The role of physical exercise in modulating hemostatic parameters under hypobaric hypoxia

Abstract

BACKGROUND: Exposure to multiple extreme environmental factors disrupts the function of multiple organ systems, including the hemostatic system. Identifying safe and effective strategies to enhance the body’s adaptive capacity can help mitigate or prevent stress-related consequences.

AIM: This study aimed to assess the response of the hemostatic system to a single 24-h exposure to hypobaric hypoxia and evaluate the potential of preconditioning with physical exercise to correct associated abnormalities.

MATERIAL AND METHODS: The experiment involved 60 sexually mature male rats. Group 1 (n = 24) served as the control. Rats in group 2 (n = 12) underwent daily 2-h treadmill walking at a speed of 6–8 m/s for 30 days. Those in group 3 (n = 12) were exposed to a single 24-h hypobaric hypoxia episode by placing the rats in a hypobaric chamber at 0.55 kgf/cm², simulating an altitude of 6,500 m above sea level. Group 4 rats (n = 12) received a 2-h daily exercise regimen for 30 days prior to a 24-h exposure to hypobaric hypoxia. Platelet aggregation activity, plasma coagulation, and the activity of anticoagulant and fibrinolytic systems were evaluated in all groups using diagnostic test kits (Technologia-Standart, Russia). Statistical analysis was performed using the software Statistica 10. Data were tested for statistical significance of differences using the Student t test and the nonparametric Mann–Whitney U test.

RESULTS: A 24-h hypobaric hypoxia activated both the platelet and plasma arms of hemostasis, as shown by significantly shortened platelet aggregation time (p = 0.000), silica clotting time (p = 0.006), and prothrombin time (p = 0.008). Additionally, antithrombin III levels significantly declined (p = 0.000) and fibrin-lysis time lengthened (p = 0.001) relative to those of the controls. Preconditioning physical training followed by hypoxic exposure resulted in hypocoagulation, manifested as a significant prolongation of platelet aggregation time (p = 0.000), silica clotting time (p = 0.011), kaolin clotting time (p = 0.000), and prothrombin time (p = 0.000). Furthermore, antithrombin III concentration significantly increased (p = 0.000) and fibrin clot lysis time significantly decreased (p = 0.002) relative to those of the untrained animals exposed to hypoxia alone.

CONCLUSION: A single episode of hypoxic stress is characterized by hypercoagulation at all stages of the coagulation cascade, accompanied with suppression of plasma anticoagulant and fibrinolytic activity, which is mitigated by prior physical training.

Keywords

hemostasis / stress / hypobaric hypoxia / physical exercise / rats

References

[1] Glebov VV. Influence of the technogenic sphere of the big city on human adaptation processes. Fundamentalnye issledovaniya. 2013;(10–11):2461–2465. (In Russ.) EDN: RRWAAN

[2] Глебов В.В. Влияние техногенной сферы большого города на адаптационные процессы человека // Фундаментальные исследования. 2013. № 10–11. С. 2461–2465. EDN: RRWAAN

[3] Kinderlehrer DA. Inflammation as the common pathophysiology linking stress, mental illness, autoimmunity and chronic disease: Implications for public health policy. J Biomed Res Environ Sci. 2024;5(3):242–255. doi: 10.37871/jbres1757

[4] Kinderlehrer D.A. Inflammation as the common pathophysiology linking stress, mental illness, autoimmunity and chronic disease: Implications for public health policy // J Biomed Res Environ Sci. 2024. Vol. 5, N. 3. Р. 242–255. doi: 10.37871/jbres1889

[5] Salukhov VV, Kharitonov MA, Varavin NA, Krasovskaya AS, Santakov AA. Impact of stress on hemostasis. Consilium Medicum. 2023;25(2):91–94. (In Russ.) doi: 10.26442/20751753.2023.2.202183

[6] Салухов В.В., Харитонов М.А., Варавин Н.А., и др. Влияние стресса на гемостаз // Consilium Medicum. 2023. Т. 25, № 2. C. 91–94. doi: 10.26442/20751753.2023.2.202183

[7] Von Känel R. Acute mental stress and hemostasis: When physiology becomes vascular harm. Thromb Res. 2015;135(1):52–55. doi: 10.1016/S0049-3848(15)50444-1

[8] Von Känel R. Acute mental stress and hemostasis: When physiology becomes vascular harm // Thromb Res. 2015. Vol. 135 (Suppl. 1). Р. S52– S55. doi: 10.1016/S0049-3848(15)50444-1

[9] Bentur OS, Sarig G, Brenner B, Jacob G. Effects of acute stress on thrombosis. Semin Thromb Hemost. 2018;44(7):662–668. doi: 10.1055/s-0038-1660853

[10] Bentur O.S., Sarig G., Brenner B., Jacob G. Effects of acute stress on thrombosis // Semin Thromb Hemost. 2018. Vol. 44, N. 7. P. 662–668. doi: 10.1055/s-0038-1660853

[11] Sandrini L, Ieraci A, Amadio P, Zarà M, Barbieri SS. Impact of acute and chronic stress on thrombosis in healthy individuals and cardiovascular disease patients. Int J Mol Sci. 2020;21(21):7818. doi: 10.3390/ijms21217818

[12] Sandrini L., Ieraci A., Amadio P., et al. Impact of acute and chronic stress on thrombosis in healthy individuals and cardiovascular disease patients // Int J Mol Sci. 2020. Vol. 21, N. 21. Р. 7818. doi: 10.3390/ijms21217818

[13] Lee BJ, Gibson OR, Thake CD, Tipton M, Hawley JA, Cotter JD. Editorial: Cross adaptation and cross tolerance in human health and disease. Front Physiol. 2019;9:1827. doi: 10.3389/fphys.2018.01827

[14] Lee B.J., Gibson O.R., Thake C.D., et al. Editorial: Cross adaptation and cross tolerance in human health and disease // Frontiers in Physiology. 2019. Vol. 9. P. 1827. doi: 10.3389/fphys.2018.01827

[15] Stromsnes K, Correas AG, Lehmann J, Gambini J, Olaso-Gonzalez G. Anti-inflammatory properties of diet: Role in healthy aging. Biomedicines. 2021;9(8):922. doi: 10.3390/biomedicines9080922

[16] Stromsnes K., Correas A.G., Lehmann J., et al. Anti-inflammatory properties of diet: Role in healthy aging // Biomedicines. 2021. Vol. 9, N. 8. Р. 922. doi: 10.3390/biomedicines9080922

[17] Shakhmatov II, Alekseyeva OV, Kiselyov VI. Physical training alters the reactions of the hemostasis system to hypoxia. Bulletin of Siberian medicine. 2010;9(1):58–62. (In Russ.) EDN: LLOYNB

[18] Шахматов И.И., Алексеева О.В., Киселев В.И. Влияние физических тренировок на реакции системы гемостаза при воздействии гипоксии // Бюллетень сибирской медицины. 2010. Т. 9, № 1. С. 58–62. EDN: LLOYNB

[19] Hinkelbein J, Jansen S, Iovino I, Kruse S, Meyer M, Cirillo F, Drinhaus H, Hohn A, Klein C, Robertis E, Beutner D. Thirty minutes of hypobaric hypoxia provokes alterations of immune response, haemostasis, and metabolism proteins in human serum. Int J Mol Sci. 2017;18(9):1882. doi: 10.3390/ijms18091882

[20] Hinkelbein J., Jansen S., Iovino I., et al. Thirty minutes of hypobaric hypoxia provokes alterations of immune response, haemostasis, and metabolism proteins in human serum // Int J Mol Sci. 2017. Vol. 18, N. 9. Р. 1882. doi: 10.3390/ijms18091882

[21] Schmitz J, Kolaparambil Varghese LJ, Liebold F, Meyer M, Nerlich L, Starck C, Thierry S, Jansen S, Hinkelbein J. Influence of 30 and 60 min of hypobaric hypoxia in simulated altitude of 15,000 ft on human proteome profile. Int J Mol Sci. 2022;23(7):3909. doi: 10.3390/ijms23073909

[22] Schmitz J., Kolaparambil Varghese L.J., Liebold F., et al. Influence of 30 and 60 min of hypobaric hypoxia in simulated altitude of 15,000 ft on human proteome profile // Int J Mol Sci. 2022. Vol. 23, N. 7. Р. 3909. doi: 10.3390/ijms23073909

[23] Shakhmatov II, Kiselev VI. The effect of short-term stress on hemostasis in rats. Kazan Medical Journal. 2010;91(4):464–467. (In Russ.) EDN: MVGHHV

[24] Шахматов И.И., Киселев В.И. Влияние кратковременного стресса на гемостаз у крыс // Казанский медицинский журнал. 2010. Т. 91, № 4. С. 464–467. EDN: MVGHHV

[25] Moskalenko SV, Shakhmatov II, Bondarchuk YuA, Alekseeva OV, Ulitina OM. Reaction of hemostasis system in hypercapnic hypoxia after the course of mexidol assessed by the method of thromboelastography. Kazan Medical Journal. 2018;99(6):936–941. (In Russ.) doi: 10.17816/KMJ2018-936

[26] Москаленко С.В., Шахматов И.И., Бондарчук Ю.А., и др. Реакция системы гемостаза при гиперкапнической гипоксии после курсового применения мексидола с использованием метода тромбоэластографии // Казанский медицинский журнал. 2018. Т. 99, № 6. С. 936–941. doi: 10.17816/KMJ2018-936

[27] Zenko MY, Rybnikova EA. Cross adaptation: from F.Z. Meerson to the modern state of the problem. Part 1. Adaptation, cross-adaptation and cross-sensitization. Uspekhi fiziologicheskikh nauk. 2019;50(4):3–13. (In Russ.) doi: 10.1134/S0301179819040088

[28] Зенько М.Ю., Рыбникова Е.А. Перекрёстная адаптация: от Ф.З. Меерсона до наших дней. Часть 1. Адаптация, перекрёстная адаптация и перекрёстная сенсибилизация // Успехи физиологических наук. 2019. Т. 50, № 4. С. 3–13. doi: 10.1134/S0301179819040088

[29] Obraztsova LA, Bondarchuk YA, Shakhmatov II, Manaeva IN, Lisina SV. The role of plant adaptogen in the correction of parameters of the hemostasis system during emotional-immobilization stress in the experiment. Kazan Medical Journal. 2023;104(5):709–715. (In Russ.) doi: 10.17816/KMJ217671

[30] Образцова Л.А., Бондарчук Ю.А., Шахматов И.И., и др. Роль растительного адаптогена в коррекции параметров системы гемостаза при эмоционально-иммобилизационном стрессе в эксперименте // Казанский медицинский журнал. 2023. Т. 104, № 5. С. 709–715. doi: 10.17816/KMJ217671

[31] Momot AP, Tsyvkina LP, Taranenko IA, Mamaev AN, Serdyuk GV, Shakhmatov II, Lydina IV, Grigor'eva EV, Belozerov DE, Nikitina DA, Strozenko LA, Petrekova OV, Bespalova OV, Lomaev IS. Sovremennye metody raspoznavaniya sostoyaniya tromboticheskoi gotovnosti. Monografiya. (Modern methods of recognition of the state of thrombotic readiness. Monograph.) AP Momot, editor. Moscow: Znanie-M; 2022. 146 p. (In Russ.) EDN: GLULSH

[32] Момот А.П., Цывкина Л.П., Тараненко И.А., и др. Современные методы распознавания состояния тромботической готовности. Монография / Под науч. ред. А.П. Момота. Москва: Знание-М, 2022. 146 с. EDN: GLULSH

[33] Kuznik BI. Kletochnye i molekulyarnye mekhanizmy regulyatsii sistemy gemostaza v norme i patologii. Monografiya. (Cellular and molecular mechanisms of regulation of the hemostasis system in health and disease. Monograph.) Chita: Ekspress-izdatel'stvo; 2010. 832 p. (In Russ.) EDN: TGKCAH

[34] Кузник Б.И. Клеточные и молекулярные механизмы регуляции системы гемостаза в норме и патологии. Монография. Чита: Экспресс-издательство, 2010. 832 с. EDN: TGKCAH

[35] Yau JW, Teoh H, Verma S. Endothelial cell control of thrombosis. BMC Cardiovasc Disord. 2015;15:130. doi: 10.1186/s12872-015-0124-z

[36] Yau J.W., Teoh H., Verma S. Endothelial cell control of thrombosis // BMC Cardiovasc Disord. 2015. Vol. 15. Р. 130. doi: 10.1186/s12872-015-0124-z

[37] Olas B. Gasomediators (NO, CO, and H₂S) and their role in hemostasis and thrombosis. Clin Chim Acta. 2015;445:115–121. doi: 10.1016/j.cca.2015.03.027

[38] Olas B. Gasomediators (NO, CO, and H₂S) and their role in hemostasis and thrombosis // Clin Chim Acta. 2015. Vol. 445. Р. 115–121. doi: 10.1016/j.cca.2015.03.027

[39] Gabitov TR, Yasenyavskaya AL, Tsibizova AA. Cytokine theory of overtraining syndrome. Modern issues of biomedicine. 2022;6(4):35–41. (In Russ.) doi: 10.51871/2588-0500_2022_06_04_4

[40] Габитов Т.Р., Ясенявская А.Л., Цибизова А.А. Цитокиновая теория синдрома перетренированности // Современные вопросы биомедицины. 2022. Т. 6, № 4. С. 35–41. doi: 10.51871/2588-0500_2022_06_04_4

[41] Docherty S, Harley R, McAuley JJ, Crowe LA, Pedret C, Kirwan PD, Siebert S, Millar NL. The effect of exercise on cytokines: implications for musculoskeletal health: A narrative review. BMC Sports Sci Med Rehabilitation. 2022;14:5. doi: 10.1186/s13102-022-00397-2

[42] Docherty S., Harley R., McAuley J.J., et al. The effect of exercise on cytokines: Implications for musculoskeletal health: a narrative review // BMC Sports Science, Medicine and Rehabilitation. 2022. Vol. 14. P. 5. doi: 10.1186/s13102-022-00397-2

[43] Kuznik BI. Cytokines and hemostasis. I. Cytokines and vascular platelet hemostasis. Thrombosis, hemostasis and rheology. 2012;(2):12–23. (In Russ.) EDN: OYRBOT

[44] Кузник Б.И. Цитокины и система гемостаза. I. Цитокины и сосудисто-тромбоцитарный гемостаз // Тромбоз, гемостаз и реология. 2012. № 2. С. 12–23. EDN: OYRBOT

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