'veoliarnogo sekreta i kharakter porazheniia legkikh v usloviiakh dizenteriinoi intoksikatsii.

The development of dysenteric intoxication in rabbits led to an abrupt increase in the blood activity of proteolytic enzymes. This increase was accompanied by the reduced content of alpha 1-antitrypsin, and that of rapid and slow kallikrein inhibitor. Meanwhile there occurred a remarkable decrease in blood serum ability to bind chymotrypsin and kallikrein, and diminution of alpha 2-macroglobulin level. Trypsin, binding by blood serum did not undergo any substantial changes. In these conditions, the permeability of pulmonary vessels drastically rose and surface activity of the washing off dropped. The pathomorphological alterations in the lungs corresponded with the appearance of the "shock lung". Contrykal normalized the blood content of proteolytic enzymes and inhibitors, as well as that of the bronchoalveolar washing off, averted the development of gross pathomorphological alterations, exerting no appreciable effect on the surface activity of the bronchoalveolar washing off.

[Effect of proteolysis inhibitors on serum proteinase activity and its antitryptic activity in postischemic toxemia]. / Vliianie ingibitorov proteoliza na aktivnost' proteinaz syvorotki krovi i ee antitripticheskuiu aktivnost' pri postishemicheskom toksemii.

Parenteral administration to animals of the antikallikrein serum containing 200gamma/ml of antibodies to the pancreatic kallikrein (10 ml/kg), ingitryl (1.5 Un/kg) and of tracilol (10 000 Un/kg) exerts in post-ischemic toxemia an inhibiting effect on the protamine-splitting blood serum activity and does not affect the benzoylarginine-paranitroanilide rate of splitting. Changes of the blood serum ability to bind trypsin and manifestation of the protamine-splitting activity during the first 9 hours of observation are of an undulating nature and the changes of these characteristics are reciprocal.

[Effect of pancreatic kallikrein and trypsin inhibitors on the course of postischemic toxemia]. / Vliianie ingibitorov pankreaticheskgo kallikreina i tripsina na techenie postishemicheskoi toksemii.

By studying the ECG findings, dynamic changes of the body temperature, the edemas size in the tourniquet-compressed limbs, vascular permeability of the skin, general condition and survival rate on a model of post-ischemic toxemia in albino rats it was found that the serum containing antibodies to pancreatic kallikrein (200 gamma/ml), when introduced parenterally (1 ml per 100 g of the mass), increases the survival time of the animals and prevents the development of gangrene in the ischemic limbs. The curative effect of the antikallikrein serum resembles the action of ingitril, a polyvalent inhibitor (1.5 Un. per 100 g of the mass). The antitryptic serum employed in analogous doses stands by its action close to the normal rabbit's serum.