Intermittent hypoxia (IH) improves hypoxic ventilatory sensitivity and blood dopamine (DA) in patients with Parkinson's disease (PD)

Serebrovskaya, Tatiana V.; Колесникова, Е. Э.; Karaban, I. N.; Mishunina, T. M.; Mankovskaya, I. N.; Safronova, O.S.

doi:10.1016/s0928-4680(98)81208-x

Cited by 5 publications

(7 citation statements)

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“…In part, these early findings led us to investigate IHT effects on the dopaminergic system. Healthy persons with low blood levels of dopamine and its precursor, dihydroxyphenylalanine, were found to have relatively large ventilatory responses to acute hypoxia (Serebrovskaya et al, 1996;Kolesnikova et al, 1999). In addition, and to follow up on the earlier work, particularly the concepts of Sirotinin, we performed studies to examine more specifically how IHT affected the autonomic nervous system in normal persons.…”

Section: Intermittent Hypoxic Training and The Autonomic Nervous Systemmentioning

confidence: 99%

Intermittent Hypoxia Research in the Former Soviet Union and the Commonwealth of Independent States: History and Review of the Concept and Selected Applications

Serebrovskaya

2002

High Altitude Medicine & Biology

123

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This review aims to summarize the basic research in the field of intermittent hypoxia in the Soviet Union and the Commonwealth of Independent States (CIS) that scientists in other Western countries may not be familiar with, since Soviet scientists were essentially cut off from the global scientific community for about 60 years. In the 1930s the concept of repeated hypoxic training was developed and the following induction methods were utilized: repeated stays at high-mountain camps for several weeks, regular high altitude flights by plane, training in altitude chambers, and training by inhalation of low-oxygen-gas mixtures. To the present day, intermittent hypoxic training (IHT) has been used extensively for altitude preacclimatization; for the treatment of a variety of clinical disorders, including chronic lung diseases, bronchial asthma, hypertension, diabetes mellitus, Parkinson's disease, emotional disorders, and radiation toxicity, in prophylaxis of certain occupational diseases; and in sports. The basic mechanisms underlying the beneficial effects of IHT are mainly in three areas: regulation of respiration, free-radical production, and mitochondrial respiration. It was found that IHT induces increased ventilatory sensitivity to hypoxia, as well as other hypoxia-related physiological changes, such as increased hematopoiesis, alveolar ventilation and lung diffusion capacity, and alterations in the autonomic nervous system. Due to IHT, antioxidant defense mechanisms are stimulated, cellular membranes become more stable, Ca(2+) elimination from the cytoplasm is increased, and O(2) transport in tissues is improved. IHT induces changes within mitochondria, involving NAD-dependent metabolism, that increase the efficiency of oxygen utilization in ATP production. These effects are mediated partly by NO-dependent reactions. The marked individual variability both in animals and humans in the response to, and tolerance of, hypoxia is described. Studies from the Soviet Union and the CIS significantly contributed to the understanding of intermittent hypoxia and its possible beneficial effects and should stimulate further research in this direction in other countries.

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Section: Intermittent Hypoxic Training and The Autonomic Nervous Systemmentioning

confidence: 99%

Intermittent Hypoxia Research in the Former Soviet Union and the Commonwealth of Independent States: History and Review of the Concept and Selected Applications

Serebrovskaya

2002

High Altitude Medicine & Biology

123

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“…Hypoxia-based therapy has been applied extensively in research in a wide spectrum of healthy participants and individuals with medical conditions, and both short- and long-term effects have been investigated. Examples of previously studied treatment goals in various populations include rehabilitation in spinal cord injury (SCI) [ 55 , 77 – 81 ], cardiorespiratory control in type I and II diabetes [ 82 , 83 ], endurance and exercise tolerance and performance in healthy and geriatric individuals [ 24 , 25 , 27 , 29 , 84 , 85 ], cognitive performance in geriatric and elderly individuals [ 22 , 26 , 28 , 86 ], cardiovascular risk factors in obese individuals [ 87 ], reducing acute mountain sickness [ 88 ], and training of respiratory dysfunction [ 42 , 48 , 89 – 91 ]. However, clinical parameters or symptomatic efficacy of hypoxia-based therapy have thus far never been studied in PD, even though the aforementioned underlying working mechanisms of hypoxia would make PD an attractive disorder to study.…”

Section: Discussionmentioning

confidence: 99%

“…However, clinical parameters or symptomatic efficacy of hypoxia-based therapy have thus far never been studied in PD, even though the aforementioned underlying working mechanisms of hypoxia would make PD an attractive disorder to study. One earlier brief report investigated the effects of (unspecified) IHT on the hypoxic ventilatory response in PD and found markedly reduced hypoxic ventilatory response, indicating a suboptimal response in breathing frequency to hypoxic challenges [ 48 ]. Because there is such limited previous experience with delivering hypoxia to persons with PD, several theoretical concerns must be addressed in this study proposed here.…”

Section: Discussionmentioning

confidence: 99%

“…Ventilation during the administration is expected to increase by ~ 20%, mostly due to increased tidal volume and less often due to respiratory rate [ 46 ]. Risk of unblinding due to these limited ventilatory effects is unlikely and has not been reported in previous hypoxic experiments [ 28 , 46 – 48 ]. Additionally, complaints of discomfort or shortness of breath are sometimes reported, regardless of the administered FiO2, indicating that this will not hamper blinding [ 23 – 25 ].…”

Section: Methodsmentioning

confidence: 99%

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Multiple N-of-1 trials to investigate hypoxia therapy in Parkinson’s disease: study rationale and protocol

Daalen

Meinders

Giardina³

et al. 2022

BMC Neurol

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Background Parkinson’s disease (PD) is a neurodegenerative disease, for which no disease-modifying therapies exist. Preclinical and clinical evidence suggest that hypoxia-based therapy might have short- and long-term benefits in PD. We present the contours of the first study to assess the safety, feasibility and physiological and symptomatic impact of hypoxia-based therapy in individuals with PD. Methods/Design In 20 individuals with PD, we will investigate the safety, tolerability and short-term symptomatic efficacy of continuous and intermittent hypoxia using individual, double-blind, randomized placebo-controlled N-of-1 trials. This design allows for dose finding and for including more individualized outcomes, as each individual serves as its own control. A wide range of exploratory outcomes is deployed, including the Movement Disorders Society Unified Parkinson’s Disease Rating scale (MDS-UPDRS) part III, Timed Up & Go Test, Mini Balance Evaluation Systems (MiniBES) test and wrist accelerometry. Also, self-reported impression of overall symptoms, motor and non-motor symptoms and urge to take dopaminergic medication will be assessed on a 10-point Likert scale. As part of a hypothesis-generating part of the study, we also deploy several exploratory outcomes to probe possible underlying mechanisms of action, including cortisol, erythropoietin and platelet-derived growth factor β. Efficacy will be assessed primarily by a Bayesian analysis. Discussion This evaluation of hypoxia therapy could provide insight in novel pathways that may be pursued for PD treatment. This trial also serves as a proof of concept for deploying an N-of-1 design and for including individualized outcomes in PD research, as a basis for personalized treatment approaches. Trial registration ClinicalTrials.gov Identifier: NCT05214287 (registered January 28, 2022).

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“…Hypoxic conditioning induces adaptive plasticity in the central and peripheral respiratory motor network, meaning that hypoxia remodels neuronal networks and thereby improves breathing function. 21,[96][97][98][99][100][101][102][103][104] One such study has been conducted in PD and demonstrated improved ventilatory responses to hypoxia. 105 This could be a novel addition to respiratory function training in PD, as complications of respiratory dysfunction are associated with high mortality.…”

Section: Adaptive Plasticitymentioning

confidence: 99%

The Hypoxia Response Pathway: A Potential Intervention Target in Parkinson's Disease?

Janssen Daalen,

Koopman,

Saris

et al. 2023

Movement Disorders

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Parkinson's disease (PD) is a progressive neurodegenerative disorder for which only symptomatic treatments are available. Both preclinical and clinical studies suggest that moderate hypoxia induces evolutionarily conserved adaptive mechanisms that enhance neuronal viability and survival. Therefore, targeting the hypoxia response pathway might provide neuroprotection by ameliorating the deleterious effects of mitochondrial dysfunction and oxidative stress, which underlie neurodegeneration in PD. Here, we review experimental studies regarding the link between PD pathophysiology and neurophysiological adaptations to hypoxia. We highlight the mechanistic differences between the rescuing effects of chronic hypoxia in neurodegeneration and short‐term moderate hypoxia to improve neuronal resilience, termed “hypoxic conditioning”. Moreover, we interpret these preclinical observations regarding the pharmacological targeting of the hypoxia response pathway. Finally, we discuss controversies with respect to the differential effects of hypoxia response pathway activation across the PD spectrum, as well as intervention dosing in hypoxic conditioning and potential harmful effects of such interventions. We recommend that initial clinical studies in PD should focus on the safety, physiological responses, and mechanisms of hypoxic conditioning, as well as on repurposing of existing pharmacological compounds. © 2023 International Parkinson and Movement Disorder Society.

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Intermittent hypoxia (IH) improves hypoxic ventilatory sensitivity and blood dopamine (DA) in patients with Parkinson's disease (PD)

Cited by 5 publications

References 0 publications

Intermittent Hypoxia Research in the Former Soviet Union and the Commonwealth of Independent States: History and Review of the Concept and Selected Applications

Intermittent Hypoxia Research in the Former Soviet Union and the Commonwealth of Independent States: History and Review of the Concept and Selected Applications

Multiple N-of-1 trials to investigate hypoxia therapy in Parkinson’s disease: study rationale and protocol

The Hypoxia Response Pathway: A Potential Intervention Target in Parkinson's Disease?

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