Reaction of hemostasis system in hypercapnic hypoxia after the course of mexidol assessed by the method of thromboelastography

Abstract

Aim. To study the reaction of hemostasis system to a single effect of hypercapnic hypoxia of maximum intensity in rats and possibility of correcting hemostasis disorders by means of a preliminary course of an antihypoxant - mexidol.

Methods. The study involved sexually mature male rats (48 specimens) of the Wistar line with an average mass of 274.0 ± 32.0 g. The rats were kept on a standard diet, food and water were fed once a day between 10 and 11 hours. In the evening, animals underwent a single hypercapnic hypoxia in a special flow chamber. The state of hypercapnic hypoxia of maximum intensity was modeled at O2 content of 5.0 %, CO2 - 5.0 % during a single 20-minute exposure. As a training regimen, a 30-fold course of mexidol was used, the drug was administered intraperitoneally to rats at a dose of 50 mg/kg for 1.5 hours prior to exposure to hypercapnic hypoxia.

Results. After a single exposure to hypercapnic hypoxia of maximum intensity, shortening of the onset of clot formation, an increase of alpha angle, and maximum clot density were recorded. Also, the clot formation time shortened and the maximum clot lysis index increased. With a single exposure to hypercapnic hypoxia of maximum intensity after the course of mexidol, a decrease in the maximum clot density was recorded.

Conclusion. A single exposure to hypercapnic hypoxia of maximum intensity was characterized by a shift of hemostatic potential toward hypercoagulability along with fibrinolytic system activation. The course use of antihypoxant mexidol, preceding hypercapnic hypoxia of maximum intensity, significantly reduces the risk of clot formation.

Keywords

hypercapnic hypoxia / hemostasis / thromboelastography / mexidol

References

[1] Novikov V.E., Katunina N.P. Pharmacology and biochemistry of hypoxia. Obzor po klinicheskoy farmakologii i ­lekarstvennoy terapii. 2002; 1 (2): 73–78. (In Russ.)

[2] Новиков В.Е., Катунина Н.П. Фармакология и биохимия гипоксии. Обзор по клинической фармакологии и лекарственной терапии. 2002; 1 (2): 73-78.

[3] Agadzhanyan N.A., Stepanov O.G., Arkhipenko Yu.V. Adaptation to hypoxia as a method of treatment and prevention of mucosal damage of stomach and duodenum. Byulletenʹ ehksperimentalʹnoy biologii i meditsiny. 2001; 132 (9): 358–360. (In Russ.)

[4] Агаджанян Н.А., Степанов О.Г., Архипенко Ю.В. Адаптация к гипоксии как метод лечения и профилактики поражений слизистой оболочки желудка и двенадцатиперстной кишки. Бюллетень экспериментальной биологии и медицины. 2001; 132 (9): 358-360.

[5] Shakhmatov I.I., Vdovin V.M., Kiselev V.I. State of hemostasis in different types of hypoxic effect. Byulletenʹ SO RAMN. 2010; 2: 131–138. (In Russ.)

[6] Шахматов И.И., Вдовин В.М., Киселев В.И. Состояние системы гемостаза при различных видах гипоксического воздействия. Бюллетень СО РАМН. 2010; 2: 131-138.

[7] Grinevich I.V. Effect of adaptation to hypoxic hypoxia on cellular composition of the spleen. Patologiya. 2011; 8 (2): 127–129. (In Russ.)

[8] Гриневич И.В. Влияние адаптации к гипоксической гипоксии на клеточный состав селезенки. Патология. 2011; 8 (2): 127-129.

[9] Пак Г.Д. Влияние дыхательной гипоксии на свер-

[10] Пак Г.Д. Влияние дыхательной гипоксии на свертывающую систему крови у собак. Вестник АН КазСССР. 1979; 10: 50-52.

[11] Pak G.D. Effect of respiratory hypoxia on coagulation system in dogs. Vestnik AN KazSSSR. 1979; 10: 50–52. (In Russ.)

[12] Mannucci P.M., Gringeri A., Peyvandi F., Paolantonio T. Di, Mariani G. Short-term exposure to high altitude causes coagulation activation and inhibits fibrinolysis. Thrombosis and Haemostasis. 2002; 87 (2): 342-343. DOI: 10.1055/s-0037-1612997.

[13] Mannucci P.M., Gringeri A., Peyvandi F., Paolantonio T. Di, Mariani G. Short-term exposure to high altitude causes coagulation activation and inhibits fibrinolysis. Thrombosis and Haemostasis. 2002; 87 (2): 342–343. DOI: 10.1055/s-0037-1612997.

[14] Куликов В.П., Полухина М.Г., Беспалов А.Г. и др. Влияние гипоксически-гиперкапнического прекондиционирования на гемостаз, реологию и толерантность головного мозга к ишемии. Региональное кровообращение и микроциркуляция. 2004; 3 (1): 27-32.

[15] Kulikov V.P., Polukhina M.G., Bespalov A.G., et al. Effect of hypoxic-hypercapnic preconditioning on hemostasis, reology and tolerance of brain to ischemia. Regionalʹnoe krovoobrashchenie i mikrotsirkulyatsiya. 2004; 3 (1): 27–32. (In Russ.)

[16] Toff W.D., Jones C.I., Ford I., Pearse R.J., Watson H.G., Watt S.J., et al. Effect of hypobaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function, and endothelial activation. JAMA. 2006; 295: 2251-2261. DOI: 10.1001/jama.295.19.2251.

[17] Toff W.D., Jones C.I., Ford I., Pearse R.J., Watson H.G., Watt S.J., et al. Effect of hypobaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function, and endothelial activation. JAMA. 2006; 295: 2251–2261. DOI: 10.1001/jama.295.19.2251.

[18] West J.B., Schoene R.B., Milledge J.S. High Altitude Medicine and Physiology. USA: Hodder Arnold. 2007; 499 p.

[19] West J.B., Schoene R.B., Milledge J.S. High Altitude Medicine and Physiology. USA: Hodder Arnold. 2007; 499 p.

[20] Стратиенко Е.Н., Петухова Н.Ф. Поиск средств фармакологической коррекции гипоксических состояний. Вестник Брянского государственного университета. 2012; 4 (2): 232-234.

[21] Stratienko E.N., Petukhova N.F. Search for ways of pharmacological correction of hypoxia. Vestnik Bryanskogo gosudarstvennogo universiteta. 2012; 4 (2): 232–234. (In Russ.)

[22] Александров О.В., Стручков П.В., Виницкая Р.С. и др. Клинико-функциональный эффект курса интервальной нормобарической гипокситерапии у больных хроническим обструктивным бронхитом и бронхиальной астмой. Терапевтический архив. 1999; 3: 28-32.

[23] Aleksandrov O.V., Struchkov P.V., Vinitskaya R.S., et al. Clinical functional effect of interval normobaric hypoxic therapy for patients with chronic obstructive bronchitis and bronchial asthma. Terapevticheskiy arkhiv. 1999; 3: 28–32. (In Russ.)

[24] Левченкова О.С., Новиков В.Е. Индукторы регуляторного фактора адаптации к гипоксии. Российский медико-биологический вестник им. акад. И.П. Павлова. 2014; 2: 134-143.

[25] Levchenkova O.S., Novikov V.E. Inductors of regulatory factor of adaptation to hypoxia. Rossiyskiy mediko-biologicheskiy vestnik imeni akademika I.P. Pavlova. 2014; 2: 134–143. (In Russ.)

[26] Каркищенко Н.Н. Фармакология процессов адаптации и переносимости предельных нагрузок в спорте и режимах работы «до отказа»: второй тайм для дженериков. Биомедицина. 2010; 4: 6-23.

[27] Karki­shchenko N.N. Pharmacology of adaptation processes and endurances of maximum loads in sports and operating mode “to overflowing“: the second time for generics. Biomeditsina. 2010; 4: 6–23. (In Russ.)

[28] Чукаев С.А. Оценка фармакотерапевтической эффективности мексидола в качестве средства коррекции гипоксических ишемических и реоксигенационных повреждений. Вестник Бурятского государственного университета. 2014; 12: 19-24.

[29] Chukaev S.A. Evaluation of mecsidol pharmacotherapeutical efficiency as a remedy of correction at hypoxia, ischemia and reoxigination injury. Vestnik Buryatskogo gosudarstvennogo universiteta. 2014; 12: 19–24. (In Russ.)

[30] Микуляк Н.И., Иванов П.В, Захаркин А.Г. Экспериментальное исследование эффективности препарата с антиоксидантным типом действия - мексидола на гемостаз при лучевой терапии. Кубанский научный медицинский вестник. 2009; 1: 72-76.

[31] Mikulyak N.I., Ivanov P.V, Zakharkin A.G. Experimental studies of antioxidant mexidole medicine on hemostasis in x-ray therapy. Kubanskiy nauchnyy meditsinskiy vestnik. 2009; 1: 72–76. (In Russ.)

[32] Москаленко С.В., Шахматов И.И., Бондарчук Ю.А. и др. Влияние однократного и многократного воздействия гипоксической гипоксии сильной интенсивности на состояние системы гемостаза у крыс. Сибирский научный медицинский журнал. 2018; 1: 32-37. DOI: 10.15372/SSMJ20180105.

[33] Moskalenko S.V., Shakhmatov I.I., Bondarchuk Yu.A., et al. Effect of single and multiple impact of hypoxic hypoxia of strong intensity on the state of the hemostatic system in rats. Sibirskiy nauchnyy meditsinskiy zhurnal. 2018; 1: ­32–37. (In Russ.)

[34] European Convention for the Protection of vertebrate animals used for experimental and other scientific purposes. Strasburg: Council of Europe. 1986; 51 p.

[35] European Convention for the Protection of vertebrate animals used for experimental and other scientific purposes. Strasburg: Council of Europe. 1986; 51 p.

[36] Москаленко С.В. Система гемостаза у крыс при изолированном и сочетанном воздействии мексидола и гипоксической гипоксии с использованием метода тромбоэластографии. Фундаментальные и прикладные исследования: проблемы и результаты. 2016; 27: 34-43.

[37] Moskalenko S.V. Hemostasis in rats in isolated and combined effect of mexidol and hypoxic hypoxia with the use of thromboelastography. Fundamentalʹnye i prikladnye issledovaniya: problemy i rezulʹtaty. 2016; 27: 34–43. (In Russ.)

[38] Checchin D., Sennlaub F., Sirinyan M., Brault S., Zhu T., Kermorvant-Duchemin E., et al. Hypercapnia prevents neovascularization via nitrative stress. Free Radical Biology and Medicine. 2006; 40: 543-553. DOI: 10.1016/j.freeradbiomed.2005.09.016.

[39] Checchin D., Sennlaub F., Sirinyan M., Brault S., Zhu T., Kermorvant-Duchemin E., et al. Hypercapnia prevents neovascularization via nitrative stress. Free Radical Biology and Medicine. 2006; 40: 543–553. DOI: 10.1016/j.freeradbiomed.2005.09.016.

[40] Kimura C., Koyama T., Oike M., Ito Y. Hypotonic stress-induced NO production in endothelium depends on endogenous ATP. Biochem. Biophys. Res. Commun. 2000; 3: 736-740. DOI: 10.1006/bbrc.2000.3205.

[41] Kimura C., Koyama T., Oike M., Ito Y. Hypotonic stress-induced NO production in endothelium depends on endogenous ATP. Biochem. Biophys. Res. Commun. 2000; 3: 736–740. DOI: 10.1006/bbrc.2000.3205.

RIGHTS & PERMISSIONS

Moskalenko S.V., Shakhmatov I.I., Bondarchuk Y.A., Alekseeva O.V., Ulitina O.M.