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Kapel JS, Stokholm R, Elmengaard B, Nochi Z, Olsen RJ, Foldager CB. Individualized Algorithm-Based Intermittent Hypoxia Improves Quality of Life in Patients Suffering from Long-Term Sequelae After COVID-19 Infection. J Clin Med 2025; 14:1590. [PMID: 40095507 PMCID: PMC11900126 DOI: 10.3390/jcm14051590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2025] [Revised: 02/17/2025] [Accepted: 02/21/2025] [Indexed: 03/19/2025] Open
Abstract
Background/Objectives: Post-COVID-19 condition (PCC), also known as long COVID, has emerged as a recognized syndrome affecting millions of people worldwide, significantly impairing their quality of life. Currently, no effective therapeutic options are available to manage this condition. The objective of the present study was to evaluate the long-term effects of personalized, algorithm-based intermittent hypoxia-hyperoxia conditioning (IHHC) on quality of life and pain in patients with PCC. Methods: This open-label cohort study included 199 PCC patients, aged 11-87 years (female-to-male ratio: 67:33) and experiencing moderate-to-severe fatigue, between 1 January 2020 and 31 December 2023. Each patient received an algorithm-based treatment plan tailored to their demographics, symptom duration, and baseline pain (NRS) and quality of life (SF-36) scores. Patients received an average of six treatment sessions (range: 2-21), each consisting of intermittent hypoxic-hyperoxic cycles, with hypoxia (9-13% O2) lasting 3-8 min and hyperoxia (34-36% O2) lasting 1-3 min. The primary outcomes were changes in the NRS and SF-36 scores at the 6-week and 6-month follow-ups. Results: At the 6-week follow-up after treatment initiation, the SF-36 scores increased by 102 points (p < 0.001, 95% CI: 78.4-127), and this improvement persisted at the 6-month follow-up (Δ106, p < 0.001, 95% CI: 57.0-154). Pain was reduced by 28-32% at both follow-up time points, exceeding the clinically relevant threshold. Health transition scores indicated a patient-perceived improvement in health status. Conclusions: In this study, a personalized, algorithm-based IHHC alleviated pain and improved quality of life in patients suffering from persistent long-term sequelae after COVID-19 infection. The effects were sustained for up to six months. Further research is warranted to elucidate the mechanisms underlying IHHC's therapeutic effects in this patient population.
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Affiliation(s)
| | | | | | - Zahra Nochi
- Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, 8200 Aarhus N, Denmark
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, 8200 Aarhus N, Denmark
| | - Rikke Jentoft Olsen
- Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and Aarhus University Hospital, 8200 Aarhus N, Denmark
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Panza GS, Soltesz AE, Zhao F, Fritz NE, Delgado AD, Sutor TW. Intermittent hypoxia and motor learning: new information and new questions. J Physiol 2025; 603:595-597. [PMID: 39470714 DOI: 10.1113/jp287594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/30/2024] Open
Affiliation(s)
- Gino S Panza
- Department of Health Care Sciences, Program of Occupational Therapy, Wayne State University, Detroit, MI, USA
- Translational Neuroscience Program, Wayne State University School of Medicine, Detroit, MI, USA
- John D. Dingell Veterans Affairs Medical Center, Detroit, MI, USA
| | - Alexandra E Soltesz
- Translational Neuroscience Program, Wayne State University School of Medicine, Detroit, MI, USA
- John D. Dingell Veterans Affairs Medical Center, Detroit, MI, USA
| | - Fei Zhao
- Department of Health Care Sciences, Program of Occupational Therapy, Wayne State University, Detroit, MI, USA
- John D. Dingell Veterans Affairs Medical Center, Detroit, MI, USA
| | - Nora E Fritz
- Translational Neuroscience Program, Wayne State University School of Medicine, Detroit, MI, USA
- Department of Health Care Sciences, Program of Physical Therapy, Wayne State University, Detroit, MI, USA
- Department of Neurology, Wayne State University, Detroit, MI, USA
| | - Andrew D Delgado
- Department of Population Health Science & Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Tommy W Sutor
- Center for Breathing Research and Therapeutics and Department of Physical Therapy, University of Florida, Gainesville, FL, USA
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Doehner W, Fischer A, Alimi B, Muhar J, Springer J, Altmann C, Schueller P. Intermittent Hypoxic-Hyperoxic Training During Inpatient Rehabilitation Improves Exercise Capacity and Functional Outcome in Patients With Long Covid: Results of a Controlled Clinical Pilot Trial. J Cachexia Sarcopenia Muscle 2024; 15:2781-2791. [PMID: 39559920 PMCID: PMC11634465 DOI: 10.1002/jcsm.13628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Accepted: 09/23/2024] [Indexed: 11/20/2024] Open
Abstract
INTRODUCTION Long COVID-19 illness is a severely disabling disease with shortness of breath, weakness and fatigue as leading symptoms, resulting in poor quality of life and substantial delay in return to work. No specific respiratory therapy has been validated for patients with long COVID. The intermittent hypoxia-hyperoxia training (IHHT) is a respiratory therapeutic modality to improve exercise performance via controlled respiratory conditioning. The purpose of the present study is to investigate the therapeutic effect of IHHT on functional and symptomatic recovery of patients with long COVID syndrome. METHODS A prospective, controlled, open-treatment interventional study was conducted in patients with long COVID who were admitted to an inpatient rehabilitation programme. Patients were assigned nonrandomized to receive IHHT in addition to the standardized rehabilitation programme (IHHT group) or standard rehabilitation alone (control group). The IHHT group received supervised sessions of intermittent hypoxic (10-12% O2) and hyperoxic (30-35% O2) breathing three times per week throughout the rehabilitation period. Primary endpoint was improved walking distance in a 6-min walk test (6MWT) between study groups. Secondary endpoints were change in stair climbing power, dyspnoea (Borg dyspnoea Scale), fatigue assessment scale (FAS) and change in health-related quality of life (HRQoL) assessed by patient global assessment (PGA), EQ-5D analogue scale and the MEDIAN Corona Recovery Score (MCRS). Further assessments included maximum handgrip strength, nine hole peg test, timed up-and-go, respiratory function and functional ambulation category (FAC), serum analyses and safety of the intervention. RESULTS A total of 145 patients were included in the study (74% female, mean age 53 ± 12 years) and assigned to IHHT (n = 70) or standard care (n = 75). The 6MWT distance improved 2.8-fold in the IHHT group compared to the control group (91.7 ± 50.1 m vs. 32.6 ± 54.2 m, ANCOVA p < 0.001). Stair climbing power improved 3.7-fold in the IHHT group compared to controls (-1.91 ± 2.23 s vs. -0.51 ± 1.93 s, p < 0.001). Secondary endpoints on dyspnoea, fatigue and HRQoL (PGA, EQ-5D and MCRS) improved significantly in the IHHT group compared to controls. The IHHT group exhibited a significant decrease in blood pressure, heart rate and increase in haemoglobin levels that was not observed in the control group. No adverse events were observed. CONCLUSION Respiratory treatment with IHHT in addition to a multidisciplinary rehabilitation programme improves functional capacity, symptomatic status and quality of life in patients with disabling long COVID. IHHT has been demonstrated to be safe, well tolerated and feasible to be integrated in an inpatient rehabilitation programme to improve outcome in long COVID.
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Affiliation(s)
- Wolfram Doehner
- Berlin Institute of Health Center for Regenerative TherapiesCharité ‐ Universitätsmedizin BerlinBerlinGermany
- German Heart Center of the Charite, Department of Cardiology, Campus Virchow, German Centre for Cardiovascular Research (DZHK), partner site BerlinCharité ‐ Universitätsmedizin BerlinBerlinGermany
- Center for Stroke Research Berlin (CSB)Charité Universitätsmedizin BerlinBerlinGermany
| | - Azadeh Fischer
- Berlin Institute of Health Center for Regenerative TherapiesCharité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Banafsheh Alimi
- Klinik für Kardiologie und PneumologieMedian Klinikum FlechtingenFlechtingenGermany
| | - Jasmin Muhar
- Klinik für Kardiologie und PneumologieMedian Klinikum FlechtingenFlechtingenGermany
| | - Jochen Springer
- Berlin Institute of Health Center for Regenerative TherapiesCharité ‐ Universitätsmedizin BerlinBerlinGermany
| | - Christoph Altmann
- MVZ Cardiologicum Dresden und PirnaStudienzentrum DresdenDresdenGermany
| | - Per Otto Schueller
- Klinik für Kardiologie und PneumologieMedian Klinikum FlechtingenFlechtingenGermany
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Shepherd AI, James TJ, Gould AAM, Mayes H, Neal R, Shute J, Tipton MJ, Massey H, Saynor ZL, Perissiou M, Montgomery H, Sturgess C, Makaronidis J, Murray AJ, Grocott MPW, Cummings M, Young-Min S, Rennell-Smyth J, McNarry MA, Mackintosh KA, Dent H, Robson SC, Corbett J. Impact of nocturnal hypoxia on glycaemic control, appetite, gut microbiota and inflammation in adults with type 2 diabetes mellitus: A single-blind cross-over trial. J Physiol 2024; 602:5835-5854. [PMID: 38769692 DOI: 10.1113/jp285322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 04/22/2024] [Indexed: 05/22/2024] Open
Abstract
High altitude residents have a lower incidence of type 2 diabetes mellitus (T2DM). Therefore, we examined the effect of repeated overnight normobaric hypoxic exposure on glycaemic control, appetite, gut microbiota and inflammation in adults with T2DM. Thirteen adults with T2DM [glycated haemoglobin (HbA1c): 61.1 ± 14.1 mmol mol-1; aged 64.2 ± 9.4 years; four female] completed a single-blind, randomised, sham-controlled, cross-over study for 10 nights, sleeping when exposed to hypoxia (fractional inspired O2 [F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ ] = 0.155; ∼2500 m simulated altitude) or normoxic conditions (F I O 2 ${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ = 0.209) in a randomised order. Outcome measures included: fasted plasma [glucose]; [hypoxia inducible factor-1α]; [interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]; [heat shock protein 70]; [butyric acid]; peak plasma [glucose] and insulin sensitivity following a 2 h oral glucose tolerance test; body composition; appetite indices ([leptin], [acyl ghrelin], [peptide YY], [glucagon-like peptide-1]); and gut microbiota diversity and abundance [16S rRNA amplicon sequencing]. During intervention periods, accelerometers measured physical activity, sleep duration and efficiency, whereas continuous glucose monitors were used to assess estimated HbA1c and glucose management indicator and time in target range. Overnight hypoxia was not associated with changes in any outcome measure (P > 0.05 with small effect sizes) except fasting insulin sensitivity and gut microbiota alpha diversity, which exhibited trends (P = 0.10; P = 0.08 respectively) for a medium beneficial effect (d = 0.49; d = 0.59 respectively). Ten nights of overnight moderate hypoxic exposure did not significantly affect glycaemic control, gut microbiome, appetite, or inflammation in adults with T2DM. However, the intervention was well tolerated and a medium effect-size for improved insulin sensitivity and reduced alpha diversity warrants further investigation. KEY POINTS: Living at altitude lowers the incidence of type 2 diabetes mellitus (T2DM). Animal studies suggest that exposure to hypoxia may lead to weight loss and suppressed appetite. In a single-blind, randomised sham-controlled, cross-over trial, we assessed the effects of 10 nights of hypoxia (fractional inspired O2 ∼0.155) on glucose homeostasis, appetite, gut microbiota, inflammatory stress ([interleukin-6]; [tumour necrosis factor-α]; [interleukin-10]) and hypoxic stress ([hypoxia inducible factor 1α]; heat shock protein 70]) in 13 adults with T2DM. Appetite and inflammatory markers were unchanged following hypoxic exposure, but an increased insulin sensitivity and reduced gut microbiota alpha diversity were associated with a medium effect-size and statistical trends, which warrant further investigation using a definitive large randomised controlled trial. Hypoxic exposure may represent a viable therapeutic intervention in people with T2DM and particularly those unable or unwilling to exercise because barriers to uptake and adherence may be lower than for other lifestyle interventions (e.g. diet and exercise).
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Affiliation(s)
- Anthony I Shepherd
- Extreme Environments Laboratory, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
- Clinical Health and Rehabilitation Team, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
- Diabetes and Endocrinology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Thomas J James
- Extreme Environments Laboratory, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
- Clinical Health and Rehabilitation Team, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Alex A M Gould
- Extreme Environments Laboratory, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Harry Mayes
- Extreme Environments Laboratory, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Rebecca Neal
- Department of Rehabilitation and Sport Sciences, Bournemouth University, Poole, UK
| | - Janis Shute
- School of Pharmacy and Biomedical Sciences, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Michael J Tipton
- Extreme Environments Laboratory, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Heather Massey
- Extreme Environments Laboratory, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Zoe L Saynor
- Clinical Health and Rehabilitation Team, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Maria Perissiou
- Clinical Health and Rehabilitation Team, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Hugh Montgomery
- Centre for Human Health and Performance, Dept Medicine, University College London, London, UK
| | - Connie Sturgess
- Centre for Human Health and Performance, Dept Medicine, University College London, London, UK
| | - Janine Makaronidis
- Centre for Obesity Research, University College London, London, UK
- National Institute for Health and Care Research, University College London Hospitals Biomedical Research Centre, London, UK
| | - Andrew J Murray
- Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK
| | - Michael P W Grocott
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton & University of Southampton, Southampton, UK
| | - Michael Cummings
- Diabetes and Endocrinology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Steven Young-Min
- Rheumatology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Janet Rennell-Smyth
- Clinical Health and Rehabilitation Team, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
- Patient and public involvement member
| | - Melitta A McNarry
- School of Biological Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Kelly A Mackintosh
- School of Biological Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Hannah Dent
- School of Pharmacy and Biomedical Sciences, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
- Institute of Life Sciences and Healthcare, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Samuel C Robson
- School of Pharmacy and Biomedical Sciences, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
- Applied Sports, Technology, Exercise and Medicine (A-STEM) Research Centre, School of Sport and Exercise Sciences, Swansea University, Swansea, UK
- Institute of Life Sciences and Healthcare, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
| | - Jo Corbett
- Extreme Environments Laboratory, School of Sport, Health and Exercise Science, Faculty of Science and Health, University of Portsmouth, Portsmouth, UK
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Burtscher J, Citherlet T, Camacho-Cardenosa A, Camacho-Cardenosa M, Raberin A, Krumm B, Hohenauer E, Egg M, Lichtblau M, Müller J, Rybnikova EA, Gatterer H, Debevec T, Baillieul S, Manferdelli G, Behrendt T, Schega L, Ehrenreich H, Millet GP, Gassmann M, Schwarzer C, Glazachev O, Girard O, Lalande S, Hamlin M, Samaja M, Hüfner K, Burtscher M, Panza G, Mallet RT. Mechanisms underlying the health benefits of intermittent hypoxia conditioning. J Physiol 2024; 602:5757-5783. [PMID: 37860950 DOI: 10.1113/jp285230] [Citation(s) in RCA: 30] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Accepted: 10/11/2023] [Indexed: 10/21/2023] Open
Abstract
Intermittent hypoxia (IH) is commonly associated with pathological conditions, particularly obstructive sleep apnoea. However, IH is also increasingly used to enhance health and performance and is emerging as a potent non-pharmacological intervention against numerous diseases. Whether IH is detrimental or beneficial for health is largely determined by the intensity, duration, number and frequency of the hypoxic exposures and by the specific responses they engender. Adaptive responses to hypoxia protect from future hypoxic or ischaemic insults, improve cellular resilience and functions, and boost mental and physical performance. The cellular and systemic mechanisms producing these benefits are highly complex, and the failure of different components can shift long-term adaptation to maladaptation and the development of pathologies. Rather than discussing in detail the well-characterized individual responses and adaptations to IH, we here aim to summarize and integrate hypoxia-activated mechanisms into a holistic picture of the body's adaptive responses to hypoxia and specifically IH, and demonstrate how these mechanisms might be mobilized for their health benefits while minimizing the risks of hypoxia exposure.
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Affiliation(s)
- Johannes Burtscher
- Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Tom Citherlet
- Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Alba Camacho-Cardenosa
- Department of Physical Education and Sports, Faculty of Sports Science, Sport and Health University Research Institute (iMUDS), University of Granada, Granada, Spain
| | - Marta Camacho-Cardenosa
- Clinical Management Unit of Endocrinology and Nutrition - GC17, Maimónides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofía University Hospital, Córdoba, Spain
| | - Antoine Raberin
- Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Bastien Krumm
- Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Erich Hohenauer
- Rehabilitation and Exercise Science Laboratory (RES lab), Department of Business Economics, Health and Social Care, University of Applied Sciences and Arts of Southern Switzerland, Landquart, Switzerland
- International University of Applied Sciences THIM, Landquart, Switzerland
- Department of Neurosciences and Movement Science, University of Fribourg, Fribourg, Switzerland
| | - Margit Egg
- Institute of Zoology, University of Innsbruck, Innsbruck, Austria
| | - Mona Lichtblau
- Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Julian Müller
- Department of Pulmonology, University Hospital Zurich, Zurich, Switzerland
- University of Zurich, Zurich, Switzerland
| | - Elena A Rybnikova
- Pavlov Institute of Physiology, Russian Academy of Sciences, St Petersburg, Russia
| | - Hannes Gatterer
- Institute of Mountain Emergency Medicine, Eurac Research, Bolzano, Italy
- Institute for Sports Medicine, Alpine Medicine and Health Tourism (ISAG), UMIT TIROL-Private University for Health Sciences and Health Technology, Hall in Tirol, Austria
| | - Tadej Debevec
- Faculty of Sport, University of Ljubljana, Ljubljana, Slovenia
- Department of Automatics, Biocybernetics and Robotics, Jožef Stefan Institute, Ljubljana, Slovenia
| | - Sebastien Baillieul
- Service Universitaire de Pneumologie Physiologie, University of Grenoble Alpes, Inserm, Grenoble, France
| | | | - Tom Behrendt
- Chair Health and Physical Activity, Department of Sport Science, Institute III, Otto von Guericke University Magdeburg, Magdeburg, Germany
| | - Lutz Schega
- Chair Health and Physical Activity, Department of Sport Science, Institute III, Otto von Guericke University Magdeburg, Magdeburg, Germany
| | - Hannelore Ehrenreich
- Clinical Neuroscience, University Medical Center and Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany
| | - Grégoire P Millet
- Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Max Gassmann
- Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Zurich, Switzerland
- Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland
- Universidad Peruana Cayetano Heredia (UPCH), Lima, Peru
| | - Christoph Schwarzer
- Institute of Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
| | - Oleg Glazachev
- Department of Normal Physiology, N.V. Sklifosovsky Institute of Clinical Medicine, I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - Olivier Girard
- School of Human Sciences (Exercise and Sport Science), The University of Western Australia, Crawley, Western Australia, Australia
| | - Sophie Lalande
- Department of Kinesiology and Health Education, University of Texas at Austin, Austin, TX, USA
| | - Michael Hamlin
- Department of Tourism, Sport and Society, Lincoln University, Christchurch, New Zealand
| | - Michele Samaja
- Department of Health Science, University of Milan, Milan, Italy
| | - Katharina Hüfner
- Department of Psychiatry, Psychotherapy, Psychosomatics and Medical Psychology, University Hospital for Psychiatry II, Medical University of Innsbruck, Innsbruck, Austria
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
| | - Gino Panza
- The Department of Health Care Sciences, Program of Occupational Therapy, Wayne State University, Detroit, MI, USA
- John D. Dingell VA Medical Center Detroit, Detroit, MI, USA
| | - Robert T Mallet
- Department of Physiology & Anatomy, University of North Texas Health Science Center, Fort Worth, TX, USA
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Xinliang Z, Achkasov EE, Gavrikov LK, Yuchen L, Zhang C, Dudnik EN, Rumyantseva O, Beeraka NM, Glazachev OS. Assessing the importance and safety of hypoxia conditioning for patients with occupational pulmonary diseases: A recent clinical perspective. Biomed Pharmacother 2024; 178:117275. [PMID: 39126774 DOI: 10.1016/j.biopha.2024.117275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 07/25/2024] [Accepted: 08/05/2024] [Indexed: 08/12/2024] Open
Abstract
Occupational pulmonary diseases (OPDs) pose a significant global health challenge, contributing to high mortality rates. This review delves into the pathophysiology of hypoxia and the safety of intermittent hypoxic conditioning (IHC) in OPD patients. By examining sources such as PubMed, Relemed, NLM, Scopus, and Google Scholar, the review evaluates the efficacy of IHC in clinical outcomes for OPD patients. It highlights the complexities of cardiovascular and respiratory regulation dysfunctions in OPDs, focusing on respiratory control abnormalities and the impact of intermittent hypoxic exposures. Key areas include the physiological effects of hypoxia, the role of hypoxia-inducible factor-1 alpha (HIF-1α) in occupational lung diseases, and the links between brain ischemia, stroke, and OPDs. The review also explores the interaction between intermittent hypoxic exposures, mitochondrial energetics, and lung physiology. The potential of IHE to improve clinical manifestations and underlying pathophysiology in OPD patients is thoroughly examined. This comprehensive analysis aims to benefit molecular pathologists, pulmonologists, clinicians, and physicians by enhancing understanding of IHE's clinical benefits, from research to patient care, and improving clinical outcomes for OPD patients.
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Affiliation(s)
- Zhang Xinliang
- Chair of Sports Medicine and Rehabilitation, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Str., Moscow 119991, Russia; Co-Chair of Normal Physiology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Str., Moscow 119991, Russia.
| | - Eugeny E Achkasov
- Chair of Sports Medicine and Rehabilitation, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Str., Moscow 119991, Russia.
| | - Leonid K Gavrikov
- Volgograd State Medical University, 1, Pavshikh Bortsov Sq., Volgograd 400131, Russia.
| | - Li Yuchen
- Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Str., Moscow 119991, Russia.
| | - Chen Zhang
- Chair of Epidemiology and Modern Technologies of Vaccination, Institute of Professional Education, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Str., Moscow 119991, Russia
| | - Elena N Dudnik
- Co-Chair of Normal Physiology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Str., Moscow 119991, Russia.
| | - Olga Rumyantseva
- Izmerov Research Institute of Occupational Health, 31 Budeynniy Avenye, Moscow 105275, Russia.
| | - Narasimha M Beeraka
- Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut Street, R4-168, Indianapolis, IN 46202, USA; Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str., Moscow 119991, Russia; Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Chiyyedu, Anantapuramu, Andhra Pradesh 515721, India.
| | - Oleg S Glazachev
- Co-Chair of Normal Physiology, Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Str., Moscow 119991, Russia.
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7
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Duderstadt Y, Schreiber S, Burtscher J, Schega L, Müller NG, Brigadski T, Braun-Dullaeus RC, Leßmann V, Müller P. Controlled Hypoxia Acutely Prevents Physical Inactivity-Induced Peripheral BDNF Decline. Int J Mol Sci 2024; 25:7536. [PMID: 39062779 PMCID: PMC11276956 DOI: 10.3390/ijms25147536] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 06/30/2024] [Accepted: 07/04/2024] [Indexed: 07/28/2024] Open
Abstract
Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. A total of 25 healthy adults (25.8 ± 3.3 years, 15 female) were analyzed in a randomized controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO2] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO2 were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. NH decreased SpO2 (p < 0.001, ηp2 = 0.747) and increased heart rate (p = 0.006, ηp2 = 0.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p < 0.001, ηp2 = 0.581) and plasma (p < 0.001, ηp2 = 0.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p = 0.018) in serum and after 30 min (p = 0.040) and 90 min (p = 0.005) in plasma. There was no significant BDNF decline under NH. A 24 h follow-up examination showed a significant decline in serum BDNF, both after NH and NOR. Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.
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Affiliation(s)
- Yves Duderstadt
- Division of Cardiology and Angiology, University Hospital Magdeburg, 39120 Magdeburg, Germany; (Y.D.)
- German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany
- Department of Sports Science, Chair of Health and Physical Activity, Otto-von-Guericke University, 39104 Magdeburg, Germany
| | - Stefanie Schreiber
- German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany
- Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), 39120 Magdeburg, Germany
- Division of Neurology, University Hospital Magdeburg, 39120 Magdeburg, Germany
- Center for Behavioral Brain Sciences (CBBS), 39120 Magdeburg, Germany
- German Center for Mental Health (DZPG), 39120 Magdeburg, Germany
| | - Johannes Burtscher
- Institute of Sports Science, University Innsbruck, 6020 Innsbruck, Austria;
| | - Lutz Schega
- Department of Sports Science, Chair of Health and Physical Activity, Otto-von-Guericke University, 39104 Magdeburg, Germany
| | - Notger G. Müller
- German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany
- Faculty of Health Sciences Brandenburg, University of Potsdam, 14476 Potsdam, Germany
| | - Tanja Brigadski
- Institute of Physiology, Otto-von-Guericke University, 39120 Magdeburg, Germany
- Department of Informatics and Microsystems Technology, University of Applied Sciences, 67659 Kaiserslautern, Germany
| | - Rüdiger C. Braun-Dullaeus
- Division of Cardiology and Angiology, University Hospital Magdeburg, 39120 Magdeburg, Germany; (Y.D.)
| | - Volkmar Leßmann
- Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), 39120 Magdeburg, Germany
- Center for Behavioral Brain Sciences (CBBS), 39120 Magdeburg, Germany
- German Center for Mental Health (DZPG), 39120 Magdeburg, Germany
- Institute of Physiology, Otto-von-Guericke University, 39120 Magdeburg, Germany
| | - Patrick Müller
- Division of Cardiology and Angiology, University Hospital Magdeburg, 39120 Magdeburg, Germany; (Y.D.)
- German Center for Neurodegenerative Diseases (DZNE), 39120 Magdeburg, Germany
- Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), 39120 Magdeburg, Germany
- German Center for Mental Health (DZPG), 39120 Magdeburg, Germany
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8
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Zhao Y, Li C, Zhou S, He Y, Wang Y, Zhang Y, Wen L. Enhanced glucose utilization of skeletal muscle after 4 weeks of intermittent hypoxia in a mouse model of type 2 diabetes. PLoS One 2024; 19:e0296815. [PMID: 38271325 PMCID: PMC10810429 DOI: 10.1371/journal.pone.0296815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 12/19/2023] [Indexed: 01/27/2024] Open
Abstract
BACKGROUND Intermittent hypoxia intervention (IHI) has been shown to reduces blood glucose and improves insulin resistance in type 2 diabetes (T2D) and has been suggested as a complementary or alternative intervention to exercise for individuals with limited mobility. Previous research on IHI has assessed cellular glucose uptake rather than utilization. The purpose of this study was to determine the effect of a 4-week IHI, with or without an aerobic exercise, on skeletal muscle glucose utilization as indicated by the changes in pyruvate, lactate, NAD+, and NADH, using a mouse model of diet-induced T2D. In addition, the effects of one exposure to hypoxia (acute) and of a 4-week IHI (chronic) were compared to explore their relationship. METHODS C57BL/6J mice were randomly assigned to normal control and high-fat-diet groups, and the mice that developed diet-induced diabetes were assigned to diabetes control, and intervention groups with 1 hour (acute) or 4 weeks (1 hour/day, 6 days/week) exposure to a hypoxic envrionment (0.15 FiO2), exercise (treadmill run) in normoxia, and exercise in hypoxia, respectively, with N = 7 in each group. The effects of the interventions on concentrations of fasting blood glucose, muscle glucose, GLUT4, lactate, pyruvate, nicotinamide adenine dinucleotide (NAD+), and NADH were measured, and statistically compared between the groups. RESULTS Compared with diabetes control group, the mice treated in the hypoxic environment for 4 weeks showed a significantly higher pyruvate levels and lower lactate/pyruvate ratios in the quadriceps muscle, and the mice exposed to hypoxia without or with aerobic exercise for either for 4 weeks or just 1 hour showed higher NAD+ levels and lower NADH/NAD+ ratios. CONCLUSIONS Exposure to moderate hypoxia for either one bout or 4 weeks significantly increased the body's mitochondrial NAD cyclethe in diabetic mice even in the absence of aerobic exercise. The hypoxia and exercise interventions exhibited synergistic effects on glycolysis. These findings provide mechanistic insights into the effects of IHI in respect of the management of hyperglycemia.
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Affiliation(s)
- Yuqi Zhao
- School of Social Sports and Health Sciences, Tianjin University of Sport, Tianjin, China
- School of Exercise and Health, Nanjing Sport Institute, Nanjing, Jiangsu, China
| | - Chaoqun Li
- School of Kinesiology, Shanghai University of Sport, Shanghai, China
| | - Shi Zhou
- Faculty of Health, Southern Cross University, Lismore, Australia
| | - Youyu He
- School of Social Sports and Health Sciences, Tianjin University of Sport, Tianjin, China
| | - Yun Wang
- Faculty of Health, Southern Cross University, Lismore, Australia
| | - Yuan Zhang
- Faculty of Health, Southern Cross University, Lismore, Australia
| | - Li Wen
- School of Social Sports and Health Sciences, Tianjin University of Sport, Tianjin, China
- School of Exercise and Health, Nanjing Sport Institute, Nanjing, Jiangsu, China
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9
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Boulares A, Pichon A, Faucher C, Bragazzi NL, Dupuy O. Effects of Intermittent Hypoxia Protocols on Cognitive Performance and Brain Health in Older Adults Across Cognitive States: A Systematic Literature Review. J Alzheimers Dis 2024; 101:13-30. [PMID: 39093075 DOI: 10.3233/jad-240711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
Background The rise in the aging population highlights the need to address cognitive decline and neurodegenerative diseases. Intermittent hypoxia (IH) protocols show promise in enhancing cognitive abilities and brain health. Objective This review evaluates IH protocols' benefits on cognition and brain health in older adults, regardless of cognitive status. Methods A systematic search following PRISMA guidelines was conducted across four databases (PubMed, Scopus, Web of Science, and Cochrane Library) and two registers, covering records from inception to May 2024 (PROSPERO: CRD42023462177). Inclusion criteria were: 1) original research with quantitative details; 2) studies involving older adults, with or without cognitive impairment; 3) studies including IH protocols; 4) articles analyzing cognition and brain health in older adults. Results Seven studies and five registered trials met the criteria. Findings indicate that Intermittent Hypoxia Training (IHT) and Intermittent Hypoxia-Hyperoxia Training (IHHT) improved cognitive functions and brain health. Intermittent Hypoxic Exposure (IHE) improved cerebral tissue oxygen saturation, middle cerebral arterial flow velocity, and cerebral vascular conductance, particularly in cognitively impaired populations. IHT and IHHT had no significant effect on BDNF levels. There is a lack of studies on IHHE in older adults with and without cognitive impairment. Conclusions IH protocols may benefit cognition regardless of cognitive status. IHT and IHE positively affect cerebral outcomes, with all protocols having limited effects on BDNF levels. Future research should standardize IH protocols, investigate long-term cognitive effects, and explore neuroprotective biomarkers. Combining these protocols with physical exercise across diverse populations could refine interventions and guide targeted therapeutic strategies.
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Affiliation(s)
- Ayoub Boulares
- Laboratory Mobility, Aging & Exercise-ER20296 (MOVE), Faculty of Sport Sciences-STAPS, University of Poitiers, Poitiers, France
| | - Aurélien Pichon
- Laboratory Mobility, Aging & Exercise-ER20296 (MOVE), Faculty of Sport Sciences-STAPS, University of Poitiers, Poitiers, France
| | - Corentin Faucher
- Laboratory Mobility, Aging & Exercise-ER20296 (MOVE), Faculty of Sport Sciences-STAPS, University of Poitiers, Poitiers, France
| | - Nicola Luigi Bragazzi
- Department of Mathematics and Statistics, Laboratory for Industrial and Applied Mathematics (LIAM), York University, Toronto, ON, Canada
- Department of Food and Drugs, Medical School, Human Nutrition Unit (HNU), University of Parma, Parma, Italy
- United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair, Health Anthropology Biosphere and Healing Systems, University of Genoa, Genoa, Italy
- Department of Health Sciences (DISSAL), Postgraduate School of Public Health, University of Genoa, Genoa, Italy
| | - Olivier Dupuy
- Laboratory Mobility, Aging & Exercise-ER20296 (MOVE), Faculty of Sport Sciences-STAPS, University of Poitiers, Poitiers, France
- School of Kinesiology and Physical Activity Sciences (EKSAP), Faculty of Medicine, University of Montreal, Montreal, QC, Canada
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10
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Panza GS, Burtscher J, Zhao F. Intermittent hypoxia: a call for harmonization in terminology. J Appl Physiol (1985) 2023; 135:886-890. [PMID: 37560767 PMCID: PMC10642510 DOI: 10.1152/japplphysiol.00458.2023] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Revised: 07/24/2023] [Accepted: 08/03/2023] [Indexed: 08/11/2023] Open
Abstract
Mild intermittent hypoxia may be a potent novel strategy to improve cardiovascular function, motor and cognitive function, and altitude acclimatization. However, there is still a stigma surrounding the field of intermittent hypoxia (IH). Major contributors to this stigma may be due to the overlapping terminology, heterogeneous methodological approaches, and an almost dogmatic focus on different mechanistic underpinnings in different fields of research. Many clinicians and investigators explore the pathophysiological outcomes following long-term exposure to IH in an attempt to improve our understanding of sleep apnea (SA) and develop new treatment plans. However, others use IH as a tool to improve physiological outcomes such as blood pressure, motor function, and altitude acclimatization. Unfortunately, studies investigating the pathophysiology of SA or the potential benefit of IH use similar, unstandardized terminologies facilitating a confusion surrounding IH protocols and the intentions of various studies. In this perspective paper, we aim to highlight IH terminology-related issues with the aim of spurring harmonization of the terminology used in the field of IH research to account for distinct outcomes of hypoxia exposure depending on protocol and individuum.
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Affiliation(s)
- Gino S Panza
- Department of Research and Development, John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan, United States
- Department of Health Care Sciences, Program of Occupational Therapy, Wayne State University, Detroit, Michigan, United States
| | - Johannes Burtscher
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
| | - Fei Zhao
- Department of Research and Development, John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan, United States
- Department of Health Care Sciences, Program of Occupational Therapy, Wayne State University, Detroit, Michigan, United States
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11
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Corbett J, Tipton MJ, Perissiou M, James T, Young JS, Newman A, Cummings M, Montgomery H, Grocott MPW, Shepherd AI. Effect of different levels of acute hypoxia on subsequent oral glucose tolerance in males with overweight: A balanced cross-over pilot feasibility study. Physiol Rep 2023; 11:e15623. [PMID: 37144546 PMCID: PMC10161207 DOI: 10.14814/phy2.15623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 05/06/2023] Open
Abstract
Previous research has shown that ≤60 min hypoxic exposure improves subsequent glycaemic control, but the optimal level of hypoxia is unknown and data are lacking from individuals with overweight. We undertook a cross-over pilot feasibility study investigating the effect of 60-min prior resting exposure to different inspired oxygen fractions (CON FI O2 = 0.209; HIGH FI O2 = 0.155; VHIGH FI O2 = 0.125) on glycaemic control, insulin sensitivity, and oxidative stress during a subsequent oral glucose tolerance test (OGTT) in males with overweight (mean (SD) BMI = 27.6 (1.3) kg/m2 ; n = 12). Feasibility was defined by exceeding predefined withdrawal criteria for peripheral blood oxygen saturation (SpO2 ), partial pressure of end-tidal oxygen or carbon dioxide and acute mountain sickness (AMS), and dyspnoea symptomology. Hypoxia reduced SpO2 in a stepwise manner (CON = 97(1)%; HIGH = 91(1)%; VHIGH = 81(3)%, p < 0.001), but did not affect peak plasma glucose concentration (CON = 7.5(1.8) mmol∙L-1 ; HIGH = 7.7(1.1) mmol∙L-1 ; VHIGH = 7.7(1.1) mmol∙L-1 ; p = 0.777; η2 = 0.013), plasma glucose area under the curve, insulin sensitivity, or metabolic clearance rate of glucose (p > 0.05). We observed no between-conditions differences in oxidative stress (p > 0.05), but dyspnoea and AMS symptoms increased in VHIGH (p < 0.05), with one participant meeting the withdrawal criteria. Acute HIGH or VHIGH exposure prior to an OGTT does not influence glucose homeostasis in males with overweight, but VHIGH is associated with adverse symptomology and reduced feasibility.
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Affiliation(s)
- Jo Corbett
- Extreme Environments Laboratory, School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, UK
| | - Michael J Tipton
- Extreme Environments Laboratory, School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, UK
| | - Maria Perissiou
- Clinical, Health and Rehabilitation Team, School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, UK
| | - Thomas James
- Extreme Environments Laboratory, School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, UK
- Clinical, Health and Rehabilitation Team, School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, UK
| | - John S Young
- National Horizons Centre, Teesside University, Middlesbrough, UK
- School of Health and Life Sciences, Teesside University, Middlesbrough, UK
| | - Alexander Newman
- National Horizons Centre, Teesside University, Middlesbrough, UK
| | - Michael Cummings
- Diabetes and Endocrinology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
| | - Hugh Montgomery
- Centre for Sport Exercise and Health, Dept Medicine, University College London, London, UK
| | - Michael P W Grocott
- Perioperative and Critical Care Theme, NIHR Southampton Biomedical Research Centre, University Hospital Southampton/University of Southampton, Southampton, UK
| | - Anthony I Shepherd
- Clinical, Health and Rehabilitation Team, School of Sport, Health and Exercise Science, University of Portsmouth, Portsmouth, UK
- Diabetes and Endocrinology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UK
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12
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Timon R, Martinez-Guardado I, Brocherie F. Effects of Intermittent Normobaric Hypoxia on Health-Related Outcomes in Healthy Older Adults: A Systematic Review. SPORTS MEDICINE - OPEN 2023; 9:19. [PMID: 36843041 PMCID: PMC9968673 DOI: 10.1186/s40798-023-00560-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 02/05/2023] [Indexed: 02/27/2023]
Abstract
BACKGROUND Aging is a degenerative process that is associated with an increased risk of diseases. Intermittent hypoxia has been investigated in reference to performance and health-related functions enhancement. This systematic review aimed to summarize the effect of either passive or active intermittent normobaric hypoxic interventions compared with normoxia on health-related outcomes in healthy older adults. METHODS Relevant studies were searched from PubMed and Web of Science databases in accordance with PRISMA guidelines (since their inceptions up until August 9, 2022) using the following inclusion criteria: (1) randomized controlled trials, clinical trials and pilot studies; (2) Studies involving humans aged > 50 years old and without any chronic diseases diagnosed; (3) interventions based on in vivo intermittent systemic normobaric hypoxia exposure; (4) articles focusing on the analysis of health-related outcomes (body composition, metabolic, bone, cardiovascular, functional fitness or quality of life). Cochrane Collaboration recommendations were used to assess the risk of bias. RESULTS From 509 articles initially found, 17 studies were included. All interventions were performed in moderate normobaric hypoxia, with three studies using passive exposure, and the others combining intermittent hypoxia with training protocols (i.e., using resistance-, whole body vibration- or aerobic-based exercise). CONCLUSIONS Computed results indicate a limited effect of passive/active intermittent hypoxia (ranging 4-24 weeks, 2-4 days/week, 16-120 min/session, 13-16% of fraction of inspired oxygen or 75-85% of peripheral oxygen saturation) compared to similar intervention in normoxia on body composition, functional fitness, cardiovascular and bone health in healthy older (50-75 years old) adults. Only in specific settings (i.e., intermediate- or long-term interventions with high intensity/volume training sessions repeated at least 3 days per week), may intermittent hypoxia elicit beneficial effects. Further research is needed to determine the dose-response of passive/active intermittent hypoxia in the elderly. TRIAL REGISTRATION SYSTEMATIC REVIEW REGISTRATION PROSPERO 2022 CRD42022338648.
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Affiliation(s)
- Rafael Timon
- Sport Sciences Faculty, Universidad de Extremadura, Av/ Universidad s/n, 10004, Cáceres, Spain.
| | - Ismael Martinez-Guardado
- grid.464701.00000 0001 0674 2310BRABE Group. Faculty of Life and Nature Sciences, Universidad de Nebrija, Madrid, Spain
| | - Franck Brocherie
- grid.418501.90000 0001 2163 2398Laboratory Sport, Expertise and Performance (EA 7370), French Institute of Sport (INSEP), Paris, France
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13
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van Meijel RLJ, Blaak EE, Goossens GH. Effects of hypoxic exercise on 24-hour glucose profile and substrate metabolism in overweight and obese men with impaired glucose metabolism. Am J Physiol Endocrinol Metab 2023; 324:E135-E143. [PMID: 36542847 DOI: 10.1152/ajpendo.00230.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Hypoxic exercise (HE) may have more pronounced effects on glucose homeostasis than exercise under normoxic conditions (NE), but effects on 24-h glucose profile and substrate utilization remain unclear. We investigated the effects of moderate-intensity HE compared with NE on 24-h glucose profile and substrate metabolism in overweight/obese individuals. Ten overweight/obese men with impaired glucose homeostasis participated in a randomized, single-blind, crossover trial. Participants performed moderate-intensity cycling exercise for 4 consecutive days under mild normobaric hypoxic ([Formula: see text]: 15%) or normoxic ([Formula: see text]: 21%) conditions at similar relative exercise intensity (2 × 30 min/day at 50% of maximal heart rate, with a ∼4-wk washout period. Twenty-four-hour glucose levels and systemic oxygen saturation ([Formula: see text]) were monitored throughout the study. At day 5, plasma metabolites and substrate oxidation were determined during a mixed-meal test under normoxic conditions. [Formula: see text] and absolute workload were lower (both P < 0.001), whereas heart rate was comparable during HE compared with NE. HE did not alter mean 24-h, daytime, and nighttime glucose concentrations, and measures of glycemic variability. However, the HE-induced decrease in [Formula: see text] was positively correlated with HE-induced improvements in mean 24-h (rs = 0.683, P = 0.042) and daytime (rs = 0.783, P = 0.013) glucose concentrations. HE at similar relative exercise intensity reduces [Formula: see text] and has comparable effects on mean 24-h glucose concentration and glycemic variability than NE in overweight/obese men with impaired glucose metabolism. Nevertheless, a more pronounced reduction in [Formula: see text] during HE was associated with lower 24-h glucose concentrations, suggesting that a marked hypoxic stimulus is needed to improve glucose homeostasis.NEW & NOTEWORTHY We demonstrate that hypoxic exercise at similar relative exercise intensity (i.e. lower absolute workload) reduces systemic oxygen saturation ([Formula: see text]) and has comparable effects on mean 24-h glucose concentrations and glycemic variability than normoxic exercise in men with overweight/obesity and impaired glucose metabolism. A more pronounced reduction in [Formula: see text] during hypoxic exercise, however, was associated with lower 24-h and daytime glucose concentrations. Our findings suggest that a marked hypoxic stimulus may improve glucose homeostasis.
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Affiliation(s)
- Rens L J van Meijel
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Ellen E Blaak
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Gijs H Goossens
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
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14
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Effectiveness of Intermittent Hypoxia-Hyperoxia Therapy in Different Pathologies with Possible Metabolic Implications. Metabolites 2023; 13:metabo13020181. [PMID: 36837800 PMCID: PMC9961389 DOI: 10.3390/metabo13020181] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 01/22/2023] [Accepted: 01/23/2023] [Indexed: 01/27/2023] Open
Abstract
Intermittent oxygen therapy (IHT), initially used in the hypoxic administration variant, has been shown to be effective in various pathologies studied, from cardiopulmonary to vascular and metabolic pathologies and more. IHT used to prevent and treat various diseases has thus gained more and more attention as the years have passed. The mechanisms underlying the beneficial effects have been investigated at multiple biological levels, from systemic physiological reactions to genomic regulation. In the last decade, a new method of intermittent oxygen therapy has been developed that combines hypoxic and hyperoxic periods. They can be applied both at rest and during physical exercise, hence the specific indications in sports medicine. It has been hypothesized that replacing normoxia with moderate hyperoxia may increase the adaptive response to the intermittent hypoxic stimulus by upregulating reactive oxygen species and hypoxia-inducible genes. This systematic literature review is based on the "Preferred Reporting Items for Systematic Reviews and Meta-Analysis"-"PRISMA"-methodology, the widely internationally accepted method.
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15
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Yuan H, Liu J, Gu Y, Ji X, Nan G. Intermittent hypoxia conditioning as a potential prevention and treatment strategy for ischemic stroke: Current evidence and future directions. Front Neurosci 2022; 16:1067411. [PMID: 36507357 PMCID: PMC9732261 DOI: 10.3389/fnins.2022.1067411] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 11/11/2022] [Indexed: 11/26/2022] Open
Abstract
Ischemic stroke (IS) is the leading cause of disability and death worldwide. Owing to the aging population and unhealthy lifestyles, the incidence of cerebrovascular disease is high. Vascular risk factors include hypertension, diabetes, dyslipidemia, and obesity. Therefore, in addition to timely and effective reperfusion therapy for IS, it is crucial to actively control these risk factors to reduce the incidence and recurrence rates of IS. Evidence from human and animal studies suggests that moderate intermittent hypoxia (IH) exposure is a promising therapeutic strategy to ameliorate common vascular risk factors and comorbidities. Given the complex pathophysiological mechanisms underlying IS, effective treatment must focus on reducing injury in the acute phase and promoting repair in the recovery phase. Therefore, this review discusses the preclinical perspectives on IH conditioning as a potential treatment for neurovascular injury and highlights IH pre and postconditioning strategies for IS. Hypoxia conditioning reduces brain injury by increasing resistance to acute ischemic and hypoxic stress, exerting neuroprotective effects, and promoting post-injury repair and regeneration. However, whether IH produces beneficial effects depends not only on the hypoxic regimen but also on inter-subject differences. Therefore, we discuss the factors that may influence the effectiveness of IH treatment, including age, sex, comorbidities, and circadian rhythm, which can be used to help identify the optimal intervention population and treatment protocols for more accurate, individualized clinical translation. In conclusion, IH conditioning as a non-invasive, non-pharmacological, systemic, and multi-targeted intervention can not only reduce brain damage after stroke but can also be applied to the prevention and functional recovery of IS, providing brain protection at different stages of the disease. It represents a promising therapeutic strategy. For patients with IS and high-risk groups, IH conditioning is expected to develop as an adjunctive clinical treatment option to reduce the incidence, recurrence, disability, and mortality of IS and to reduce disease burden.
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Affiliation(s)
- Honghua Yuan
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jia Liu
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, China
| | - Yuhang Gu
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xunming Ji
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, China,Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China,*Correspondence: Xunming Ji,
| | - Guangxian Nan
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China,Guangxian Nan,
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16
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Burtscher J, Mallet RT, Pialoux V, Millet GP, Burtscher M. Adaptive Responses to Hypoxia and/or Hyperoxia in Humans. Antioxid Redox Signal 2022; 37:887-912. [PMID: 35102747 DOI: 10.1089/ars.2021.0280] [Citation(s) in RCA: 73] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Significance: Oxygen is indispensable for aerobic life, but its utilization exposes cells and tissues to oxidative stress; thus, tight regulation of cellular, tissue, and systemic oxygen concentrations is crucial. Here, we review the current understanding of how the human organism (mal-)adapts to low (hypoxia) and high (hyperoxia) oxygen levels and how these adaptations may be harnessed as therapeutic or performance enhancing strategies at the systemic level. Recent Advances: Hyperbaric oxygen therapy is already a cornerstone of modern medicine, and the application of mild hypoxia, that is, hypoxia conditioning (HC), to strengthen the resilience of organs or the whole body to severe hypoxic insults is an important preparation for high-altitude sojourns or to protect the cardiovascular system from hypoxic/ischemic damage. Many other applications of adaptations to hypo- and/or hyperoxia are only just emerging. HC-sometimes in combination with hyperoxic interventions-is gaining traction for the treatment of chronic diseases, including numerous neurological disorders, and for performance enhancement. Critical Issues: The dose- and intensity-dependent effects of varying oxygen concentrations render hypoxia- and/or hyperoxia-based interventions potentially highly beneficial, yet hazardous, although the risks versus benefits are as yet ill-defined. Future Directions: The field of low and high oxygen conditioning is expanding rapidly, and novel applications are increasingly recognized, for example, the modulation of aging processes, mood disorders, or metabolic diseases. To advance hypoxia/hyperoxia conditioning to clinical applications, more research on the effects of the intensity, duration, and frequency of altered oxygen concentrations, as well as on individual vulnerabilities to such interventions, is paramount. Antioxid. Redox Signal. 37, 887-912.
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Affiliation(s)
- Johannes Burtscher
- Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.,Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Robert T Mallet
- Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA
| | - Vincent Pialoux
- Inter-University Laboratory of Human Movement Biology EA7424, University Claude Bernard Lyon 1, University of Lyon, Lyon, France
| | - Grégoire P Millet
- Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.,Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
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17
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Behrendt 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 MEDICINE - OPEN 2022; 8:70. [PMID: 35639211 PMCID: PMC9156652 DOI: 10.1186/s40798-022-00450-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 04/17/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Intermittent hypoxia applied at rest or in combination with exercise promotes multiple beneficial adaptations with regard to performance and health in humans. It was hypothesized that replacing normoxia by moderate hyperoxia can increase the adaptive response to the intermittent hypoxic stimulus. OBJECTIVE Our objective was to systematically review the current state of the literature on the effects of chronic intermittent hypoxia-hyperoxia (IHH) on performance- and health-related outcomes in humans. METHODS PubMed, Web of Science™, Scopus, and Cochrane Library databases were searched in accordance with PRISMA guidelines (January 2000 to September 2021) using the following inclusion criteria: (1) original research articles involving humans, (2) investigation of the chronic effect of IHH, (3) inclusion of a control group being not exposed to IHH, and (4) articles published in peer-reviewed journals written in English. RESULTS Of 1085 articles initially found, eight studies were included. IHH was solely performed at rest in different populations including geriatric patients (n = 1), older patients with cardiovascular (n = 3) and metabolic disease (n = 2) or cognitive impairment (n = 1), and young athletes with overtraining syndrome (n = 1). The included studies confirmed the beneficial effects of chronic exposure to IHH, showing improvements in exercise tolerance, peak oxygen uptake, and global cognitive functions, as well as lowered blood glucose levels. A trend was discernible that chronic exposure to IHH can trigger a reduction in systolic and diastolic blood pressure. The evidence of whether IHH exerts beneficial effects on blood lipid levels and haematological parameters is currently inconclusive. A meta-analysis was not possible because the reviewed studies had a considerable heterogeneity concerning the investigated populations and outcome parameters. CONCLUSION Based on the published literature, it can be suggested that chronic exposure to IHH might be a promising non-pharmacological intervention strategy for improving peak oxygen consumption, exercise tolerance, and cognitive performance as well as reducing blood glucose levels, and systolic and diastolic blood pressure in older patients with cardiovascular and metabolic diseases or cognitive impairment. However, further randomized controlled trials with adequate sample sizes are needed to confirm and extend the evidence. This systematic review was registered on the international prospective register of systematic reviews (PROSPERO-ID: CRD42021281248) ( https://www.crd.york.ac.uk/prospero/ ).
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Affiliation(s)
- Tom Behrendt
- Department of Sport Science, Chair for Health and Physical Activity, Otto-von-Guericke University Magdeburg, Universitätsplatz 2, 39104 Magdeburg, Germany
| | - Robert Bielitzki
- Department of Sport Science, Chair for Health and Physical Activity, Otto-von-Guericke University Magdeburg, Universitätsplatz 2, 39104 Magdeburg, Germany
| | - Martin Behrens
- Department of Sport Science, Chair for Health and Physical Activity, Otto-von-Guericke University Magdeburg, Universitätsplatz 2, 39104 Magdeburg, Germany
- Department of Orthopaedics, Rostock University Medical Center, Doberaner Str. 142, 18057 Rostock, Germany
| | - Fabian Herold
- Research Group Degenerative and Chronic Disease, Movement, Faculty of Health Sciences, University of Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany
| | - Lutz Schega
- Department of Sport Science, Chair for Health and Physical Activity, Otto-von-Guericke University Magdeburg, Universitätsplatz 2, 39104 Magdeburg, Germany
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Tessema 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. [PMID: 35677200 PMCID: PMC9168371 DOI: 10.3389/fnagi.2022.878278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 04/21/2022] [Indexed: 11/13/2022] Open
Abstract
Several studies have assessed the effects of intermittent hypoxia-normoxia training (IHNT), intermittent hypoxia-hyperoxia training (IHHT), and obstructive sleep apnea (OSA) on aging and age-related diseases in humans; however, the results remain contradictory. Therefore, this review aims to systematically summarize the available studies on the effects of IHNT, IHHT, and OSA on aging and age-related diseases. Relevant studies were searched from PubMed, Google Scholar, Cochrane Library databases, and through manual searching from reference lists of eligible studies. A total of 38 eligible studies were included in this systematic review. IHHT and IHNT provide positive effects on several age-related parameters including quality of life, cognitive and physical functions, plasma level of glucose and cholesterol/LDL, systolic blood pressure, red blood cells, and inflammation. Moreover, moderate intermittent hypoxia induces telomerase reverse transcriptase (TERT) activity and telomere stabilization, delays induction of senescence-associated markers expression and senescence-associated β-galactosidase, upregulates pluripotent marker (Oct4), activates a metabolic shift, and raises resistance to pro-apoptotic stimuli. On the contrary, intermittent hypoxia in OSA causes hypertension, metabolic syndrome, vascular function impairment, quality of life and cognitive scores reduction, advanced brain aging, increase in insulin resistance, plasma hydrogen peroxide, GSH, IL-6, hsCRP, leptin, and leukocyte telomere shortening. Thus, it can be speculated that the main factor that determines the direction of the intermittent hypoxia action is the intensity and duration of exposure. There is no direct study to prove that IHNT/IHHT actually increases life expectancy in humans. Therefore, further study is needed to investigate the actual effect of IHNT/IHHT on aging in humans.Systematic Review Registrationwww.crd.york.ac.uk/prospero, identifier CRD42022298499.
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Affiliation(s)
- Belay Tessema
- Institute of Clinical Immunology, Faculty of Medicine, Leipzig University, Leipzig, Germany
- Institute of Medical Microbiology and Epidemiology of Infectious Diseases, Faculty of Medicine, Leipzig University, Leipzig, Germany
- Department of Medical Microbiology, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia
- *Correspondence: Belay Tessema, ,
| | - Ulrich Sack
- Institute of Clinical Immunology, Faculty of Medicine, Leipzig University, Leipzig, Germany
| | - Brigitte König
- Institute of Medical Microbiology and Epidemiology of Infectious Diseases, Faculty of Medicine, Leipzig University, Leipzig, Germany
| | - Zoya Serebrovska
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
| | - Egor Egorov
- IPAM Institute for Preventive and Anti-Aging Medicine, Berlin, Germany
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Panza GS, Puri S, Lin HS, Badr MS, Mateika JH. Daily Exposure to Mild Intermittent Hypoxia Reduces Blood Pressure in Male Patients with Obstructive Sleep Apnea and Hypertension. Am J Respir Crit Care Med 2022; 205:949-958. [PMID: 35015980 PMCID: PMC9838631 DOI: 10.1164/rccm.202108-1808oc] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Rationale: Daily exposure to mild intermittent hypoxia (MIH) may elicit beneficial cardiovascular outcomes. Objectives: To determine the effect of 15 days of MIH and in-home continuous positive airway pressure treatment on blood pressure in participants with obstructive sleep apnea and hypertension. Methods: We administered MIH during wakefulness 5 days/week for 3 weeks. The protocol consisted of twelve 2-minute bouts of hypoxia interspersed with 2 minutes of normoxia. End-tidal carbon dioxide was maintained 2 mm Hg above baseline values throughout the protocol. Control participants were exposed to a sham protocol (i.e., compressed air). All participants were treated with continuous positive airway pressure over the 3-week period. Results are mean ± SD. Measurements and Main Results: Sixteen male participants completed the study (experimental n = 10; control n = 6). Systolic blood pressure at rest during wakefulness over 24 hours was reduced after 15 days of MIH (142.9 ± 8.6 vs. 132.0 ± 10.7 mm Hg; P < 0.001), but not following the sham protocol (149.9 ± 8.6 vs. 149.7 ± 10.8 mm Hg; P = 0.915). Thus, the reduction in blood pressure from baseline was greater in the experimental group compared with control (-10.91 ± 4.1 vs. -0.17 ± 3.6 mm Hg; P = 0.003). Modifications in blood pressure were accompanied by increased parasympathetic and reduced sympathetic activity in the experimental group, as estimated by blood pressure and heart rate variability analysis. No detrimental neurocognitive and metabolic outcomes were evident following MIH. Conclusions: MIH elicits beneficial cardiovascular and autonomic outcomes in males with OSA and concurrent hypertension. Clinical trial registered with www.clinicaltrials.gov (NCT03736382).
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Affiliation(s)
- Gino S. Panza
- John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan; and,Department of Physiology
| | - Shipra Puri
- John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan; and,Department of Physiology
| | - Ho-Sheng Lin
- John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan; and,Department of Otolaryngology, and
| | - M. Safwan Badr
- John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan; and,Department of Physiology,,Department of Internal Medicine, School of Medicine, Wayne State University, Detroit, Michigan
| | - Jason H. Mateika
- John D. Dingell Veterans Affairs Medical Center, Detroit, Michigan; and,Department of Physiology,,Department of Internal Medicine, School of Medicine, Wayne State University, Detroit, Michigan
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Serebrovska ZO, Xi L, Tumanovska LV, Shysh AM, Goncharov SV, Khetsuriani M, Kozak TO, Pashevin DA, Dosenko VE, Virko SV, Kholin VA, Grib ON, Utko NA, Egorov E, Polischuk AO, Serebrovska TV. Response of Circulating Inflammatory Markers to Intermittent Hypoxia-Hyperoxia Training in Healthy Elderly People and Patients with Mild Cognitive Impairment. Life (Basel) 2022; 12:life12030432. [PMID: 35330183 PMCID: PMC8953753 DOI: 10.3390/life12030432] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Revised: 03/11/2022] [Accepted: 03/14/2022] [Indexed: 12/28/2022] Open
Abstract
Intermittent hypoxia-hyperoxia training (IHHT) is a non-pharmacological therapeutic modality for management of some chronic- and age-related pathologies, such as Alzheimer’s disease (AD). Our previous studies demonstrated significant improvement of cognitive function after IHHT in the patients with mild cognitive impairment (MCI). The present study further investigated the effects of IHHT on pro-inflammatory factors in healthy elderly individuals and patients with early signs of AD. Twenty-nine subjects (13 healthy subjects without signs of cognitive impairment syndrome and 16 patients diagnosed with MCI; age 52 to 76 years) were divided into four groups: Healthy+Sham (n = 7), Healthy+IHHT (n = 6), MCI+Sham (n = 6), and MCI+IHHT (n = 10). IHHT was carried out 5 days per week for 3 weeks (total 15 sessions), and each daily session included 4 cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Decline in cognitive function indices was observed initially in both MCI+Sham and MCI+IHHT groups. The sham training did not alter any of the parameters, whereas IHHT resulted in improvement in latency of cognitive evoked potentials, along with elevation in APP110, GDF15 expression, and MMP9 activity in both healthy subjects and those with MCI. Increased MMP2 activity, HMGB1, and P-selectin expression and decreased NETs formation and Aβ expression were also observed in the MCI+IHHT group. There was a negative correlation between MoCA score and the plasma GDF15 expression (R = −0.5799, p < 0.05) before the initiation of IHHT. The enhanced expression of GDF15 was also associated with longer latency of the event-related potentials P330 and N200 (R = 0.6263, p < 0.05 and R = 0.5715, p < 0.05, respectively). In conclusion, IHHT upregulated circulating levels of some inflammatory markers, which may represent potential triggers for cellular adaptive reprogramming, leading to therapeutic effects against cognitive dysfunction and neuropathological changes during progression of AD. Further investigation is needed to clarify if there is a causative relationship between the improved cognitive function and the elevated inflammatory markers following IHHT.
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Affiliation(s)
- Zoya O. Serebrovska
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; (L.V.T.); (A.M.S.); (S.V.G.); (M.K.); (T.O.K.); (D.A.P.); (V.E.D.); (A.O.P.); (T.V.S.)
- Correspondence: (Z.O.S.); (L.X.)
| | - Lei Xi
- Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0204, USA
- Correspondence: (Z.O.S.); (L.X.)
| | - Lesya V. Tumanovska
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; (L.V.T.); (A.M.S.); (S.V.G.); (M.K.); (T.O.K.); (D.A.P.); (V.E.D.); (A.O.P.); (T.V.S.)
| | - Angela M. Shysh
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; (L.V.T.); (A.M.S.); (S.V.G.); (M.K.); (T.O.K.); (D.A.P.); (V.E.D.); (A.O.P.); (T.V.S.)
| | - Sergii V. Goncharov
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; (L.V.T.); (A.M.S.); (S.V.G.); (M.K.); (T.O.K.); (D.A.P.); (V.E.D.); (A.O.P.); (T.V.S.)
| | - Michael Khetsuriani
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; (L.V.T.); (A.M.S.); (S.V.G.); (M.K.); (T.O.K.); (D.A.P.); (V.E.D.); (A.O.P.); (T.V.S.)
| | - Taisia O. Kozak
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; (L.V.T.); (A.M.S.); (S.V.G.); (M.K.); (T.O.K.); (D.A.P.); (V.E.D.); (A.O.P.); (T.V.S.)
| | - Denis A. Pashevin
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; (L.V.T.); (A.M.S.); (S.V.G.); (M.K.); (T.O.K.); (D.A.P.); (V.E.D.); (A.O.P.); (T.V.S.)
| | - Victor E. Dosenko
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; (L.V.T.); (A.M.S.); (S.V.G.); (M.K.); (T.O.K.); (D.A.P.); (V.E.D.); (A.O.P.); (T.V.S.)
| | - Sergii V. Virko
- Lashkariov Institute of Semiconductor Physics, National Academy of Sciences, 41 Nauki Ave., 03028 Kyiv, Ukraine;
| | - Viktor A. Kholin
- Department of Age Physiology and Pathology of Nervous System, Chebotarev Institute of Gerontology NAMS of Ukraine, 04114 Kyiv, Ukraine; (V.A.K.); (O.N.G.); (N.A.U.)
| | - Oksana N. Grib
- Department of Age Physiology and Pathology of Nervous System, Chebotarev Institute of Gerontology NAMS of Ukraine, 04114 Kyiv, Ukraine; (V.A.K.); (O.N.G.); (N.A.U.)
| | - Natalie A. Utko
- Department of Age Physiology and Pathology of Nervous System, Chebotarev Institute of Gerontology NAMS of Ukraine, 04114 Kyiv, Ukraine; (V.A.K.); (O.N.G.); (N.A.U.)
| | - Egor Egorov
- CELLGYM Technologies GmbH, 14193 Berlin, Germany;
| | - Anna O. Polischuk
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; (L.V.T.); (A.M.S.); (S.V.G.); (M.K.); (T.O.K.); (D.A.P.); (V.E.D.); (A.O.P.); (T.V.S.)
| | - Tetiana V. Serebrovska
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, 01024 Kyiv, Ukraine; (L.V.T.); (A.M.S.); (S.V.G.); (M.K.); (T.O.K.); (D.A.P.); (V.E.D.); (A.O.P.); (T.V.S.)
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21
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Hormonal and metabolic responses of older adults to resistance training in normobaric hypoxia. Eur J Appl Physiol 2022; 122:1007-1017. [PMID: 35142944 DOI: 10.1007/s00421-022-04897-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 01/06/2022] [Indexed: 11/03/2022]
Abstract
PURPOSE In young adults, the hormonal responses to resistance exercise are amplified by normobaric hypoxia. Hormone concentrations and metabolism are typically dysregulated with age, yet the impact of hypoxia on these responses to resistance exercise are uncharacterised. Therefore, this study aimed to characterise the acute and chronic hormonal and metabolic responses of older adults to resistance training in normobaric hypoxia. METHODS Adults aged 60-75 years completed 8 weeks of resistance training in either normoxia (20.9% O2; n = 10) or normobaric hypoxia (14.4% O2, n = 10) twice weekly at 70% of their predicted 1-repetition maximum. Growth hormone, glucose, lactate, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), cortisol, total testosterone, adrenaline, noradrenaline and dopamine were quantified at pre- and post-training, and in the 60 min following the first training session (untrained state) and the last training session (trained state). RESULTS Eight weeks of training in hypoxia did not affect the resting levels of the hormones or physiological factors measured. However, hypoxia significantly blunted the acute growth hormone response in the 15 min following the last training session at week eight (43.87% lower in the hypoxic group; p = 0.017). This novel and unexpected finding requires further investigation. All other hormones were unaffected acutely by hypoxia in the 60 min following the first and the last training session. CONCLUSION Chronic resistance training in normobaric hypoxia supresses the growth hormone response to exercise in older adults. All other hormones and metabolic markers were unaffected both acutely and chronically by hypoxia.
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22
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Guan Y, Liu J, Gu Y, Ji X. Effects of Hypoxia on Cerebral Microvascular Angiogenesis: Benefits or Damages? Aging Dis 2022; 14:370-385. [PMID: 37008044 PMCID: PMC10017152 DOI: 10.14336/ad.2022.0902] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 09/02/2022] [Indexed: 11/18/2022] Open
Abstract
Cerebrovascular microcirculation is essential for maintaining the physiological functions of the brain. The brain can be protected from stress injury by remodeling the microcirculation network. Angiogenesis is a type of cerebral vascular remodeling. It is an effective approach to improve the blood flow of the cerebral microcirculation, which is necessary for preventing and treating various neurological disorders. Hypoxia is one of the most important regulators of angiogenesis, affecting the sprouting, proliferation, and maturation stages of angiogenesis. Moreover, hypoxia negatively affects cerebral vascular tissue by impairing the structural and functional integrity of the blood-brain barrier and vascular-nerve decoupling. Therefore, hypoxia has a dual effect on blood vessels and is affected by confounding factors including oxygen concentration, hypoxia duration, and hypoxia frequency and extent. Establishing an optimal model that promotes cerebral microvasculogenesis without causing vascular injury is essential. In this review, we first elaborate on the effects of hypoxia on blood vessels from two different perspectives: (1) the promotion of angiogenesis and (2) cerebral microcirculation damage. We further discuss the factors influencing the dual role of hypoxia and emphasize the benefits of moderate hypoxic irritation and its potential application as an easy, safe, and effective treatment for multiple nervous system disorders.
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Affiliation(s)
- Yuying Guan
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, China
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Jia Liu
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, China
| | - Yakun Gu
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, China
| | - Xunming Ji
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data-based Precision Medicine, Capital Medical University, Beijing, China
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China
- Correspondence should be addressed to: Dr. Prof. Xunming Ji; Beijing Institute of Brain Disorders, Capital Medical University, 10 Xi Tou Tiao, You Anmen, Beijing 100069, China. E-mail: .
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Afina AB, Oleg SG, Alexander AB, Ines D, Alexander Yu S, Nikita VV, Denis ST, Daria GG, Zhang Y, Chavdar SP, Dmitriy VG, Elena AS, Irina VK, Philippe Yu K. The Effects of Intermittent Hypoxic-Hyperoxic Exposures on Lipid Profile and Inflammation in Patients With Metabolic Syndrome. Front Cardiovasc Med 2021; 8:700826. [PMID: 34513946 PMCID: PMC8429814 DOI: 10.3389/fcvm.2021.700826] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 07/23/2021] [Indexed: 12/18/2022] Open
Abstract
Background: Patients with metabolic syndrome (MS) tend to suffer from comorbidities, and are often simultaneously affected by obesity, dysglycemia, hypertension, and dyslipidemia. This syndrome can be reversed if it is timely diagnosed and treated with a combination of risk factors-reducing lifestyle changes and a tailored pharmacological plan. Interval hypoxic-hyperoxic training (IHHT) has been shown as an effective program in reducing cardiovascular risk factors in patients with MS even in the absence of exercise. However, the influence of IHHT on the lipid profile and inflammation in this clinical population remains relatively unknown. Methods: A prospective, single-center, randomized controlled trial was conducted on 65 (33 men) patients with MS aged 29–74 years, who were randomly allocated to the IHHT or control (sham) experimental groups. The IHHT group completed a 3-week, 5 days/week intermittent exposure to hypoxia and hyperoxia. The control (sham) group followed the same protocol but was breathing room air instead. The primary endpoints were the lipid profile (concentrations of total cholesterol [TC], low-density lipoprotein [LDL], high-density lipoprotein [HDL], and triglycerides [TG]) and the inflammatory factors such as high-sensitivity C-reactive protein (hs-CRP), galectin-3, heat shock proteins (Hsp70). The secondary endpoints were alanine aminotransferase (ALT), aspartate aminotransferase (AST), N-terminal pro-hormone of brain natriuretic peptide level (NTproBNP), transforming growth factor beta-1 (TGF-beta1), heart-type fatty acid-binding protein (H-FABP), and nitric oxide synthase 2 (NOS2). Results: There were no differences between the two groups but the different baseline values have affected these results. The IHHT group demonstrated pre-post decrease in total cholesterol (p = 0.001), LDL (p = 0.001), and TG levels (p = 0.001). We have also found a decrease in the CRP-hs (p = 0.015) and Hsp70 (p = 0.006) in IHHT-group after intervention, and a significant decrease in pre-post (delta) differences of NTproBNP (p < 0.0001) in the IHHT group compared to the control group. In addition, the patients of the IHHT group showed a statistically significant decrease in pre-post differences of ALT and AST levels in comparison with the control group (p = 0.001). No significant IHHT complications or serious adverse events were observed. Conclusions: The IHHT appears to improve lipid profile and anti-inflammatory status. It is a safe, well-tolerated procedure, and could be recommended as an auxiliary treatment in patients suffering from MS, however, the experiment results were limited by the baseline group differences. Clinical Trial Registration:ClinicalTrials.gov, identifier [NCT04791397]. Evaluation of the effect of IHHT on vascular stiffness and elasticity of the liver tissue in patients with MS.
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Affiliation(s)
- A Bestavashvili Afina
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - S Glazachev Oleg
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - A Bestavashvili Alexander
- Department of Facultative Therapy, A.I. Nesterov of Medical Faculty, Pirogov Russian National Research Medical University, Moscow, Russia
| | - Dhif Ines
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - Suvorov Alexander Yu
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - V Vorontsov Nikita
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - S Tuter Denis
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - G Gognieva Daria
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - Yong Zhang
- Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin, China
| | - S Pavlov Chavdar
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - V Glushenkov Dmitriy
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - A Sirkina Elena
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - V Kaloshina Irina
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
| | - Kopylov Philippe Yu
- Department of Cardiology, Functional and Ultrasound Diagnostics, N.V. Sklifosofsky, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.,World-Class Research Center "Digital Biodesign and Personalized Healthcare", I. M. Sechenov First Moscow State Medical University, Moscow, Russia
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Lopez-Pascual A, Trayhurn P, Martínez JA, González-Muniesa P. Oxygen in Metabolic Dysfunction and Its Therapeutic Relevance. Antioxid Redox Signal 2021; 35:642-687. [PMID: 34036800 DOI: 10.1089/ars.2019.7901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Significance: In recent years, a number of studies have shown altered oxygen partial pressure at a tissue level in metabolic disorders, and some researchers have considered oxygen to be a (macro) nutrient. Oxygen availability may be compromised in obesity and several other metabolism-related pathological conditions, including sleep apnea-hypopnea syndrome, the metabolic syndrome (which is a set of conditions), type 2 diabetes, cardiovascular disease, and cancer. Recent Advances: Strategies designed to reduce adiposity and its accompanying disorders have been mainly centered on nutritional interventions and physical activity programs. However, novel therapies are needed since these approaches have not been sufficient to counteract the worldwide increasing rates of metabolic disorders. In this regard, intermittent hypoxia training and hyperoxia could be potential treatments through oxygen-related adaptations. Moreover, living at a high altitude may have a protective effect against the development of abnormal metabolic conditions. In addition, oxygen delivery systems may be of therapeutic value for supplying the tissue-specific oxygen requirements. Critical Issues: Precise in vivo methods to measure oxygenation are vital to disentangle some of the controversies related to this research area. Further, it is evident that there is a growing need for novel in vitro models to study the potential pathways involved in metabolic dysfunction to find appropriate therapeutic targets. Future Directions: Based on the existing evidence, it is suggested that oxygen availability has a key role in obesity and its related comorbidities. Oxygen should be considered in relation to potential therapeutic strategies in the treatment and prevention of metabolic disorders. Antioxid. Redox Signal. 35, 642-687.
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Affiliation(s)
- Amaya Lopez-Pascual
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.,Neuroendocrine Cell Biology, Lund University Diabetes Centre, Lund University, Malmö, Sweden
| | - Paul Trayhurn
- Obesity Biology Unit, University of Liverpool, Liverpool, United Kingdom.,Clore Laboratory, The University of Buckingham, Buckingham, United Kingdom
| | - J Alfredo Martínez
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.,IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.,CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, Madrid, Spain.,Precision Nutrition and Cardiometabolic Health, IMDEA Food, Madrid Institute for Advanced Studies, Madrid, Spain
| | - Pedro González-Muniesa
- Department of Nutrition, Food Science and Physiology, School of Pharmacy and Nutrition, Centre for Nutrition Research, University of Navarra, Pamplona, Spain.,IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.,CIBERobn Physiopathology of Obesity and Nutrition, Centre of Biomedical Research Network, ISCIII, Madrid, Spain
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van 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; 22:471-483. [PMID: 33851320 PMCID: PMC8087568 DOI: 10.1007/s11154-021-09654-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/06/2021] [Indexed: 02/06/2023]
Abstract
Humans living at a higher altitude are less prone to suffer from impaired glucose homeostasis and type 2 diabetes mellitus (T2DM), which might at least partly be explained by lower oxygen availability at higher altitudes. The present systematic review aimed to provide an overview of the current literature on the effects of hypoxia exposure on glucose homeostasis in metabolically compromised humans. Several databases were searched up to August 10th, 2020. The search strategy identified 368 unique records. Following assessment for eligibility based on the selection criteria, 16 studies were included in this review. Six studies (2 controlled studies; 4 uncontrolled studies) demonstrated beneficial effects of hypoxia exposure on glucose homeostasis, while 10 studies (8 controlled studies; 2 uncontrolled studies) reported no improvement in glucose homeostasis following hypoxia exposure. Notably, passive hypoxia exposure seemed to improve glucose homeostasis, whereas hypoxic exercise training (2-8 weeks) appeared to have no additional/synergistic effects on glucose homeostasis compared to normoxia exposure. Due to the heterogeneity in study populations and intervention duration (acute studies / 2-8 wks training), it is difficult to indicate which factors may explain conflicting study outcomes. Moreover, these results should be interpreted with some caution, as several studies did not include a control group. Taken together, hypoxia exposure under resting and exercise conditions might provide a novel therapeutic strategy to improve glucose homeostasis in metabolically compromised individuals, but more randomized controlled trials are warranted before strong conclusions on the effects of hypoxia exposure on glucose homeostasis can be drawn.
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Affiliation(s)
- Veerle van Hulten
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
- Department of Clinical Pharmacology and Toxicology, CARIM School for Cardiovascular Diseases, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Rens L J van Meijel
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Gijs H Goossens
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, The Netherlands.
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Kim SW, Jung WS, Chung S, Park HY. Exercise intervention under hypoxic condition as a new therapeutic paradigm for type 2 diabetes mellitus: A narrative review. World J Diabetes 2021; 12:331-343. [PMID: 33889283 PMCID: PMC8040082 DOI: 10.4239/wjd.v12.i4.331] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 01/25/2021] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
This review aims to summarize the health benefits of exposure to hypoxic conditions during exercise in patients with type 2 diabetes mellitus (T2DM). Exposure to hypoxic conditions during exercise training positively changes the physiological response in healthy subjects. Exposure to hypoxic conditions during exercise could markedly increase skeletal muscle glucose uptake compared to that in normoxic conditions. Furthermore, post-exercise insulin sensitivity of T2DM patients increases more when exercising under hypoxic than under normoxic conditions. Regular exercise under short-term hypoxic conditions can improve blood glucose control at lower workloads than in normoxic conditions. Additionally, exercise training under short-term hypoxic conditions can maximize weight loss in overweight and obese patients. Previous studies on healthy subjects have reported that regular exercise under hypoxic conditions had a more positive effect on vascular health than exercising under normoxic conditions. However, currently, evidence indicating that exposure to hypoxic conditions could positively affect T2DM patients in the long-term is lacking. Therefore, further evaluations of the beneficial effects of exercise under hypoxic conditions on the human body, considering different cycle lengths, duration of exposures, sessions per day, and the number of days, are necessary. In this review, we conclude that there is evidence that exercise under hypoxic conditions can yield health benefits, which is potentially valuable in terms of clinical care as a new intervention for T2DM patients.
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Affiliation(s)
- Sung-Woo Kim
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul 05029, South Korea
| | - Won-Sang Jung
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul 05029, South Korea
| | - Sochung Chung
- Department of Pediatrics, Konkuk University Medical Center, Research Institute of Medical Science, Konkuk University, School of Medicine, Seoul 05029, South Korea
| | - Hun-Young Park
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul 05029, South Korea
- Department of Sports Science and Medicine, Konkuk University, Seoul 05029, South Korea
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Kamat SM, Mendelsohn AR, Larrick JW. Rejuvenation Through Oxygen, More or Less. Rejuvenation Res 2021; 24:158-163. [PMID: 33784834 DOI: 10.1089/rej.2021.0014] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Modest modulation of oxygen intake, either by inducing mild intermittent hypoxia or hyperoxia appears to induce modest rejuvenative changes in mammals, in part, by activating key regulator hypoxia-induced factor 1a (HIF-1a). Interestingly both lower oxygen and transient higher oxygen levels induce this hypoxia regulator. Hyperbaric oxygen induces HIF-1a by the hyperoxic-hypoxic paradox that results from an overinduction of protective factors under intermittent hyperoxic conditions, leading to a state somewhat similar to that induced by hypoxia. A key difference being that SIRT1 is induced by hyperoxia, whereas it is reduced during hypoxia by the activity of HIF-1a. In a recent report, a small clinical trial employing 60 sessions of intermittent hyperbaric oxygen therapy (HBOT) studying old humans resulted in increased mean telomere length of immune cells including B cells, natural killer cells, T helper, and cytotoxic T lymphocytes. Moreover, there was a reduction in CD28null senescent T helper and cytotoxic T cells. In a parallel report, HBOT has been reported to enhance cognition in older adults, especially attention and information processing speed through increased cerebral blood flow (CBF) in brain regions where CBF tends to decline with age. The durability of these beneficial changes is yet to be determined. These preliminary results require follow-up, including more extensive characterization of changes in aging-associated biomarkers. An interesting avenue of potential work is to elucidate potential connections between hypoxia and epigenetics, especially the induction of the master pluripotent regulatory factors, which when expressed transiently have been reported to ameliorate some aging biomarkers and pathologies.
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Puri S, Panza G, Mateika JH. A comprehensive review of respiratory, autonomic and cardiovascular responses to intermittent hypoxia in humans. Exp Neurol 2021; 341:113709. [PMID: 33781731 PMCID: PMC8527806 DOI: 10.1016/j.expneurol.2021.113709] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 02/17/2021] [Accepted: 03/24/2021] [Indexed: 01/08/2023]
Abstract
This review explores forms of respiratory and autonomic plasticity, and associated outcome measures, that are initiated by exposure to intermittent hypoxia. The review focuses primarily on studies that have been completed in humans and primarily explores the impact of mild intermittent hypoxia on outcome measures. Studies that have explored two forms of respiratory plasticity, progressive augmentation of the hypoxic ventilatory response and long-term facilitation of ventilation and upper airway muscle activity, are initially reviewed. The role these forms of plasticity might have in sleep disordered breathing are also explored. Thereafter, the role of intermittent hypoxia in the initiation of autonomic plasticity is reviewed and the role this form of plasticity has in cardiovascular and hemodynamic responses during and following intermittent hypoxia is addressed. The role of these responses in individuals with sleep disordered breathing and spinal cord injury are subsequently addressed. Ultimately an integrated picture of the respiratory, autonomic and cardiovascular responses to intermittent hypoxia is presented. The goal of the integrated picture is to address the types of responses that one might expect in humans exposed to one-time and repeated daily exposure to mild intermittent hypoxia. This form of intermittent hypoxia is highlighted because of its potential therapeutic impact in promoting functional improvement and recovery in several physiological systems.
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Affiliation(s)
- Shipra Puri
- John D. Dingell Veterans Affairs Medical Center, Detroit, MI 48201, United States of America; Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, United States of America
| | - Gino Panza
- John D. Dingell Veterans Affairs Medical Center, Detroit, MI 48201, United States of America; Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, United States of America
| | - Jason H Mateika
- John D. Dingell Veterans Affairs Medical Center, Detroit, MI 48201, United States of America; Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, United States of America; Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI 48201, United States of America.
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Hypoxia, HIF-1α, and COVID-19: from pathogenic factors to potential therapeutic targets. Acta Pharmacol Sin 2020; 41:1539-1546. [PMID: 33110240 PMCID: PMC7588589 DOI: 10.1038/s41401-020-00554-8] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 10/08/2020] [Indexed: 02/07/2023]
Abstract
The pandemic of coronavirus disease 2019 (COVID-19) and its pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the greatest current threat to global public health. The highly infectious SARS-CoV-2 virus primarily attacks pulmonary tissues and impairs gas exchange leading to acute respiratory distress syndrome (ARDS) and systemic hypoxia. The current pharmacotherapies for COVID-19 largely rely on supportive and anti-thrombi treatment and the repurposing of antimalarial and antiviral drugs such as hydroxychloroquine and remdesivir. For a better mechanistic understanding of COVID-19, our present review focuses on its primary pathophysiologic features: hypoxia and cytokine storm, which are a prelude to multiple organ failure and lethality. We discussed a possible link between the activation of hypoxia inducible factor 1α (HIF-1α) and cell entry of SARS-CoV-2, since HIF-1α is shown to suppress the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) and upregulate disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). In addition, the protein targets of HIF-1α are involved with the activation of pro-inflammatory cytokine expression and the subsequent inflammatory process. Furthermore, we hypothesized a potential utility of so-called "hypoxic conditioning" to activate HIF-1α-induced cytoprotective signaling for reduction of illness severity and improvement of vital organ function in patients with COVID-19. Taken together, we would propose further investigations into the hypoxia-related molecular mechanisms, from which novel targeted therapies can be developed for the improved management of COVID-19.
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Kang I, Kondo D, Kim J, Lyoo IK, Yurgelun-Todd D, Hwang J, Renshaw PF. Elevating the level of hypoxia inducible factor may be a new potential target for the treatment of depression. Med Hypotheses 2020; 146:110398. [PMID: 33246695 DOI: 10.1016/j.mehy.2020.110398] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Accepted: 11/09/2020] [Indexed: 12/28/2022]
Abstract
Hypoxia inducible factor-1 (HIF-1) is a transcriptional factor that regulates gene expressions in response to decreased oxygen levels in the tissue, or hypoxia. HIF-1 exerts protective effects against hypoxia by mediating mitochondrial metabolism and consequently reducing oxidative stress. Recently, increased levels of oxidative stress and abnormal energy metabolism in the brain have been suggested to play essential roles in the pathogenesis of depression. Given that HIF-1 activates creatine metabolism and increases phosphocreatine levels in the intestinal epithelial cells, we assume that HIF-1 may induce similar processes in the brain. Elevated phosphocreatine levels in the brain, as measured by magnetic resonance spectroscopy, were associated with better treatment response to the antidepressants in individuals with depression. In addition, oral creatine supplements, which led to increased phosphocreatine levels in the brain, also enhanced the effects of antidepressants in individuals with depression. As such, we hypothesized that increasing the HIF-1, which potentially facilitates creatine metabolism in the brain, might be a new therapeutic target in depression. With this regard, we suggested that interventions to elevate the HIF-1 levels in the brain, including the intermittent hypoxia conditioning and hyperbaric oxygen therapy, might be considered as new additional treatments for depression.
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Affiliation(s)
- Ilhyang Kang
- Ewha Brain Institute, Ewha W. University, Seoul, South Korea
| | - Douglas Kondo
- Department of Psychiatry, University of Utah, Salt Lake City, USA; The Brian Institute, University of Utah School of Medicine, Salt Lake City, USA
| | - Jungyoon Kim
- Ewha Brain Institute, Ewha W. University, Seoul, South Korea; Department of Brain and Cognitive Sciences, Ewha W. University, Seoul, South Korea
| | - In Kyoon Lyoo
- Ewha Brain Institute, Ewha W. University, Seoul, South Korea; Department of Psychiatry, University of Utah, Salt Lake City, USA; The Brian Institute, University of Utah School of Medicine, Salt Lake City, USA
| | - Deborah Yurgelun-Todd
- Department of Psychiatry, University of Utah, Salt Lake City, USA; The Brian Institute, University of Utah School of Medicine, Salt Lake City, USA; Veterans Integrated Service Network 19 Mental Illness Research Education Clinical, Centers of Excellence, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah, USA
| | - Jaeuk Hwang
- Department of Psychiatry, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, South Korea.
| | - Perry F Renshaw
- Department of Psychiatry, University of Utah, Salt Lake City, USA; The Brian Institute, University of Utah School of Medicine, Salt Lake City, USA; Veterans Integrated Service Network 19 Mental Illness Research Education Clinical, Centers of Excellence, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
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31
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Hu K, Deng W, Yang J, Wei Y, Wen C, Li X, Chen Q, Ke D, Li G. Intermittent hypoxia reduces infarct size in rats with acute myocardial infarction: a systematic review and meta-analysis. BMC Cardiovasc Disord 2020; 20:422. [PMID: 32962654 PMCID: PMC7507284 DOI: 10.1186/s12872-020-01702-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 09/09/2020] [Indexed: 11/20/2022] Open
Abstract
Background To determine whether intermittent hypoxia (IH) can reduce the infarct size (IS) after acute myocardial infarction (AMI) in rats. Methods Articles were identified in PubMed, EMBASE and the Web of Science and were included if they evaluated the effect of IH on the changes in the infarcted area after AMI in rats. Results A preliminary search identified 3633 articles and 29 data sets from 23 articles (12 in vivo, 16 in vitro). The IS decreased after AMI in IH rats both in vitro (SMD -1.46, 95% CI [− 2.37, − 0.55]; I2 = 85.6%, P = 0.000) and in vivo (SMD -1.43, 95% CI [− 2.05, − 0.82], I2 = 73.6%, P = 0.000). Sensitivity analysis indicated that IH had a strong protective effect against myocardial infarction, and the hypoxia concentration was significantly correlated with the change in IS after AMI. Conclusion IH can reduce IS after AMI in rats. This effect of IH may be related to the dose of hypoxia, and the oxygen concentration may be one of the most important influencing factors.
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Affiliation(s)
- Ke Hu
- Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Wei Deng
- Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing, 400010, China.
| | - Jing Yang
- Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Yu Wei
- Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Chaolin Wen
- Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Xingsheng Li
- Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Qingwei Chen
- Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Dazhi Ke
- Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing, 400010, China
| | - Guiqiong Li
- Department of Geriatrics, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing, 400010, China
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Ryan S, Cummins EP, Farre R, Gileles-Hillel A, Jun JC, Oster H, Pepin JL, Ray DW, Reutrakul S, Sanchez-de-la-Torre M, Tamisier R, Almendros I. Understanding the pathophysiological mechanisms of cardiometabolic complications in obstructive sleep apnoea: towards personalised treatment approaches. Eur Respir J 2020; 56:13993003.02295-2019. [PMID: 32265303 DOI: 10.1183/13993003.02295-2019] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 03/15/2020] [Indexed: 12/19/2022]
Abstract
In January 2019, a European Respiratory Society research seminar entitled "Targeting the detrimental effects of sleep disturbances and disorders" was held in Dublin, Ireland. It provided the opportunity to critically review the current evidence of pathophysiological responses of sleep disturbances, such as sleep deprivation, sleep fragmentation or circadian misalignment and of abnormalities in physiological gases such as oxygen and carbon dioxide, which occur frequently in respiratory conditions during sleep. A specific emphasis of the seminar was placed on the evaluation of the current state of knowledge of the pathophysiology of cardiovascular and metabolic diseases in obstructive sleep apnoea (OSA). Identification of the detailed mechanisms of these processes is of major importance to the field and this seminar offered an ideal platform to exchange knowledge, and to discuss pitfalls of current models and the design of future collaborative studies. In addition, we debated the limitations of current treatment strategies for cardiometabolic complications in OSA and discussed potentially valuable alternative approaches.
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Affiliation(s)
- Silke Ryan
- Pulmonary and Sleep Disorders Unit, St Vincent's University Hospital, Dublin, Ireland .,School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland
| | - Eoin P Cummins
- School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland
| | - Ramon Farre
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona-IDIBAPS, and CIBER Enfermedades Respiratorias, Barcelona, Spain
| | - Alex Gileles-Hillel
- Pediatric Pulmonology and Sleep Unit, Dept of Pediatrics, and The Wohl Institute for Translational Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
| | - Jonathan C Jun
- Pulmonary and Critical Care Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
| | - Henrik Oster
- Institute of Neurobiology, University of Lübeck, Lübeck, Germany
| | | | - David W Ray
- NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.,Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
| | - Sirimon Reutrakul
- Division of Endocrinology, Diabetes, and Metabolism, Dept of Medicine, University of Illinois at Chicago, Chicago, IL, USA
| | - Manuel Sanchez-de-la-Torre
- Group of Precision Medicine in Chronic Diseases, Hospital Arnau de Vilanova-Santa Maria, IRBLleida, Lleida, Spain.,Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
| | - Renaud Tamisier
- HP2 INSERM U1042, Université Grenoble Alpes, Grenoble, France
| | - Isaac Almendros
- Unitat de Biofísica i Bioenginyeria, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona-IDIBAPS, and CIBER Enfermedades Respiratorias, Barcelona, Spain
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Packer M. Autophagy-dependent and -independent modulation of oxidative and organellar stress in the diabetic heart by glucose-lowering drugs. Cardiovasc Diabetol 2020; 19:62. [PMID: 32404204 PMCID: PMC7222526 DOI: 10.1186/s12933-020-01041-4] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 05/09/2020] [Indexed: 02/07/2023] Open
Abstract
Autophagy is a lysosome-dependent intracellular degradative pathway, which mediates the cellular adaptation to nutrient and oxygen depletion as well as to oxidative and endoplasmic reticulum stress. The molecular mechanisms that stimulate autophagy include the activation of energy deprivation sensors, sirtuin-1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK). These enzymes not only promote organellar integrity directly, but they also enhance autophagic flux, which leads to the removal of dysfunctional mitochondria and peroxisomes. Type 2 diabetes is characterized by suppression of SIRT1 and AMPK signaling as well as an impairment of autophagy; these derangements contribute to an increase in oxidative stress and the development of cardiomyopathy. Antihyperglycemic drugs that signal through insulin may further suppress autophagy and worsen heart failure. In contrast, metformin and SGLT2 inhibitors activate SIRT1 and/or AMPK and promote autophagic flux to varying degrees in cardiomyocytes, which may explain their benefits in experimental cardiomyopathy. However, metformin and SGLT2 inhibitors differ meaningfully in the molecular mechanisms that underlie their effects on the heart. Whereas metformin primarily acts as an agonist of AMPK, SGLT2 inhibitors induce a fasting-like state that is accompanied by ketogenesis, a biomarker of enhanced SIRT1 signaling. Preferential SIRT1 activation may also explain the ability of SGLT2 inhibitors to stimulate erythropoiesis and reduce uric acid (a biomarker of oxidative stress)—effects that are not seen with metformin. Changes in both hematocrit and serum urate are the most important predictors of the ability of SGLT2 inhibitors to reduce the risk of cardiovascular death and hospitalization for heart failure in large-scale trials. Metformin and SGLT2 inhibitors may also differ in their ability to mitigate diabetes-related increases in intracellular sodium concentration and its adverse effects on mitochondrial functional integrity. Differences in the actions of SGLT2 inhibitors and metformin may reflect the distinctive molecular pathways that explain differences in the cardioprotective effects of these drugs.
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Affiliation(s)
- Milton Packer
- Baylor Heart and Vascular Institute, Baylor University Medical Center, 621 N. Hall Street, Dallas, TX, 75226, USA. .,Imperial College, London, UK.
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Effects of Living High-Training Low and High on Body Composition and Metabolic Risk Markers in Overweight and Obese Females. BIOMED RESEARCH INTERNATIONAL 2020; 2020:3279710. [PMID: 32104687 PMCID: PMC7036094 DOI: 10.1155/2020/3279710] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Revised: 01/14/2020] [Accepted: 01/21/2020] [Indexed: 12/13/2022]
Abstract
This study examined the effects of 4 weeks of living high-training low and high (LHTLH) under moderate hypoxia on body weight, body composition, and metabolic risk markers of overweight and obese females. Nineteen healthy overweight or obese females participated in this study. Participants were assigned to the normoxic training group (NG) or the LHTLH group (HG). The NG participants lived and trained at sea level. The HG participants stayed for approximately 10 hours in a simulated 2300 m normobaric state of hypoxia for six days a week and trained for 2 hours 3 times a week under the same simulated hypoxia. The interventions lasted for 4 weeks. All groups underwent dietary restriction based on resting metabolic rate. The heart rate of the participants was monitored every ten minutes during exercise to ensure that the intensity was in the aerobic range. Compared with the preintervention values, body weight decreased significantly in both the NG and the HG (−8.81 ± 2.09% and −9.09 ± 1.15%, respectively). The fat mass of the arm, leg, trunk, and whole body showed significant reductions in both the NG and the HG, but no significant interaction effect was observed. The percentage of lean soft tissue mass loss in the total body weight loss tended to be lower in the HG (27.61% versus 15.94%, P=0.085). Between the NG and the HG, significant interaction effects of serum total cholesterol (−12.66 ± 9.09% versus −0.05 ± 13.36%,) and apolipoprotein A1 (−13.66 ± 3.61% versus −5.32 ± 11.07%, P=0.042) were observed. A slight increase in serum high-density lipoprotein cholesterol (HDL-C) was observed in the HG (1.12 ± 12.34%) but a decrease was observed in the NG (−11.36 ± 18.91%). The interaction effect of HDL-C between NG and HG exhibited a significant trend (P=0.055). No added effects on serum triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), or APO-B were observed after 4 weeks of LHTLH. In conclusion, 4 weeks of LHTLH combined with dietary restriction could effectively reduce the body weight and body fat mass of overweight and obese females. Compared with training and sleeping under normoxia, no additive benefit of LHTLH on the loss of body weight and body fat mass was exhibited. However, LHTLH may help to relieve the loss of lean soft tissue mass and serum HDL-C.
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Liu X, Chen X, Kline G, Ross SE, Hall JR, Ding Y, Mallet RT, Shi X. Reduced cerebrovascular and cardioventilatory responses to intermittent hypoxia in elderly. Respir Physiol Neurobiol 2020; 271:103306. [DOI: 10.1016/j.resp.2019.103306] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Revised: 09/08/2019] [Accepted: 09/22/2019] [Indexed: 11/26/2022]
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Wang H, Shi X, Schenck H, Hall JR, Ross SE, Kline GP, Chen S, Mallet RT, Chen P. Intermittent Hypoxia Training for Treating Mild Cognitive Impairment: A Pilot Study. Am J Alzheimers Dis Other Demen 2020; 35:1533317519896725. [PMID: 31902230 PMCID: PMC10624018 DOI: 10.1177/1533317519896725] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Although intermittent hypoxia training (IHT) has proven effective against various clinical disorders, its impact on mild cognitive impairment (MCI) is unknown. This pilot study examined IHT's safety and therapeutic efficacy in elderly patients with amnestic MCI (aMCI). Seven patients with aMCI (age 69 ± 3 years) alternately breathed 10% O2 and room-air, each 5 minutes, for 8 cycles/session, 3 sessions/wk for 8 weeks. The patients' resting arterial pressures fell by 5 to 7 mm Hg (P < .05) and cerebral tissue oxygenation increased (P < .05) following IHT. Intermittent hypoxia training enhanced hypoxemia-induced cerebral vasodilation (P < .05) and improved mini-mental state examination and digit span scores from 25.7 ± 0.4 to 27.7 ± 0.6 (P = .038) and from 24.7 ± 1.2 to 26.1 ± 1.3 (P = .047), respectively. California verbal learning test score tended to increase (P = .102), but trail making test-B and controlled oral word association test scores were unchanged. Adaptation to moderate IHT may enhance cerebral oxygenation and hypoxia-induced cerebrovasodilation while improving short-term memory and attention in elderly patients with aMCI.
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Affiliation(s)
- Hong Wang
- Departments of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA
- Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Xiangrong Shi
- Departments of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA
- Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - Hannah Schenck
- Departments of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - James R. Hall
- Departments of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA
- Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - Sarah E. Ross
- Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA
- Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - Geoffrey P. Kline
- Department of Internal Medicine, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - Shande Chen
- Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - Robert T. Mallet
- Departments of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - Peijie Chen
- Shanghai University of Sport, Shanghai, China
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Serebrovska TV, Grib ON, Portnichenko VI, Serebrovska ZO, Egorov E, Shatylo VB. Intermittent Hypoxia/Hyperoxia Versus Intermittent Hypoxia/Normoxia: Comparative Study in Prediabetes. High Alt Med Biol 2019; 20:383-391. [DOI: 10.1089/ham.2019.0053] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Affiliation(s)
| | - Oksana N. Grib
- D.F. Chebotarev State Institute of Gerontology, Kiev, Ukraine
| | | | | | - Egor Egorov
- CellAir Construction GmbH, Stuttgart, Germany
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Serebrovska ZO, Serebrovska TV, Kholin VA, Tumanovska LV, Shysh AM, Pashevin DA, Goncharov SV, Stroy D, Grib ON, Shatylo VB, Bachinskaya NY, Egorov E, Xi L, Dosenko VE. Intermittent Hypoxia-Hyperoxia Training Improves Cognitive Function and Decreases Circulating Biomarkers of Alzheimer's Disease in Patients with Mild Cognitive Impairment: A Pilot Study. Int J Mol Sci 2019; 20:E5405. [PMID: 31671598 PMCID: PMC6862463 DOI: 10.3390/ijms20215405] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 10/23/2019] [Accepted: 10/24/2019] [Indexed: 12/15/2022] Open
Abstract
Alzheimer's disease (AD) affects not only the central nervous system, but also peripheral blood cells including neutrophils and platelets, which actively participate in pathogenesis of AD through a vicious cycle between platelets aggregation and production of excessive amyloid beta (Aβ). Platelets adhesion on amyloid plaques also increases the risk of cerebral microcirculation disorders. Moreover, activated platelets release soluble adhesion molecules that cause migration, adhesion/activation of neutrophils and formation of neutrophil extracellular traps (NETs), which may damage blood brain barrier and destroy brain parenchyma. The present study examined the effects of intermittent hypoxic-hyperoxic training (IHHT) on elderly patients with mild cognitive impairment (MCI), a precursor of AD. Twenty-one participants (age 51-74 years) were divided into three groups: Healthy Control (n = 7), MCI+Sham (n = 6), and MCI+IHHT (n = 8). IHHT was carried out five times per week for three weeks (total 15 sessions). Each IHHT session consisted of four cycles of 5-min hypoxia (12% FIO2) and 3-min hyperoxia (33% FIO2). Cognitive parameters, Aβ and amyloid precursor protein (APP) expression, microRNA 29, and long non-coding RNA in isolated platelets as well as NETs in peripheral blood were investigated. We found an initial decline in cognitive function indices in both MCI+Sham and MCI+IHHT groups and significant correlations between cognitive test scores and the levels of circulating biomarkers of AD. Whereas sham training led to no change in these parameters, IHHT resulted in the improvement in cognitive test scores, along with significant increase in APP ratio and decrease in Aβ expression and NETs formation one day after the end of three-week IHHT. Such effects on Aβ expression and NETs formation remained more pronounced one month after IHHT. In conclusion, our results from this pilot study suggested a potential utility of IHHT as a new non-pharmacological therapy to improve cognitive function in pre-AD patients and slow down the development of AD.
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Affiliation(s)
- Zoya O Serebrovska
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, Kyiv 01024, Ukraine.
| | | | - Viktor A Kholin
- Department of Age Physiology and Pathology of Nervous System, Chebotarev Institute of Gerontology NAMS of Ukraine, Kyiv 04114, Ukraine.
| | - Lesya V Tumanovska
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, Kyiv 01024, Ukraine.
| | - Angela M Shysh
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, Kyiv 01024, Ukraine.
| | - Denis A Pashevin
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, Kyiv 01024, Ukraine.
| | - Sergii V Goncharov
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, Kyiv 01024, Ukraine.
| | - Dmytro Stroy
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, Kyiv 01024, Ukraine.
| | - Oksana N Grib
- Department of Clinical Physiology and Pathology of Internal Organs, Chebotarev Institute of Gerontology NAMS of Ukraine, Kyiv 04114, Ukraine.
| | - Valeriy B Shatylo
- Department of Clinical Physiology and Pathology of Internal Organs, Chebotarev Institute of Gerontology NAMS of Ukraine, Kyiv 04114, Ukraine.
| | - Natalia Yu Bachinskaya
- Department of Age Physiology and Pathology of Nervous System, Chebotarev Institute of Gerontology NAMS of Ukraine, Kyiv 04114, Ukraine.
| | - Egor Egorov
- CellAir Constructions GmbH, Schorndorf 73614, Germany.
| | - Lei Xi
- Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298-0204, USA.
| | - Victor E Dosenko
- Department of General and Molecular Pathophysiology, Bogomoletz Institute of Physiology, Kyiv 01024, Ukraine.
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Krueger K, Catanese L, Scholz H. Intermittent hypoxia: Friend and foe. Acta Physiol (Oxf) 2019; 226:e13276. [PMID: 30892796 DOI: 10.1111/apha.13276] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 03/15/2019] [Indexed: 12/18/2022]
Affiliation(s)
- Katharina Krueger
- Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Lorenzo Catanese
- Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Holger Scholz
- Institut für Vegetative Physiologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
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Intermittent normobaric hypoxia facilitates high altitude acclimatization by curtailing hypoxia-induced inflammation and dyslipidemia. Pflugers Arch 2019; 471:949-959. [DOI: 10.1007/s00424-019-02273-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 02/26/2019] [Accepted: 03/20/2019] [Indexed: 12/23/2022]
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Pierard M, Tassin A, Conotte S, Zouaoui Boudjeltia K, Legrand A. Sustained Intermittent Hypoxemia Induces Adiponectin Oligomers Redistribution and a Tissue-Specific Modulation of Adiponectin Receptor in Mice. Front Physiol 2019; 10:68. [PMID: 30800074 PMCID: PMC6376175 DOI: 10.3389/fphys.2019.00068] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 01/21/2019] [Indexed: 01/13/2023] Open
Abstract
Introduction: Hypoxemia is a critical component of several respiratory diseases and is known to be involved in the processes underlying co-morbidities associated to such disorders, notably at the cardiovascular level. Circulating level of Adiponectin (Ad), known as a metabolic regulator and cardio-protective hormone was previously suggested to be reduced by hypoxia but consequences of such variation are unclear. The evaluation of the specific effect of hypoxemia on Ad forms and receptors could improve the understanding of the involvement of Ad axis in hypoxemia-related diseases. Methods: Ad-pathway components were investigated in a murine model of sustained intermittent hypoxemia (FiO2 10%, 8 h/day, 35 days). Results: Sustained intermittent hypoxemia (SIH) induced a redistribution of Ad multimers in favor of HMW forms, without change in total plasmatic level. Mice submitted to hypoxia also exhibited tissue-specific modification of adiporeceptor (AdipoR) protein level without mRNA expression change. A decreased AdipoR2 abundance was observed in skeletal muscle and heart whereas AdipoR1 level was only reduced in muscle. No change was observed in liver regarding AdipoR. Lipid profile was unchanged but glucose tolerance increased in hypoxemic mice. Conclusion: Sustained intermittent hypoxemia, per se, modify Ad oligomerization state as well as AdipoR protein abundance in a tissue-specific way. That suggests alteration in Ad-dependant pathways in pathological conditions associated to SIH. Investigation of Ad-pathway components could therefore constitute useful complementary criteria for the clustering of patients with hypoxemia-related diseases and management of co-morbidities, as well as to develop new therapeutic strategies.
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Affiliation(s)
- Mélany Pierard
- Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium
| | - Alexandra Tassin
- Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium
| | - Stéphanie Conotte
- Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium
| | - Karim Zouaoui Boudjeltia
- Laboratory of Experimental Medicine (ULB 222), Medicine Faculty, CHU de Charleroi, Université Libre de Bruxelles, Brussels, Belgium
| | - Alexandre Legrand
- Laboratory of Respiratory Physiology, Pathophysiology and Rehabilitation, Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium
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Serebrovska TV, Portnychenko AG, Portnichenko VI, Xi L, Egorov E, Antoniuk-Shcheglova I, Naskalova S, Shatylo VB. 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; 119:813-823. [PMID: 30701312 DOI: 10.1007/s00421-019-04072-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 01/04/2019] [Indexed: 02/08/2023]
Abstract
PURPOSE Intermittent hypoxia training/treatment (IHT) is an emerging therapeutic approach to alleviate chronic diseases, such as diabetes. The present study investigated the effects of IHT on blood leucocyte pyruvate dehydrogenase kinase 1 (PDK-1) mRNA expression and its relationship with the changes in blood insulin level. METHODS Seven adult healthy volunteers and 11 prediabetic patients participated in this study. A 3-week course of IHT consisted of a 40-min session of 4 cycles of 5-min 12% O2 and 5-min room air breathing per day, 3 sessions per week for 3 weeks (i.e., total 9 sessions of IHT). Plasma insulin levels and leukocyte PDK-1 mRNA expression were determined at various time points either under fasting condition or following oral glucose tolerance test (OGTT). Correlation between the IHT-induced changes in PDK-1 mRNA and insulin or glucose levels in the same serological samples was analyzed. RESULTS At pre-IHT baseline, PDK-1 mRNA expression was two times higher in prediabetes than control subjects. IHT resulted in significant augmentation in PDK-1 mRNA expression (> twofold) in prediabetes at the end of 3-week IHT and remained elevated 1 month after IHT, which was correlated with a significantly reduced insulin release and lower blood glucose after glucose loading with OGTT. CONCLUSION IHT can trigger beneficial effects in normalizing blood insulin levels in prediabetic patients under oral glucose load, which were closely correlated with an enhanced mRNA expression of PDK-1 in leukocytes. Further clinical trials are warranted to validate the utility of IHT as a non-invasive complementary therapy against diabetes-associated pathologies.
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Affiliation(s)
| | - Alla G Portnychenko
- Bogomoletz Institute of Physiology, Kiev, 01024, Ukraine
- ICAMER, National Academy of Sciences of Ukraine, Kiev, 03680, Ukraine
| | - Vladimir I Portnichenko
- Bogomoletz Institute of Physiology, Kiev, 01024, Ukraine
- ICAMER, National Academy of Sciences of Ukraine, Kiev, 03680, Ukraine
| | - Lei Xi
- Pauley Heart Center, Department of Internal Medicine, Virginia Commonwealth University, 1101 East Marshall Street, Room 7-020C, Richmond, VA, 23298, USA.
- School of Sports Medicine and Health, Chengdu Sport University, Chengdu, 610041, China.
| | - Egor Egorov
- CELLGYM Technologies GmbH, 10623, Berlin, Germany
| | | | | | - Valeriy B Shatylo
- D.F. Chebotarev State Institute of Gerontology, Kiev, 04114, Ukraine
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Wang Y, Wen L, Zhou S, Zhang Y, Wang XH, He YY, Davie A, Broadbent S. Effects of four weeks intermittent hypoxia intervention on glucose homeostasis, insulin sensitivity, GLUT4 translocation, insulin receptor phosphorylation, and Akt activity in skeletal muscle of obese mice with type 2 diabetes. PLoS One 2018; 13:e0203551. [PMID: 30199540 PMCID: PMC6130870 DOI: 10.1371/journal.pone.0203551] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Accepted: 08/22/2018] [Indexed: 01/03/2023] Open
Abstract
AIMS The aims of this study were to determine the effects of four weeks of intermittent exposure to a moderate hypoxia environment (15% oxygen), and compare with the effects of exercise in normoxia or hypoxia, on glucose homeostasis, insulin sensitivity, GLUT4 translocation, insulin receptor phosphorylation, Akt-dependent GSK3 phosphorylation and Akt activity in skeletal muscle of obese mice with type 2 diabetes. METHODS C57BL/6J mice that developed type 2 diabetes with a high-fat-diet (55% fat) (fasting blood glucose, FBG = 13.9 ± 0.69 (SD) mmol/L) were randomly allocated into diabetic control (DC), rest in hypoxia (DH), exercise in normoxia (DE), and exercise in hypoxia (DHE) groups (n = 7, each), together with a normal-diet (4% fat) control group (NC, FBG = 9.1 ± 1.11 (SD) mmol/L). The exercise groups ran on a treadmill at intensities of 75-90% VO2max. The interventions were applied one hour per day, six days per week for four weeks. Venous blood samples were analysed for FBG, insulin (FBI) and insulin sensitivity (QUICKI) pre and post the intervention period. The quadriceps muscle samples were collected 72 hours post the last intervention session for analysis of GLUT4 translocation, insulin receptor phosphorylation, Akt expression and phosphorylated GSK3 fusion protein by western blot. Akt activity was determined by the ratio of the phosphorylated GSK3 fusion protein to the total Akt protein. RESULTS The FBG of the DH, DE and DHE groups returned to normal level (FBG = 9.4 ± 1.50, 8.86 ± 0.94 and 9.0 ± 1.13 (SD) mmol/L for DH, DE and DHE respectively, P < 0.05), with improved insulin sensitivity compared to DC (P < 0.05), after the four weeks treatment, while the NC and DC showed no significant changes, as analysed by general linear model with repeated measures. All three interventions resulted in a significant increase of GLUT4 translocation to cell membrane compared to the DC group (P < 0.05). The DE and DH showed a similar level of insulin receptor phosphorylation compared with NC that was significantly lower than the DC (P < 0.05) post intervention. The DH and DHE groups showed a significantly higher Akt activity compared to the DE, DC and NC (P < 0.05) post intervention, as analysed by one-way ANOVA. CONCLUSIONS This study produced new evidence that intermittent exposure to mild hypoxia (0.15 FiO2) for four weeks resulted in normalisation of FBG, improvement in whole body insulin sensitivity, and a significant increase of GLUT4 translocation in the skeletal muscle, that were similar to the effects of exercise intervention during the same time period, in mice with diet-induced type 2 diabetes. However, exercise in hypoxia for four weeks did not have additive effects on these responses. The outcomes of the research may contribute to the development of effective, alternative and complementary interventions for management of hyperglycaemia and type 2 diabetes, particularly for individuals with limitations in participation of physical activity.
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Affiliation(s)
- Yun Wang
- School of Health and Human Sciences, Southern Cross University, Lismore, Australia
| | - Li Wen
- Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport, Tianjin, China
| | - Shi Zhou
- School of Health and Human Sciences, Southern Cross University, Lismore, Australia
| | - Yong Zhang
- Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport, Tianjin, China
| | - Xin-Hao Wang
- Department of Health and Exercise Science, Tianjin University of Sport, Tianjin, China
| | - You-Yu He
- Department of Health and Exercise Science, Tianjin University of Sport, Tianjin, China
| | - Allan Davie
- School of Health and Human Sciences, Southern Cross University, Lismore, Australia
| | - Suzanne Broadbent
- School of Health and Human Sciences, Southern Cross University, Lismore, Australia
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Viscor G, Torrella JR, Corral L, Ricart A, Javierre C, Pages T, Ventura JL. Physiological and Biological Responses to Short-Term Intermittent Hypobaric Hypoxia Exposure: From Sports and Mountain Medicine to New Biomedical Applications. Front Physiol 2018; 9:814. [PMID: 30038574 PMCID: PMC6046402 DOI: 10.3389/fphys.2018.00814] [Citation(s) in RCA: 72] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 06/11/2018] [Indexed: 12/14/2022] Open
Abstract
In recent years, the altitude acclimatization responses elicited by short-term intermittent exposure to hypoxia have been subject to renewed attention. The main goal of short-term intermittent hypobaric hypoxia exposure programs was originally to improve the aerobic capacity of athletes or to accelerate the altitude acclimatization response in alpinists, since such programs induce an increase in erythrocyte mass. Several model programs of intermittent exposure to hypoxia have presented efficiency with respect to this goal, without any of the inconveniences or negative consequences associated with permanent stays at moderate or high altitudes. Artificial intermittent exposure to normobaric hypoxia systems have seen a rapid rise in popularity among recreational and professional athletes, not only due to their unbeatable cost/efficiency ratio, but also because they help prevent common inconveniences associated with high-altitude stays such as social isolation, nutritional limitations, and other minor health and comfort-related annoyances. Today, intermittent exposure to hypobaric hypoxia is known to elicit other physiological response types in several organs and body systems. These responses range from alterations in the ventilatory pattern to modulation of the mitochondrial function. The central role played by hypoxia-inducible factor (HIF) in activating a signaling molecular cascade after hypoxia exposure is well known. Among these targets, several growth factors that upregulate the capillary bed by inducing angiogenesis and promoting oxidative metabolism merit special attention. Applying intermittent hypobaric hypoxia to promote the action of some molecules, such as angiogenic factors, could improve repair and recovery in many tissue types. This article uses a comprehensive approach to examine data obtained in recent years. We consider evidence collected from different tissues, including myocardial capillarization, skeletal muscle fiber types and fiber size changes induced by intermittent hypoxia exposure, and discuss the evidence that points to beneficial interventions in applied fields such as sport science. Short-term intermittent hypoxia may not only be useful for healthy people, but could also be considered a promising tool to be applied, with due caution, to some pathophysiological states.
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Affiliation(s)
- Ginés Viscor
- Physiology Section, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
| | - Joan R. Torrella
- Physiology Section, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
| | - Luisa Corral
- Exercise Physiology Unit, Department of Physiological Sciences, Faculty of Medicine and Health Sciences, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Antoni Ricart
- Exercise Physiology Unit, Department of Physiological Sciences, Faculty of Medicine and Health Sciences, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Casimiro Javierre
- Exercise Physiology Unit, Department of Physiological Sciences, Faculty of Medicine and Health Sciences, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Teresa Pages
- Physiology Section, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain
| | - Josep L. Ventura
- Exercise Physiology Unit, Department of Physiological Sciences, Faculty of Medicine and Health Sciences, Universitat de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain
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Mallet RT, Manukhina EB, Ruelas SS, Caffrey JL, Downey HF. Cardioprotection by intermittent hypoxia conditioning: evidence, mechanisms, and therapeutic potential. Am J Physiol Heart Circ Physiol 2018; 315:H216-H232. [PMID: 29652543 DOI: 10.1152/ajpheart.00060.2018] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
The calibrated application of limited-duration, cyclic, moderately intense hypoxia-reoxygenation increases cardiac resistance to ischemia-reperfusion stress. These intermittent hypoxic conditioning (IHC) programs consistently produce striking reductions in myocardial infarction and ventricular tachyarrhythmias after coronary artery occlusion and reperfusion and, in many cases, improve contractile function and coronary blood flow. These IHC protocols are fundamentally different from those used to simulate sleep apnea, a recognized cardiovascular risk factor. In clinical studies, IHC improved exercise capacity and decreased arrhythmias in patients with coronary artery or pulmonary disease and produced robust, persistent, antihypertensive effects in patients with essential hypertension. The protection afforded by IHC develops gradually and depends on β-adrenergic, δ-opioidergic, and reactive oxygen-nitrogen signaling pathways that use protein kinases and adaptive transcription factors. In summary, adaptation to intermittent hypoxia offers a practical, largely unrecognized means of protecting myocardium from impending ischemia. The myocardial and perhaps broader systemic protection provided by IHC clearly merits further evaluation as a discrete intervention and as a potential complement to conventional pharmaceutical and surgical interventions.
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Affiliation(s)
- Robert T Mallet
- Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center , Fort Worth, Texas
| | - Eugenia B Manukhina
- Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center , Fort Worth, Texas.,Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences , Moscow , Russian Federation.,School of Medical Biology South Ural State University , Chelyabinsk , Russian Federation
| | - Steven Shea Ruelas
- Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center , Fort Worth, Texas
| | - James L Caffrey
- Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center , Fort Worth, Texas
| | - H Fred Downey
- Department of Integrative Physiology and Anatomy, University of North Texas Health Science Center , Fort Worth, Texas.,School of Medical Biology South Ural State University , Chelyabinsk , Russian Federation
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