CardioSomaticsCardioSomaticsCardioСоматика2221-71852658-5707Eco-Vector64291310.17816/CS642913GLCWHWReviewsОбзорыReview ArticleIntermittent hypoxic training as a rehabilitation method for patients with cardiovascular diseases: a reviewИнтервальные гипоксические тренировки как метод реабилитации пациентов с сердечно-сосудистыми заболеваниями: обзорhttps://orcid.org/0000-0002-2452-11053024-7503NagovitsinAleksandr K.НаговицинАлександр Константинович
Russian Federation
nagovizinak@gmail.comhttps://orcid.org/0000-0003-0236-24118518-0355KotovaYuliya A.КотоваЮлия Александровна
Russian Federation

MD, Dr. Sci. (Medicine), Assistant Professor

д-р мед. наук, доцент

kotova_u@inbox.ruVoronezh State Medical UniversityВоронежский государственный медицинский университет имени Н.Н. Бурденко19012026130220261643423511712202409122025Copyright ©; 2025, Eco-VectorCopyright ©; 2025, ООО "Эко-Вектор"2025Eco-VectorООО "Эко-Вектор"https://eco-vector.com/for_authors.php#07https://cardiosomatics.ru/2221-7185/article/view/642913

Ensuring the full restoration of the body’s functional capacity is a primary goal of medical rehabilitation. The introduction of new rehabilitation methods into clinical practice makes it possible to achieve substantial progress in the treatment and prevention of diseases. This may be associated with greater effectiveness of specific techniques, simplicity and safety of their application (which improves patient adherence), and their economic accessibility. In recent years, increasing interest has been directed toward the effects of intermittent hypoxia on the human body. The mechanisms underlying the clinically substantial effects of intermittent hypoxic training have been described at various levels, ranging from the regulation of gene expression to systemic physiological responses.

Intermittent hypoxic training is a method that has found application in the prevention and treatment of a number of chronic non-communicable diseases of the cardiovascular, respiratory, and nervous systems, as well as endocrine disorders, and it also affects inflammatory and aging-related processes. Intermittent hypoxic training can be applied both at rest and during physical exercise, which enables its use in sports medicine. Over the past decade, a technique alternating periods of hypoxia and hyperoxia has been actively developed. It has been suggested that replacing normoxic periods with hyperoxic ones may increase the effectiveness of intermittent hypoxic training and reduce adverse side effects.

This article presents a review of data from Russian and international scientific data concerning the mechanisms of action of intermittent hypoxic training on the human body and the possibilities of its use in cardiovascular condition.

Обеспечение полноценного восстановления функциональных возможностей организма является основной задачей медицинской реабилитации. Внедрение новых методов реабилитации пациентов в клиническую практику позволяет добиться значительных успехов в лечении и профилактике заболеваний. Это, в свою очередь, может быть связано с большей эффективностью конкретных методик, простотой и безопасностью их применения (что увеличивает приверженность пациентов) и их экономической доступностью. За последнее время всё больший интерес вызывает влияние интервальной гипоксии на организм человека. Механизмы, благодаря которым реализуются клинически значимые эффекты интервальных гипоксических тренировок, были описаны на различных уровнях — от регуляции экспрессии генов до системных физиологических реакций.

Интервальные гипоксические тренировки являются методом, нашедшим применение в профилактике и лечении ряда хронических неинфекционных заболеваний сердечно-сосудистой, дыхательной и нервной систем, эндокринологических патологий, оказывают влияние на течение процессов воспаления и старения. Интервальные гипоксические тренировки возможно применять как в покое, так и при выполнении физической нагрузки, что позволяет использовать этот метод в спортивной медицине. В последнее десятилетие активное развитие получила методика, чередующая воздействие на организм периодов гипоксии и гипероксии. Имеются предположения, что замена периодов нормоксии на гипероксические может привести к возрастанию эффективности интервальных гипоксических тренировок и снижению негативных побочных реакций.

В данной статье приводится обзор информации, имеющейся в отечественной и зарубежной литературе, касающейся механизмов воздействия интервальных гипоксических тренировок на человеческий организм и возможностей их использования при сердечно-сосудистой патологии.

hypoxiahyperoxiarehabilitationtrainingcardiovascular diseasesгипоксиягипероксияреабилитациятренировкасердечно-сосудистые заболеванияAronov DM, Bubnova MG, Drapkina OM. Non-pharmacological therapy of patients with cardiovascular diseases in cardiac rehabilitation programs. Profilakticheskaya meditsina. 2020;23(6-2):57–64. doi: 10.17116/profmed20202306257 EDN: BRBEUTHansen D, Abreu A, Ambrosetti M, et al. Exercise intensity assessment and prescription in cardiovascular rehabilitation and beyond: why and how: a position statement from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol. 2022;29(1):230–245. doi: 10.1093/eurjpc/zwad397Ambrosetti M, Abreu A, Corrà U, et al. Secondary prevention through comprehensive cardiovascular rehabilitation: From knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol. 2021;28(5):460–495. doi: 10.1177/2047487320913379 EDN: XKWALSDoimo S, Fabris E, Piepoli M, et al. Impact of ambulatory cardiac rehabilitation on cardiovascular outcomes: a long-term follow-up study. Eur Heart J. 2019;40:678–685. doi: 10.1093/eurheartj/ehy417 EDN: NXYVOKBurtscher M, Gatterer H, Szubski C, Pierantozzi E, Faulhaber M. Effects of interval hypoxia on exercise tolerance: special focus on patients with CAD or COPD. Sleep Breath. 2010;14(3):209–220. doi: 10.1007/s11325-009-0289-8 EDN: OLPZSBGlazachev OS, Zvenigorodskaja LA, Dudnik EN, et al. Interval hypo-hyperoxic training in the treatment of metabolic syndrome. Experimental and clinical gastroenterology journal. 2010;(7):51–56. EDN: MVAJUHGlazachev OS, Pozdnyakov YuM, Urinskyi AM, Zabashta SP. Hypoxia-hyperoxia adaptation and increased exercise capacity in patients with coronary heart disease. Cardiovascular Therapy and Prevention. 2014;13(1):16–21. doi: 10.15829/1728-8800-2014-1-16-21 EDN: RZDWHZGlazachev OS. Optimization of Clinical Application of Interval Hypoxic Training. Biomedical engineering. 2013;3(279)):21–24. EDN: QBMKPFZagaĭnaia E, Kopylov FIu, Glazachev OS, et al. Effect of interval hypoxic-hypoxic training on exercise tolerance in patients with angina pectoris functional classes II—III on background of optimal medical therapy. Russian Journal of Cardiology and Cardiovascular Surgery. 2015;8(3):33–38. doi: 10.17116/kardio20158333-38 EDN: ULFCORLyamina NP, Lyamina SV, Skorobogatyth NV, Ksenofontova IV, Spirina GK. Controlled hypoxia-hyperoxytherapy as a component of a targeted approach in the rehabilitation of patients with multimorbidity: a single-center, randomized, placebo-controlled, prospective study. Physical and rehabilitation medicine, medical rehabilitation. 2023;5(4):279–288. doi: 10.36425/rehab608182 EDN: YOGGRYTessema B, Sack U, König B, Serebrovska Z, Egorov E. Effects of Intermittent Hypoxia in Training Regimes and in Obstructive Sleep Apnea on Aging Biomarkers and Age-Related Diseases: A Systematic Review. Front Aging Neurosci. 2022;14:878278. doi: 10.3389/fnagi.2022.878278 EDN: BYSJPVSemenza GL. Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu Rev Pathol. 2014;9:47–71. doi: 10.1146/annurev-pathol-012513-104720 EDN: UVKZFNAntikainen H, Driscoll M, Haspel G, Dobrowolski R. TOR-mediated regulation of metabolism in aging. Aging Cell. 2017;16(6):1219–1233. doi: 10.1111/acel.12689Hong S, Zhao B, Lombard DB, Fingar DC, Inoki K. Cross-talk between sirtuin and mammalian target of rapamycin complex 1 (mTORC1) signaling in the regulation of S6 kinase 1 (S6K1) phosphorylation. J Biol Chem. 2014;289(19):13132–13141. doi: 10.1074/jbc.M113.520734 EDN: YEXDXHPan H, Finkel T. Key proteins and pathways that regulate lifespan. J Biol Chem. 2017;292(16):6452–6460. doi: 10.1074/jbc.R116.771915Ruderman NB, Xu XJ, Nelson L, et al. AMPK and SIRT1: a long-standing partnership? Am J Physiol Endocrinol Metab. 2010;298(4):E751–E760. doi: 10.1152/ajpendo.00745.2009Luo Z, Tian M, Yang G, et al. Hypoxia signaling in human health and diseases: implications and prospects for therapeutics. Signal Transduct Target Ther. 2022;7(1):218. doi: 10.1038/s41392-022-01080-1 EDN: WSHTZPUzun AB, Iliescu MG, Stanciu LE, et al. Effectiveness of Intermittent Hypoxia-Hyperoxia Therapy in Different Pathologies with Possible Metabolic Implications. Metabolites. 2023;13(2):181. doi: 10.3390/metabo13020181 EDN: ZWMOJWTobin B, Costalat G, Renshaw GMC. Intermittent not continuous hypoxia provoked haematological adaptations in healthy seniors: hypoxic pattern may hold the key. Eur J Appl Physiol. 2020;120(3):707–718. doi: 10.1007/s00421-020-04310-y EDN: NNYVVSCorrado C, Fontana S. Hypoxia and HIF Signaling: One Axis with Divergent Effects. Int J Mol Sci. 2020;21(16):5611. doi: 10.3390/ijms21165611 EDN: RYHJSZWahl P, Schmidt A, Demarees M, et al. Responses of angiogenic growth factors to exercise, to hypoxia and to exercise under hypoxic conditions. Int J Sports Med. 2013;34(2):95–100. doi: 10.1055/s-0032-1314815Serebrovskaya TV, Xi L. Intermittent hypoxia training as non-pharmacologic therapy for cardiovascular diseases: Practical analysis on methods and equipment. Exp Biol Med (Maywood). 2016;241(15):1708–1723. doi: 10.1177/1535370216657614 EDN: WSYEFBBayer U, Likar R, Pinter G, et al. Intermittent hypoxic-hyperoxic training on cognitive performance in geriatric patients. Alzheimers Dement (N Y). 2017;3(1):114–122. doi: 10.1016/j.trci.2017.01.002 EDN: YVDPHJBowser JL, Lee JW, Yuan X, Eltzschig HK. The hypoxia-adenosine link during inflammation. J Appl Physiol (1985). 2017;123(5):1303–1320. doi: 10.1152/japplphysiol.00101.2017Timon R, Martínez-Guardado I, Camacho-Cardeñosa A, et al. Effect of intermittent hypoxic conditioning on inflammatory biomarkers in older adults. Exp Gerontol. 2021;152:111478. doi: 10.1016/j.exger.2021.111478 EDN: RZAIWQSazontova TG, Bolotova AV, Bedareva IV, Kostina NV, Arkhipenko YV. Adaptation to intermittent hypoxia/hyperoxia enhances efficiency of exercise training. In: Xi L, Serebrovskaya TV, editors. Intermittent hypoxia and human diseases. London: Springer London; 2012. P. 191–205.Bell EL, Klimova TA, Eisenbart J, Schumacker PT, Chandel NS. Mitochondrial reactive oxygen species trigger hypoxia-inducible factor-dependent extension of the replicative life span during hypoxia. Mol Cell Biol. 2007;27(16):5737–5745. doi: 10.1128/MCB.02265-06Chandel NS, Schumacker PT. Cellular oxygen sensing by mitochondria: old questions, new insight. J Appl Physiol (1985). 2000;88(5):1880–1889. doi: 10.1152/jappl.2000.88.5.1880 EDN: LPLUHFLukyanova LD, Kirova YuI. Effect of hypoxic preconditioning on free radical processes in tissues of rats with different resistance to hypoxia. Bulletin of Experimental Biology and Medicine. 2011;151(3):263–268. EDN: NSAHVFSena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012;48(2):158–167. doi: 10.1016/j.molcel.2012.09.025Afina AB, Oleg SG, Alexander AB, et al. The Effects of Intermittent Hypoxic-Hyperoxic Exposures on Lipid Profile and Inflammation in Patients With Metabolic Syndrome. Front Cardiovasc Med. 2021;8:700826. doi: 10.3389/fcvm.2021.700826 EDN: CPYBXPBondarenko NN, Khomutov EV, Ryapolova TL, et al. Molecular and cellular mechanisms of hypoxic response. Ul'yanovskiy mediko-biologicheskiy zhurnal. 2023;2:6–29. doi: 10.34014/2227-1848-2023-2-6-29 EDN: KDWYWVLuo Y, Chen Q, Zou J, et al. Chronic Intermittent Hypoxia Exposure Alternative to Exercise Alleviates High-Fat-Diet-Induced Obesity and Fatty Liver. Int J Mol Sci. 2022;23(9):5209. doi: 10.3390/ijms23095209 EDN: ENIIJYEltzschig HK. Extracellular adenosine signaling in molecular medicine. J Mol Med (Berl). 2013;91(2):141–146. doi: 10.1007/s00109-013-0999-z EDN: HDPXPWEltzschig HK, Weissmüller T, Mager A, Eckle T. Nucleotide metabolism and cell-cell interactions. Methods Mol Biol. 2006;341:73–87. doi: 10.1385/1-59745-113-4Heß V, Kasim M, Mathia S, et al. Episodic Hypoxia Promotes Defence Against Cellular Stress. Cell Physiol Biochem. 2019;52(5):1075–1091. doi: 10.33594/000000073.Lukyanova LD, Germanova EL, Kopaladze RA. Development of resistance of an organism under various conditions of hypoxic preconditioning: role of the hypoxic period and reoxygenation. Bulletin of Experimental Biology and Medicine. 2009;147(4):380–384. EDN: MUEFSZArkhipenko YV, Sazontova TG, Zhukova AG. Adaptation to periodic hypoxia and hyperoxia improves resistance of membrane structures in heart, liver, and brain. Bull Exp Biol Med. 2005;140(3):278–281. doi: 10.1007/s10517-005-0466-0 EDN: LJKTNRTownsend K, Tseng YH. Brown adipose tissue: Recent insights into development, metabolic function and therapeutic potential. Adipocyte. 2012;1(1):13–24. doi: 10.4161/adip.18951Duennwald T, Gatterer H, Groop PH, Burtscher M, Bernardi L. Effects of a single bout of interval hypoxia on cardiorespiratory control and blood glucose in patients with type 2 diabetes. Diabetes Care. 2013;36(8):2183–2189. doi: 10.2337/dc12-2113 EDN: SQDPCZDale EA, Ben Mabrouk F, Mitchell GS. Unexpected benefits of intermittent hypoxia: enhanced respiratory and nonrespiratory motor function. Physiology (Bethesda). 2014;29(1):39–48. doi: 10.1152/physiol.00012.2013 EDN: YEIKNFGlazachev OS, Dudnik EN, Pozdnyakov YuM. Adaptation to intermittent hypoxia-hyperoxia in rehabilitation of patients with coronary artery disease. Humans and their health. 2014;(1):58–64. EDN: SNMMHRBehrendt T, Bielitzki R, Behrens M, Herold F, Schega L. Effects of Intermittent Hypoxia-Hyperoxia on Performance- and Health-Related Outcomes in Humans: A Systematic Review. Sports Med Open. 2022;8(1):70. doi: 10.1186/s40798-022-00450-x EDN: KPLFZVIgnatenko GA, Mukhi IV, Gavrilyak VG. Hypoxia hyperoxitherapy in the treatment of patients with comorbid cardiac pathology. Universiti Clinic. 2019;(1(30)):5–10. EDN: EZEUZZGlazachev OS, Dudnik EN, Platonenko AV, Spirina GK. Gipoksicheskie trenirovki v kardioreabilitatsii: korrektsiya metabolicheskikh i kardiovaskulyarnykh faktorov riska. CardioSomatics. 2011;2(1-1):23–24. doi: 10.26442/CS45113 EDN: TRKQURKryzhanovskaya SYu, Dudnik EN, Zapara MA, Samarzeva VG, Glazachev OS. Hypoxic conditioning procedures do not lead to excessive activation of oxidative stress in healthy subjects. Russian journal of physiology. 2019;105(1):89–99. doi: 10.1134/S0869813919010047 EDN: VUBUFJGlazachev OS, Kryzhanovskaya SYu, Zapara MA, et al. Safety and Efficacy of Intermittent Hypoxia Conditioning as a New Rehabilitation/Secondary Prevention Strategy for Patients with CardiovascularDiseases: A Systematic Review and Meta-analysis. Current Cardiology Reviews. 2021;17(6):e051121193317. doi: 10.2174/1573403X17666210514005235 EDN: CMJNPISchega L, Peter B, Brigadski T, et al. Effect of intermittent normobaric hypoxia on aerobic capacity and cognitive function in older people. J Sci Med Sport. 2016;19(11):941–945. doi: 10.1016/j.jsams.2016.02.012 EDN: XTFEWLBehrendt T, Bielitzki R, Behrens M, Glazachev OS, Schega L. Effects of Intermittent Hypoxia-Hyperoxia Exposure Prior to Aerobic Cycling Exercise on Physical and Cognitive Performance in Geriatric Patients-A Randomized Controlled Trial. Front Physiol. 202226;13:899096. doi: 10.3389/fphys.2022.899096 EDN: SZSRZNvan Hulten V, van Meijel RLJ, Goossens GH. The impact of hypoxia exposure on glucose homeostasis in metabolically compromised humans: A systematic review. Rev Endocr Metab Disord. 2021;22(2):471–483. doi: 10.1007/s11154-021-09654-0 EDN: FOIAMHBurtscher J, Maglione V, Di Pardo A, et al. A Rationale for Hypoxic and Chemical Conditioning in Huntington's Disease. Int J Mol Sci. 2021;22(2):582. doi: 10.3390/ijms22020582Burtscher J, Syed MMK, Lashuel HA, Millet GP. Hypoxia Conditioning as a Promising Therapeutic Target in Parkinson's Disease? Mov Disord. 2021;36(4):857–861. doi: 10.1002/mds.28544 EDN: ARNRILBurtscher J, Mallet RT, Burtscher M, Millet GP. Hypoxia and brain aging: Neurodegeneration or neuroprotection? Ageing Res Rev. 2021;68:101343. doi: 10.1016/j.arr.2021.101343 EDN: NVFFAPCamacho-Cardenosa A, Camacho-Cardenosa M, Brooks D, et al. Effects training in hypoxia on cardiometabolic parameters in obese people: A systematic review of randomized controlled trial. Aten Primaria. 2019;51(7):397–405. doi: 10.1016/j.aprim.2018.03.011Saeed O, Bhatia V, Formica P, et al. Improved exercise performance and skeletal muscle strength after simulated altitude exposure: a novel approach for patients with chronic heart failure. J Card Fail. 2012;18(5):387–391. doi: 10.1016/j.cardfail.2012.02.003Lyamina NP, Lyamina SV, Senchiknin VN, et al. Normobaric hypoxia conditioning reduces blood pressure and normalizes nitric oxide synthesis in patients with arterial hypertension. J Hypertens. 2011;29(11):2265–2272. doi: 10.1097/HJH.0b013e32834b5846. EDN: PECQPRIgnatenko GA, Mukhin IV, Gavrilyak VG, Chebotareva EN, Dzyuban AS. Ischemic preconditioning and the potential of hypoxia-hyperoxytherapy. Vestnik neotlozhnoi i vosstanovitel'noi khirurgii. 2018;3(3):249–255. EDN: PHMRBWSerebrovska TV, Portnychenko AG, Portnichenko VI, et al. Effects of intermittent hypoxia training on leukocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and blood insulin level in prediabetes patients. Eur J Appl Physiol. 2019;119(3):813–823. doi: 10.1007/s00421-019-04072-2 EDN: WYTUSVFuller NR, Courtney R. A case of remission from pre-diabetes following intermittent hypoxic training. Obes Res Clin Pract. 2016;10(4):487–491. doi: 10.1016/j.orcp.2016.05.008 EDN: XZHEMXBrinkmann C, Metten A, Scriba P, et al. Hypoxia and Hyperoxia Affect Serum Angiogenic Regulators in T2DM Men during Cycling. Int J Sports Med. 2017;38(2):92–98. doi: 10.1055/s-0042-116823 EDN: YCUGLJ