Kazan medical journalKazan medical journal0368-48142587-9359Eco-Vector1553210.17816/KMJ2019-642Research ArticleReaction of the hemostatic system in response to hypercapnic hypoxia of maximum intensity depending on different types of preconditioningMoskalenkoS Vsunrisemsv@gmail.comShakhmatovI Isunrisemsv@gmail.comKovalevI Vsunrisemsv@gmail.comShakhmatovaK Isunrisemsv@gmail.comVdovinV Msunrisemsv@gmail.comAltai State Medical UniversityResearch Institute of Physiology and Fundamental MedicineSiberian State Medical UniversityOtdelenchesky clinical hospital at the station Barnaul of JSC “Russian Railways”31072019100464264930072019Copyright © 2019, Moskalenko S.V., Shakhmatov I.I., Kovalev I.V., Shakhmatova K.I., Vdovin V.M.2019<p><strong>Aim.</strong> To study the adaptation reactions of the hemostasis system to hypercapnic hypoxia of maximum intensity in rats subjected to preliminary multiple exposure to ethylmethylhydroxypyridine succinate and hypercapnic hypoxia of submaximal intensity.</p>
<p><strong>Methods.</strong> In the experiment, Wistar male rats (80 individuals) were used. Training cycles: 30-fold daily exposure to hypercapnic hypoxia of submaximal intensity (20 minutes 9.00.5% O2, 7.00.5% CO2); administration of ethylmethylhydroxypyridine succinate (50 mg/kg) to animals for 30 days; combined effects of the two described modes. Tested experimental exposure was simulated as a single hypercapnic hypoxia of maximum intensity (20 minutes 5.00.5% O2, 5.00.5% CO2) at the end of each of three 30-day training cycles.</p>
<p><strong>Results.</strong> Preliminary 30-day exposure to both isolated hypercapnic hypoxia of submaximal intensity and combined exposure to ethylmethylhydroxypyridine succinate contributes to hypocoagulation shift in the hemostasis system and reduces the level of the markers of pre-thrombotic state in response to a single hypercapnic hypoxia of maximum intensity. The state of the hemostasis system after 30-day cycle of isolated use of an antihypoxant is characterized by the inhibition of the vascular-platelet system of the hemostasis system and preserved hypercoagulation shifts in its plasma unit. The obtained results suggest that both preliminary isolated effect of hypercapnic hypoxia of submaximal intensity and the combined effect of hypercapnic hypoxia and ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system in experimental animals to acute hypercapnic hypoxia of maximum intensity compared to rats of the control group. This was confirmed by the inhibition of the vascular-platelet system, hypocoagulation in the plasma unit, decrease in the level of thrombotic readiness markers and increase in the anticoagulant activity of the blood system compared to the control. At the same time, isolated course administration of ethylmethylhydroxypyridine succinate did not cause the same amount of adaptive changes to maximum intensity hypercapnic hypoxia, since only platelet suppression of the hemostasis and hypocoagulation via the internal coagulation pathway were registered.</p>
<p><strong>Conclusion.</strong> Isolated exposure of hypercapnic hypoxia of submaximal intensity and its combined exposure with ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system to acute hypercapnic hypoxia of maximum intensity; isolated course administration of ethylmethylhydroxypyridine succinate does not cause the same amount of adaptive changes.</p>hemostasishypercapnic hypoxiaethylmethylhydroxypyridine succinateгемостазгиперкапническая гипоксияэтилметилгидроксипиридина сукцинат[Malkova Ya.G., Kal’chenko G. The use of various models of hypoxia in experimental pharmacology. Molodoy uchenyy. 2010; (3): 318–319. (In Russ.)][Sukhovershin A.V., Pantin A.V., Sukhovershin R.A. et al. Rehabilitation treatment of patients with neurasthenia with the use of hypercapnic hypoxia in the conditions of a spa resort. Sibirskiy vestnik psikhiatrii i narkologii. 2009; (1): 127–129. (In Russ.)][Danilov A.N., Lobanov Yu.F., Seroshtanova E.V. et al. Clinical observation of the course of bronchial asthma in a preschool child training in hypercapnic hypoxia on a carbonic simulator. Sovremennye problemy nauki i obrazovaniya. 2013; (6): 594–603 (In Russ.)][Pechkina K.G., Kulikov V.P., Shcherbakov P.L., Lobanov Yu.F. Treatment of chronic erosive gastroduodenitis in children using hypercapnic hypoxia. Gastroenterologiya eksperimental'naya i klinicheskaya. 2011; (1): 28–30. (In Russ.)][Senin I.P., Mishustin Yu.N. Hypercapnic training as a means of eliminating tissue hypoxia. Zhurnal of GrSMU. 2006; (1): 81–83. (In Russ.)][Shakhmatov I.I., Vdovin V.M., Kiselev V.I. The state of the hemostasis system in various types of hypoxic exposure. Byulleten’ SORAMN. 2010; (2): 131–138. (In Russ.)][Schobersberger W., Hoffmann G., Gunga H. Interаktionen von Hypoxie und Hämostase — Hypoxie als prothrombotischer Faktor in der Höhe? Wien. Med. Wochenschr. 2005; 155: 157–162. DOI: 10.1007/s10354-005-0163-7.][Kuznik B.I. Kletochnye i molekulyarnye mekhanizmy regulyatsii sistemy gemostaza v norme i patologii. (Cellular and molecular mechanisms of hemostatic system regulation in norm and pathology.) Chita: Ekspress izdatel'stvo. 2010; 832 p. (In Russ).][Novikov V.E., Levchenkova O.S., Pozhilova E.V. Preconditioning as a method of metabolic adaptation of the organism to conditions of hypoxia and ischemia. Vestnik Smolenskoy gosudarstvennoy meditsinskoy akademii. 2018; (1): 69–79. (In Russ.)][Bespalov A.G., Kulikov V.P., Lepilov A.V. Training with hypoxic hypercapnia as a means of increasing brain tolerance to ischemia. Patologiya krovoobrashcheniya i kardiokhirurgiya. 2004; (3): 60–64. (In Russ.)][Kulikov V.P., Bespalov A.G., Yakushev N.N. The effectiveness of hypercapnic hypoxia in increasing the tolerance of the brain to ischemia. Vestnik vosstanovitel'noy meditsiny. 2009; (5): 22–31. (In Russ.)][Moskalenko S.V. The hemostasis system in rats with isolated and combined effects of Mexidol and hypoxic hypoxia using the method of thromboelastography. Fundamental'nye i prikladnye issledovaniya. 2016; (27): 34–43. (In Russ.)][Stratienko E.N., Petukhova N.F. Search for means of pharmacological correction of hypoxic states. Vestnik Bryanskogo gosudarstvennogo universiteta. 2012; 4 (2): 232–234. (In Russ.)][Srubilin D.V., Enikeev D.A., Myshkin V.A. Antiradical and antioxidant activity of the complex compound of 5-hydroxy-6-methyluracil with succinic acid and its efficacy in hypoxic conditions. Fundamental'nye issledovaniya. 2011; (6): 166–170. (In Russ.)][Yasnetsov V.V., Smirnov L.D. The effectiveness of new 3-hydroxypyridine derivatives with antioxidant activity, with various types of hypoxia. Proceedings of the international conference Bioantioxidant. Moscow. 2006; 292–293. (In Russ.)][Council Directive of 24 November 1986 on the Approximation of Laws, Regulations of the Member States Regarding the Protection of Animals Used for Experimental and Other Purposes Directive (86/609/EEC). Official J. Eur. Communities L. 262; 1–29.][Khabriev P.U. Rukovodstvo po eksperimental'nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv. (Manual on experimental (preclinical) study of new pharmacological substances.) Moscow: Meditsina. 2005; 832 р. (In Russ.)][Moskalenko S.V., Shakhmatov I.I., Bondarchuk Yu.A. et al. The reaction of the hemostasis system in hypercapnic hypoxia after the course of the application of Mexidol using the method of thromboelastography. Kazanskiy Meditsinskiy Zhurnal. 2018; 99 (6): 919–924. (In Russ.)][Chukaev S.A. Evaluation of the pharmacotherapeutic efficacy of Mexidol as a means of correcting hypoxic ischemic and reoxygenation damages. Vestnik Buryatskogo gosudarstvennogo universiteta. 2014; (12): 19–24. (In Russ.)][Rachkov A.G., Rachkova L.G., Daniyarov S.B. The effect of acute blood loss on hemostasis in dogs unadapted to the conditions of high mountains. Patologicheskaya fiziologiya i eksperimental'naya terapiya. 1990; (5): 28–30. (In Russ.)][Shevchenko Yu.L. Gipoksiya. Adaptatsiya, patogenez, klinika. (Hypoxia. Adaptation, pathogenesis, clinic.) Saint. Petersburg: Elbi-SPb. 2000; 384 р. (In Russ.)][Shakhmatov I.I., Nosova M.N., Bondarchuk Yu.A. Anticoagulant properties of Eleutherococcus. Khimiya rastitel'nogo syr'ya. 2011; (3): 179–182. (In Russ.)][Chereshnev V.A., Yushkov B.G., Klimin V.G., Lebedeva E.V. Immunofiziologiya. (Immunophysiology.) Ekaterinburg: UrORAN. 2002; 260 р. (In Russ.)][Zhang Z.G., Chopp M., Goussev A. et al. Cerebral microvascular obstruction by fibrin is associated with upregulation of PAI-1 acutely after onset of focal embolic ischemia in rats. J. Neurosci. 1999; 19 (24): 10 898–10 907. DOI: 10.1523/JNEUROSCI.19-24-10898.1999.]