Theoretical background of hypoxytherapy

Abstract

The review discusses the structure and physiology of the oxygen supply functional system and its self-regulatory potential and role in maintaining the body’s optimal metabolic homeostasis level of blood gases. Up-to-date data on the functioning of peripheral (arterial) and central (medullary) chemoreceptors, molecular mechanisms of the oxygen and carbon dioxide content and pH perception, and their association with afferent nerve endings are presented. The paths and centers of the chemosensory reflex in various brain regions, effector elements, and reverse afferentation mechanisms are shown. Response patterns to exogenous and endogenous hypoxic stimuli from the various elements of the oxygen supply system are described. The role of intracellular HIF-dependent and HIF-independent pathways in adaptive reactions for maintaining an optimal intracellular metabolism is demonstrated. Cell mechanisms with adaptive roles in hypoxia/reoxygenation under the conditions of interval normobaric hypoxic therapy are discussed.

The review of current concepts and analysis of research results on the physiology of the oxygen supply functional system, its structural and functional status, and its molecular regulation under exogenous hypoxic conditions will draw attention to the expediency of further randomized clinical trials on interval normobaric hypoxytherapy as a rehabilitation method for patients with chronic cardiovascular diseases

Keywords

oxygen supply functional system / chemosensory reflex / adaptive mechanisms / hypoxia/reoxygenation

References

[1] Sayutina EV, Osadchuk MA, Romanov BK, et al. Cardiac rehabilitation and secondary prevention after acute myocardial infarction: a modern view on the problem. Medical Journal of the Russian Federationn Journal. 2021;27(6):571–587. (In Russ). doi: 10.17816/0869-2106-2021-27-6-571-587

[2] Саютина Е.В., Осадчук М.А., Романов Б.К., и др. Кардиореабилитация и вторичная профилактика после перенесённого острого инфаркта миокарда: современный взгляд на проблему // Российский медицинский журнал. 2021. Т. 27, № 6. С. 571–587. doi: 10.17816/0869-2106-2021-27-6-571-587

[3] Mc Namara K, Alzubaidi H, Jackson JK. Cardiovascular disease as a leading cause of death: how are pharmacists getting involved? Integr Pharm Res Pract. 2019;8:1–11. doi: 10.2147/IPRP.S133088

[4] Mc Namara K., Alzubaidi H., Jackson J.K. Cardiovascular disease as a leading cause of death: how are pharmacists getting involved? // Integr Pharm Res Pract. 2019. Vol. 8. P. 1–11. doi: 10.2147/IPRP.S133088

[5] Timmis A, Vardas P, Townsend N, et al. European Society of Cardiology: cardiovascular disease statistics 2021. Eur Heart J. 2022;43(8):716–799. doi: 10.1093/eurheartj/ehab892

[6] Timmis A., Vardas P., Townsend N., et al. European Society of Cardiology: cardiovascular disease statistics 2021 // Eur Heart J. 2022. Vol. 43, N 8. P. 716–799. doi: 10.1093/eurheartj/ehab892

[7] Kim IV, Bochkareva EV, Varakin YuYa. The unity of approaches to preventing coronary heart disease and cerebrovascular diseases. The Russian Journal of Preventive Medicine. 2015;18(6):24–33. (In Russ). doi: 10.17116/profmed201518624-33

[8] Ким И.В., Бочкарева Е.В., Варакин Ю.Я. Единство подходов к профилактике ишемической болезни сердца и цереброваскулярных заболеваний // Профилактическая медицина. 2015. Т. 18, № 6. С. 24–33. doi: 10.17116/profmed201518624-33

[9] Glushchenko VA, Irklienko EK. Cardiovascular morbidity — one of the most vital problems of modern health care. Medicine and Health Care Organization. 2019;4(1):56–63. (In Russ).

[10] Глущенко В.А., Ирклиенко Е.К. Сердечно-сосудистая заболеваемость — одна из важнейших проблем здравоохранения // Медицина и организация здравоохранения. 2019. Т. 4, № 1. С. 56–63.

[11] Tolpygina SN, Martsevich SYu. Investigation of CHD PROGNOSIS: new long-term follow-up data. The Russian Journal of Preventive Medicine. 2016;19(1):30–36. (In Russ). doi: 10.17116/profmed201619130-36

[12] Толпыгина С.Н., Марцевич С.Ю. Исследование ПРОГНОЗ ИБС. Новые данные по отдаленному наблюдению // Профилактическая медицина. 2016. Т. 19, № 1. С. 30–36. doi: 10.17116/profmed201619130-36

[13] Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, et al. Endothelial dysfunction, inflammation and coronary artery disease: potential biomarkers and promising therapeutical approaches. Int J Mol Sci. 2021;22(8):3850. doi: 10.3390/ijms22083850

[14] Medina-Leyte D.J., Zepeda-García O., Domínguez-Pérez M., et al. Endothelial dysfunction, inflammation and coronary artery disease: potential biomarkers and promising therapeutical approaches // Int J Mol Sci. 2021. Vol. 22, N 8. P. 3850. doi: 10.3390/ijms22083850

[15] Bubnova MG, Aronov DM. Cardiac rehabilitation: stages, principles and international classification of functioning (ICF). The Russian Journal of Preventive Medicine. 2020;23(5):40–49. (In Russ). doi: 10.17116/profmed20202305140

[16] Бубнова М.Г., Аронов Д.М. Кардиореабилитация: этапы, принципы и международная классификация функционирования (МКФ) // Профилактическая медицина. 2020. Т. 23, № 5. С. 40–49. doi: 10.17116/profmed20202305140

[17] Aronov DM. Cardiac rehabilitation basics. Cardiology: news, opinions, training. 2016;(3):104–110. (In Russ).

[18] Аронов Д.М. Основы кардиореабилитации // Кардиология: новости, мнения, обучение. 2016. № 3. С. 104–110.

[19] Pupyreva ED, Balykin MV. Mechanism of oxygen supply in sportsmen at the rest and maximal physical exercises. Ulyanovsk Medico-biological Journal. 2013;(1):124–130. (In Russ).

[20] Пупырева Е.Д., Балыкин М.В. Механизмы кислородного обеспечения организма спортсменов в покое и при нагрузках максимальной мощности // Ульяновский медико-биологический журнал. 2013. № 1. С. 124–130.

[21] Alekseeva TM, Kovzelev PD, Topuzova MP, et al. Hypercapnic-hypoxic respiratory training as a method of post-conditioning in stroke suvivors. Arterial’naya gipertenziya. 2019;25(2):134–142. (In Russ). doi: 10.18705/1607-419X-2019-25-2-134-142

[22] Алексеева Т.М., Ковзелев П.Д., Топузова М.П., и др. Гиперкапнически-гипоксические дыхательные тренировки как потенциальный способ реабилитационного лечения пациентов, перенесших инсульт // Артериальная гипертензия. 2019. Т. 25, № 2. С. 134–142. doi: 10.18705/1607-419X-2019-25-2-134-142

[23] Nikolaeva AG. Ispol’zovanie adaptacii k gipoksii v medicine i sporte. Vitebsk: VGMU; 2015. (In Russ).

[24] Николаева А.Г. Использование адаптации к гипоксии в медицине и спорте. Витебск : ВГМУ, 2015.

[25] Ignatenko GA, Mukhin IV, Tumanova SV. Antihypertensive effectiveness of interval normobaric hypoxytherapy in patients with chronic glomerulonephritis and angina pectoris. Nephrology (Saint-Petersburg). 2007;11(3):64–69. (In Russ).

[26] Игнатенко Г.А., Мухин И.В., Туманова С.В. Антигипертензивная эффективность интервальной нормобарической гипокситерапии у больных хроническим гломерулонефритом и стенокардией // Нефрология. 2007. Т. 11, № 3. С. 64–69.

[27] Ignatenko GA, Denisova EM, Sergienko NV. Hypoxytherapy as a prospective method of increasing the effectiveness of complex treatment of comorbid pathology. Vestnik neotlozhnoj i vosstanovitel’’noj hirurgii. 2021;6(4):73–80. (In Russ).

[28] Игнатенко Г.А., Денисова Е.М., Сергиенко Н.В. Гипокситерапия как перспективный метод повышения эффективности комплексного лечеия коморбидной патологии // Вестник неотложной и восстановительной хирургии. 2021. Т. 6, № 4. С. 73–80.

[29] Borukaeva IKh, Abazova ZKh, Ivanov AB, Shkhagumov KYu. The role of interval hypoxytherapy and enteral oxygen therapy in the rehabilitation of the patients presenting with chronic obstructive pulmonary disease. Problems of Balneology, Physiotherapy and Exercise Therapy. 2019;96(2):27–32. (In Russ). doi: 10.17116/kurort20199602127

[30] Борукаева И.Х., Абазова З.Х., Иванов А.Б., Шхагумов К.Ю. Интервальная гипокситерапия и энтеральная оксигенотерапия в реабилитации пациентов с хронической обструктивной болезнью легких // Вопросы курортологии, физиотерапии и лечебной физической культуры. 2019. Т. 96, № 2. С. 27–32. doi: 10.17116/kurort20199602127

[31] Glazachev OS, Geppe NA, Timofeev YuS, et al. Indicators of individual hypoxia resistance — a way to optimize hypoxic training for children. Russian Bulletin of Perinatology and Pediatrics. 2020;65(4):78–84. (In Russ). doi: 10.21508/1027-4065-2020-65-4-78-84

[32] Глазачев О.С., Геппе Н.А., Тимофеев Ю.С., и др. Индикаторы индивидуальной устойчивости к гипоксии — путь оптимизации применения гипоксических тренировок у детей // Российский вестник перинатологии и педиатрии. 2020. Т. 65, № 4. С. 78–84. doi: 10.21508/1027-4065-2020-65-4-78-84

[33] Ignatenko GA, Mukhin IV, Zubritskiy KS, et al. Influence of different therapy modes on the manifestation of arythmic syndrome in patients with type 2 diabetes mellitus. Mediko-social’nye problemy sem’i. 2021;26(4):49–56. (In Russ).

[34] Игнатенко Г.А., Мухин И.В., Зубрицкий К.С., и др. Влияние разных режимов терапии на проявления аритмического синдрома у больных сахарным диабетом 2-го типа // Медико-социальные проблемы семьи. 2021. Т. 26, № 4. С. 49–56.

[35] Zaletova TS. Interval hypoxic therapy in cardiology and dietetics. Medicine. Sociology. Philosophy. Applied research. 2022;4:32–34. (In Russ).

[36] Залетова Т.С. Интервальная гипоксическая терапия в кардиологии и диетологии // Медицина. Социология. Философия. Прикладные исследования. 2022. № 4. С. 32–34.

[37] Ignatenko GA, Dubovaya AV, Naumenko YuV. Treatment potential of normobaric hypoxic therapy in therapeutic and pediatric practice. Russian Bulletin of Perinatology and Pediatrics. 2022;67(6):46–53. (In Russ). doi: 10.21508/1027-4065-2022-67-6-46-53

[38] Игнатенко Г.А., Дубовая А.В., Науменко Ю.В. Возможности применения нормобарической гипокситерапии в терапевтической и педиатрической практиках // Российский вестник перинатологии и педиатрии. 2022. Т. 67, № 6. С. 46–53. doi: 10.21508/1027-4065-2022-67-6-46-53

[39] Navarrete-Opazo A, Mitchell GS. Recruitment and plasticity in diaphragm, intercostal, and abdominal muscles in unanesthetized rats. J Appl Physiol (1985). 2014;117(2):180–188. doi: 10.1152/japplphysiol.00130.2014

[40] Navarrete-Opazo A., Mitchell G.S. Recruitment and plasticity in diaphragm, intercostal, and abdominal muscles in unanesthetized rats // J Appl Physiol (1985). 2014. Vol. 117, N 2. P. 180–188. doi: 10.1152/japplphysiol.00130.2014

[41] Rozova EV, Mankovskaya IN, Mironova GD. Structural and dynamic changes in mitochondria of rat myocardium under acute hypoxic hypoxia: role of mitochondrial ATP-dependent potassium channel. Biochemistry (Mosc). 2015;80(8):994–1000. doi: 10.1134/S0006297915080040

[42] Rozova E.V., Mankovskaya I.N., Mironova G.D. Structural and dynamic changes in mitochondria of rat myocardium under acute hypoxic hypoxia: role of mitochondrial ATP-dependent potassium channel // Biochemistry (Mosc). 2015. Vol. 80, N 8. P. 994–1000. doi: 10.1134/S0006297915080040

[43] Vogtel M, Michels A. Role of intermittent hypoxia in the treatment of bronchial asthma and chronic obstructive pulmonary disease. Curr Opin Allergy Clin Immunol. 2010;10(3):206–213. doi: 10.1097/ACI.0b013e32833903a6

[44] Vogtel M., Michels A. Role of intermittent hypoxia in the treatment of bronchial asthma and chronic obstructive pulmonary disease // Curr Opin Allergy Clin Immunol. 2010. Vol. 10, N 3. P. 206–213. doi: 10.1097/ACI.0b013e32833903a6

[45] https://libmonster.com/index.php [Internet]. Sudakov K. Functional systems of the organism. London: Libmonster; 2018 [cited: 2023 May 11]. Available from: https://libmonster.com/m/articles/view/FUNCTIONAL-SYSTEMS-OF-THE-ORGANISM/

[46] https://libmonster.com/index.php [интернет]. Sudakov K. Functional systems of the organism. London: Libmonster, 2018 [дата обращения: 11.05.2023]. Доступ по ссылке: https://libmonster.com/m/articles/view/FUNCTIONAL-SYSTEMS-OF-THE-ORGANISM/

[47] Injarabian L, Scherlinger M, Devin A, et al. Ascorbate maintains a low plasma oxygen level. Sci Rep. 2020;10(1):10659. doi: 10.1038/s41598-020-67778-w

[48] Injarabian L., Scherlinger M., Devin A., et al. Ascorbate maintains a low plasma oxygen level // Sci Rep. 2020. Vol. 10, N 1. P. 10659. doi: 10.1038/s41598-020-67778-w

[49] Iturriaga R, Alcayaga J, Chapleau MW, Somers VK. Carotid body chemoreceptors: physiology, pathology, and implications for health and disease. Physiol Rev. 2021;101(3):1177–1235. doi: 10.1152/physrev.00039.2019

[50] Iturriaga R., Alcayaga J., Chapleau M.W., Somers V.K. Carotid body chemoreceptors: physiology, pathology, and implications for health and disease // Physiol Rev. 2021. Vol. 101, N 3. P. 1177–1235. doi: 10.1152/physrev.00039.2019

[51] Milloy KM, White MG, Chicilo JOC, et al. Assessing central and peripheral respiratory chemoreceptor interaction in humans. Exp Physiol. 2022;107(9):1081–1093. doi: 10.1113/EP089983

[52] Milloy K.M., White M.G., Chicilo J.O.C., et al. Assessing central and peripheral respiratory chemoreceptor interaction in humans // Exp Physiol. 2022. Vol. 107, N 9. P. 1081–1093. doi: 10.1113/EP089983

[53] Prabhakar NR, Peng YJ, Yuan G, Nanduri J. Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia. Cell Tissue Res. 2018;372(2):427–431. doi: 10.1007/s00441-018-2807-0

[54] Prabhakar N.R., Peng Y.J., Yuan G., Nanduri J. Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia // Cell Tissue Res. 2018. Vol. 372, N 2. P. 427–431. doi: 10.1007/s00441-018-2807-0

[55] Prabhakar NR, Semenza GL. Regulation of carotid body oxygen sensing by hypoxia-inducible factors. Pflugers Arch. 2016;468(1): 71–75. doi: 10.1007/s00424-015-1719-z

[56] Prabhakar N.R., Semenza G.L. Regulation of carotid body oxygen sensing by hypoxia-inducible factors // Pflugers Arch. 2016. Vol. 468, N 1. P. 71–75. doi: 10.1007/s00424-015-1719-z

[57] Semenza GL, Prabhakar NR. The role of hypoxia-inducible factors in carotid body (patho) physiology. J Physiol. 2018;596(15): 2977–2983. doi: 10.1113/JP275696

[58] Semenza G.L., Prabhakar N.R. The role of hypoxia-inducible factors in carotid body (patho) physiology // J Physiol. 2018. Vol. 596, N 15. P. 2977–2983. doi: 10.1113/JP275696

[59] López-Barneo J. Neurobiology of the carotid body. Handb Clin Neurol. 2022;188:73–102. doi: 10.1016/B978-0-323-91534-2.00010-2

[60] López-Barneo J. Neurobiology of the carotid body // Handb Clin Neurol. 2022. Vol. 188. P. 73–102. doi: 10.1016/B978-0-323-91534-2.00010-2

[61] Guyenet PG, Stornetta RL, Souza GMR, et al. The retrotrapezoid nucleus: central chemoreceptor and regulator of breathing automaticity. Trends Neurosci. 2019;42(11):807–824. doi: 10.1016/j.tins.2019.09.002

[62] Guyenet P.G., Stornetta R.L., Souza G.M.R., et al. The retrotrapezoid nucleus: central chemoreceptor and regulator of breathing automaticity // Trends Neurosci. 2019. Vol. 42, N 11. P. 807–824. doi: 10.1016/j.tins.2019.09.002

[63] Gorodeckaya IV. Fiziologiya dyhaniya. Vitebsk: VGMU; 2012. (In Russ).

[64] Городецкая И.В. Физиология дыхания. Витебск: ВГМУ, 2012.

[65] Safonov VA. Regulyaciya vneshnego dyhaniya. Surgut State University Journal. 2009;(2):25–34. (In Russ).

[66] Сафонов В.А. Регуляция внешнего дыхания // Вестник Сургутского государственного университета. 2009. № 2. С. 25–34.

[67] Prikhodko VA, Selizarova NO, Okovityi SV. Molecular mechanisms for hypoxia development and adaptation to it. Part I. Arkhiv Patologii. 2021;83(2):52–61. (In Russ). doi: 10.17116/patol20218302152

[68] Приходько В.А., Селизарова Н.О., Оковитый С.В. Молекулярные механизмы развития гипоксии и адаптации к ней. Часть I // Архив патологии. 2021. Т. 83, № 2. С. 52–61. doi: 10.17116/patol20218302152

[69] López-Barneo J, Ortega-Sáenz P. Mitochondrial acute oxygen sensing and signaling. Crit Rev Biochem Mol Biol. 2022;57(2): 205–225. doi: 10.1080/10409238.2021.2004575

[70] López-Barneo J., Ortega-Sáenz P. Mitochondrial acute oxygen sensing and signaling // Crit Rev Biochem Mol Biol. 2022. Vol. 57, N 2. P. 205–225. doi: 10.1080/10409238.2021.2004575

[71] Iturriaga R, Del Rio R, Alcayaga J. Carotid body inflammation: role in hypoxia and in the anti-inflammatory reflex. Physiology (Bethesda). 2022;37(3):128–140. doi: 10.1152/physiol.00031.2021

[72] Iturriaga R., Del Rio R., Alcayaga J. Carotid body inflammation: role in hypoxia and in the anti-inflammatory reflex // Physiology (Bethesda). 2022. Vol. 37, N 3. P. 128–140. doi: 10.1152/physiol.00031.2021

[73] Zera T, Moraes DJA, da Silva MP, et al. The logic of carotid body connectivity to the brain. Physiology (Bethesda). 2019;34(4):264–282. doi: 10.1152/physiol.00057.2018

[74] Zera T., Moraes D.J.A., da Silva M.P., et al. The logic of carotid body connectivity to the brain // Physiology (Bethesda). 2019. Vol. 34, N 4. P. 264–282. doi: 10.1152/physiol.00057.2018

[75] Iturriaga R. Translating carotid body function into clinical medicine. J Physiol. 2018;596(15):3067–3077. doi: 10.1113/JP275335

[76] Iturriaga R. Translating carotid body function into clinical medicine // J Physiol. 2018. Vol. 596, N 15. P. 3067–3077. doi: 10.1113/JP275335

[77] Morin R, Goulet N, Mauger JF, Imbeault P. Physiological responses to hypoxia on triglyceride levels. Front Physiol. 2021;23(12):730935. doi: 10.3389/fphys.2021.730935

[78] Morin R., Goulet N., Mauger J.F., Imbeault P. Physiological responses to hypoxia on triglyceride levels // Front Physiol. 2021. Vol. 12. P. 730935. doi: 10.3389/fphys.2021.730935

[79] Salvagno M, Coppalini G, Taccone FS, et al. The normobaric oxygen paradox-hyperoxic hypoxic paradox: a novel expedient strategy in hematopoiesis clinical issues. Int J Mol Sci. 2023;24(1):82. doi: 10.3390/ijms24010082

[80] Salvagno M., Coppalini G., Taccone F.S., et al. The normobaric oxygen paradox: hyperoxic hypoxic paradox: a novel expedient strategy in hematopoiesis clinical issues // Int J Mol Sci. 2023. Vol. 24, N 1. P. 82. doi: 10.3390/ijms24010082

[81] Bondarenko NN, Khomutov EV, Ryapolova TL, et al. Molecular and cellular mechanisms of hypoxic response. Ulyanovsk Medico-biological Journal. 2023;(2):6–29. (In Russ). doi: 10.34014/2227-1848-2023-2-6-29

[82] Бондаренко Н.Н., Хомутов Е.В., Ряполова Т.Л., и др. Молекулярно-клеточные механизмы ответа организма на гипоксию // Ульяновский медико-биологический журнал. 2023. № 2. С. 6–29. doi: 10.34014/2227-1848-2023-2-6-29

[83] Prabhakar NR, Semenza GL. Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2. Physiol Rev. 2012;92(3):967–1003. doi: 10.1152/physrev.00030.2011

[84] Prabhakar N.R., Semenza G.L. Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2 // Physiol Rev. 2012. Vol. 92, N 3. P. 967–1003. doi: 10.1152/physrev.00030.2011

[85] Choudhry H, Harris AL. Advances in hypoxia-inducible factor biology. Cell Metab. 2018;27(2):281–298. doi: 10.1016/j.cmet.2017.10.005

[86] Choudhry H., Harris A.L. Advances in hypoxia-inducible factor biology // Cell Metab. 2018. Vol. 27, N 2. P. 281–298. doi: 10.1016/j.cmet.2017.10.005

[87] Liu Z, Wu Z, Fan Y, Fang Y. An overview of biological research on hypoxia-inducible factors (HIFs). Endokrynol Pol. 2020;71(5):432–440. doi: 10.5603/EP.a2020.0064

[88] Liu Z., Wu Z., Fan Y., Fang Y. An overview of biological research on hypoxia-inducible factors (HIFs) // Endokrynol Pol. 2020. Vol. 71, N 5. P. 432–440. doi: 10.5603/EP.a2020.0064

[89] Zhang L, Cao Y, Guo X, et al. Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma. J Zhejiang Univ Sci B. 2023;24(1):32–49. doi: 10.1631/jzus.B2200269

[90] Zhang L., Cao Y., Guo X., et al. Hypoxia-induced ROS aggravate tumor progression through HIF-1α-SERPINE1 signaling in glioblastoma // J Zhejiang Univ Sci B. 2023. Vol. 24, N 1. P. 32–49. doi: 10.1631/jzus.B2200269

[91] Puri Sh, Panza G, Mateika JH. A comprehensive review of respiratory, autonomic and cardiovascular responses to intermittent hypoxia in humans. Exp Neurol. 2021;341:113709. doi: 10.1016/j.expneurol.2021.113709

[92] Puri Sh., Panza G., Mateika J.H. A comprehensive review of respiratory, autonomic and cardiovascular responses to intermittent hypoxia in humans // Exp Neurol. 2021. Vol. 341. P. 113709. doi: 10.1016/j.expneurol.2021.113709

[93] Cai M, Chen X, Shan J, et al. intermittent hypoxic preconditioning: a potential new powerful strategy for COVID-19 rehabilitation. Front Pharmacol. 2021;12:643619. doi: 10.3389/fphar.2021.643619

[94] Cai M., Chen X., Shan J., et al. Intermittent hypoxic preconditioning: a potential new powerful strategy for COVID-19 rehabilitation // Front Pharmacol. 2021. Vol. 12. P. 643619. doi: 10.3389/fphar.2021.643619

[95] Prabhakar NR, Peng YJ, Nanduri J. Adaptive cardiorespiratory changes to chronic continuous and intermittent hypoxia. Handb Clin Neurol. 2022;188:103–123. doi: 10.1016/B978-0-323-91534-2.00009-6

[96] Prabhakar N.R., Peng Y.J., Nanduri J. Adaptive cardiorespiratory changes to chronic continuous and intermittent hypoxia // Handb Clin Neurol. 2022. Vol. 188. P. 103–123. doi: 10.1016/B978-0-323-91534-2.00009-6

[97] Mansfield KD, Guzy RD, Pan Y, et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation. Cell Metab. 2005;1(6):393–399. doi: 10.1016/j.cmet.2005.05.003

[98] Mansfield K.D., Guzy R.D., Pan Y., et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs cellular oxygen sensing and hypoxic HIF-alpha activation // Cell Metab. 2005. Vol. 1, N 6. P. 393–399. doi: 10.1016/j.cmet.2005.05.003

[99] Reiterer M, Eakin A, Johnson RS, Branco CM. Hyperoxia reprogrammes microvascular endothelial cell response to hypoxia in an organ-specific manner. Cells. 2022;11(16):2469. doi: 10.3390/cells11162469

[100] Reiterer M., Eakin A., Johnson R.S., Branco C.M. Hyperoxia reprogrammes microvascular endothelial cell response to hypoxia in an organ-specific manner // Cells. 2022. Vol. 11, N 16. P. 2469. doi: 10.3390/cells11162469

[101] Sprick JD, Mallet RT, Przyklenk K, Rickards CA. Ischaemic and hypoxic conditioning: potential for protection of vital organs. Exp Physiol. 2019;104(3):278–294. doi: 10.1113/EP087122

[102] Sprick J.D., Mallet R.T., Przyklenk K., Rickards C.A. Ischaemic and hypoxic conditioning: potential for protection of vital organs // Exp Physiol. 2019. Vol. 104, N 3. P. 278–294. doi: 10.1113/EP087122

[103] Ashagre SM, Borukaeva IH. Effect of reduced oxygen content in inhaled air in a hypoxic test on hypertensive patients. Modern problems of science and education. 2022;(3):99. (In Russ). doi: 10.17513/spno.31725

[104] Ашагре С.М., Борукаева И.Х. Действие пониженного содержания кислорода во вдыхаемом воздухе в гипоксическом тесте на больных гипертонической болезнью // Современные проблемы науки и образования. 2022. № 3. С. 99. doi: 10.17513/spno.31725

[105] Brugniaux JV, Coombs GB, Barak OF, et al. Highs and lows of hyperoxia: physiological, performance, and clinical aspects. Am J Physiol Regul Integr Comp Physiol. 2018;315(1):R1–R27. doi: 10.1152/ajpregu.00165.2017

[106] Brugniaux J.V., Coombs G.B., Barak O.F., et al. Highs and lows of hyperoxia: physiological, performance, and clinical aspects // Am J Physiol Regul Integr Comp Physiol. 2018. Vol. 315, N 1. P. R1–R27. doi: 10.1152/ajpregu.00165.2017

[107] Kutepov DE, Zhigalova MS, Pasechnik IN. Pathogenesis of ischemia/reperfusion syndrome. Kazan Medical Journal. 2018;99(4):640–644. (In Russ). doi: 10.17816/KMJ2018-640

[108] Кутепов Д.Е., Жигалова М.С., Пасечник И.Н. Патогенез синдрома ишемии-реперфузии // Казанский медицинский журнал. 2018. Т. 99, № 4. С. 640–644. doi: 10.17816/KMJ2018-640

[109] Soares ROS, Losada DM, Jordani MC, et al. Ischemia/reperfusion injury revisited: an overview of the latest pharmacological strategies. Int J Mol Sci. 2019;20(20):5034. doi: 10.3390/ijms20205034

[110] Soares R.O.S., Losada D.M., Jordani M.C., et al. Ischemia/reperfusion injury revisited: an overview of the latest pharmacological strategies // Int J Mol Sci. 2019. Vol. 20, N 20. P. 5034. doi: 10.3390/ijms20205034

[111] Neimark MI. Ischemia-reperfusion syndrome. Pirogov Russian Journal of Surgery. 2021;(9):71–76. (In Russ). doi: 10.17116/hirurgia202109171

[112] Неймарк М.И. Синдром ишемии-реперфузии // Хирургия. Журнал имени Н.И. Пирогова. 2021. № 9. С. 71–76. doi: 10.17116/hirurgia202109171

[113] Minakina LN, Goldapel EG, Usov LA. The influence of adenosine receptor ligands and hypoxic preconditioning on the metabolism of the brain tissue in the experiment. S.S. Korsakov Journal of Neurology and Psychiatry. 2018;118(7):54–58. (In Russ). doi: 10.17116/jnevro20181187154

[114] Минакина Л.Н., Гольдапель Э.Г., Усов Л.А. Влияние лигандов аденозиновых рецепторов и гипоксического прекондиционирования на показатели основного обмена мозговой ткани в эксперименте // Журнал неврологии и психиатрии имени С.С. Корсакова. 2018. Т. 118, № 7. С. 54–58. doi: 10.17116/jnevro20181187154

[115] Ma C, Zhao Y, Ding X, Gao B. Hypoxic training ameliorates skeletal muscle microcirculation vascular function in a Sirt3-dependent manner. Front Physiol. 2022;13:921763. doi: 10.3389/fphys.2022.921763

[116] Ma C., Zhao Y., Ding X., Gao B. Hypoxic training ameliorates skeletal muscle microcirculation vascular function in a Sirt3-dependent manner // Front Physiol. 2022. Vol. 13. P. 921763. doi: 10.3389/fphys.2022.921763

[117] Lukyanova LD, Kirova YI. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia. Front Neurosci. 2015;9:320. doi: 10.3389/fnins.2015.00320

[118] Lukyanova L.D., Kirova Y.I. Mitochondria-controlled signaling mechanisms of brain protection in hypoxia // Front Neurosci. 2015. Vol. 9. P. 320. doi: 10.3389/fnins.2015.00320

[119] Hess ML, Manson NH. Molecular oxygen: friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury. J Mol Cell Cardiol. 1984;16(11):969–985. doi: 10.1016/s0022-2828(84)80011-5

[120] Hess M.L., Manson N.H. Molecular oxygen: friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox and ischemia/reperfusion injury // J Mol Cell Cardiol. 1984. Vol. 16, N 11. P. 969–985. doi: 10.1016/s0022-2828(84)80011-5

[121] Milliken AS, Nadtochiy SM, Brookes PS. Inhibiting succinate release worsens cardiac reperfusion injury by enhancing mitochondrial reactive oxygen species generation. J Am Heart Assoc. 2022;11(13):e026135. doi: 10.1161/JAHA.122.026135

[122] Milliken A.S., Nadtochiy S.M., Brookes P.S. Inhibiting succinate release worsens cardiac reperfusion injury by enhancing mitochondrial reactive oxygen species generation // J Am Heart Assoc. 2022. Vol. 11, N 13. P. e026135. doi: 10.1161/JAHA.122.026135.

[123] Prag HA, Gruszczyk AV, Huang MM, et al. Mechanism of succinate efflux upon reperfusion of the ischaemic heart. Cardiovasc Res. 2021;117(4):1188–1201. doi: 10.1093/cvr/cvaa148

[124] Prag H.A., Gruszczyk A.V., Huang M.M., et al. Mechanism of succinate efflux upon reperfusion of the ischaemic heart // Cardiovasc Res. 2021. Vol. 117, N 4. P. 1188–1201. doi: 10.1093/cvr/cvaa148

RIGHTS & PERMISSIONS

Eco-Vector