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Recently, endurance athletes and high altitude climbers have gained access to commercially available, portable normobaric hypoxic chambers. Intermittent exposures to hypoxia in these chambers may elicit adaptations similar to those observed during acclimatization to altitude. Manufactures of these systems purport that intermittent exposures may elicit adaptations similar to those observed in response to the hypoxia of high altitude, however there have been no reports in the scientific literature that ventilatory acclimatization or alterations in cerebrovascular dynamics occur following repeated episodes in the portable chambers. The main conclusions are that an intermittent normobaric hypoxic intervention, consisting of five consecutive overnight exposures to a simulated altitude of 4300m, elicits perturbations in the acute cerebrovascular and ventilatory responses to both hypoxia and hypercapnia, which are similar to changes following chronic altitude exposure. Individual variability to intermittent hypoxia may have an impact on the rate at which the process of acclimatization proceeds. The extent of physiological and symptomatic responses to intermittent hypoxia are likely to be associated with the severity of hypoxia as well as the length and number of recurrent episodes of hypoxia.
The appearance of photosynthetic organisms about 3 billion years ago increased the partial pressure of oxygen (PO2) in the atmosphere and enabled the evolution of organisms that use glucose and oxygen to produce ATP by oxidative phosphorylation. Hypoxia is commonly defined as the reduced availability of oxygen in the tissues produced by different causes, which include reduction of atmospheric PO2 as in high altitude, and secondary to pathological conditions such as sleep breathing and pulmonary disorders, anemia, and cardiovascular alterations leading to inadequate transport, delivery, and exchange of oxygen between capillaries and cells. Nowadays, it has been shown that hypoxia plays an important role in the genesis of several human pathologies including cardiovascular, renal, myocardial and cerebral diseases in fetal, young and adult life. Several mechanisms have evolved to maintain oxygen homeostasis. Certainly, all cells respond and adapt to hypoxia, but only a few of them can detect hypoxia and initiate a cascade of signals intended to produce a functional systemic response. In mammals, oxygen detection mechanisms have been extensively studied in erythropoietin-producing cells, chromaffin cells, bulbar and cortical neurons, pulmonary neuroepithelial cells, smooth muscle cells of pulmonary arteries, and chemoreceptor cells. While the precise mechanism underpinning oxygen, sensing is not completely known several molecular entities have been proposed as possible oxygen sensors (i.e. Hem proteins, ion channels, NADPH oxidase, mitochondrial cytochrome oxidase). Remarkably, cellular adaptation to hypoxia is mediated by the master oxygen-sensitive transcription factor, hypoxia-inducible factor-1, which can induce up-regulation of different genes to cope the cellular effects related to a decrease in oxygen levels. Short-term responses to hypoxia included mainly chemoreceptor-mediated reflex ventilatory and hemodynamic adaptations to manage the low oxygen concentration while more prolonged exposures to hypoxia can elicit more sustained physiological responses including switch from aerobic to anaerobic metabolism, vascularization, and enhancement of blood O2 carrying capacity. The focus of this research topic is to provide an up-to-date vision on the current knowledge on oxygen sensing mechanism, physiological responses to acute or chronic hypoxia and cellular/tissue/organ adaptations to hypoxic environment.
Intermittent hypoxia can cause significant structural and functional impact on the systemic, organic, cellular and molecular processes of human physiology and pathophysiology. This book focuses on the most updated scientific understanding of the adaptive (beneficial) and maladaptive (detrimental) responses to intermittent hypoxia and their potential pathogenetic or prophylactic roles in the development and progression of major human diseases. This is a comprehensive monograph for clinicians, research scientists, academic faculty, postgraduate and medical students, and allied health professionals who are interested in enhancing their up-to-date knowledge of intermittent hypoxia research and its translational applications in preventing and treating major human diseases.
In consolidation of the most updated experimental results and perspectives from diverse research fields on a main theme - Intermittent Hypoxia, this book encompasses the structural, physiological, pathophysiological, biochemical, genetic, metabolic, and therapeutic aspects of intermittent hypoxia and provides an open forum to promote the bench-to-bed translational implications of both adaptive (beneficial) and maladaptive (detrimental) responses to intermittent hypoxia in animals and humans. Authored by 74 leading scientists from 17 countries in Asia, Europe, North America, and Oceana, the 30 chapters are grouped under 7 different sections covering the profound effects of intermittent hypoxia particularly on cardiovascular, respiratory, nervous, and skeletal muscular systems. Special attentions are paid to the protective or injurious roles played by intermittent hypoxia and their underlying cellular and molecular mechanisms in several major human diseases such as acute myocardial infarction, stroke, sleep apnea, and Parkinsons disease. Several chapters have also reviewed the use of intermittent hypoxia training for enhancing exercise performance in elite athletes. Overall, as endorsed by Professor John B. West (Member, Institute of Medicine, National Academy of Sciences of U.S.A.; Editor-in-Chief, High Altitude Medicine and Biology) through his Foreword for the book, this is the most comprehensive monograph to date on the topic of intermittent hypoxia, which can cause significant structural and functional impact on the systemic, organic, cellular and molecular processes of human physiology and pathophysiology. Hence, this book could serve as a thorough reference for research scientists, physicians, academic faculty, graduate and medical students, athletic coaches and trainers, who are interested in enhancing their knowledge about the past, present, and future of intermittent hypoxia research and its translational applications for prevention and treatment of major diseases and improving exercise performance.
Hypoxia remains a constant threat throughout life. It is for this reason that the International Hypoxia Society strives to maintain a near quarter century tradition of presenting a stimulating blend of clinical and basic science discussions. International experts from many fields have focused on the state-of-the-art discoveries in normal and pathophysiological responses to hypoxia. Topics in this volume include gene-environment interactions, a theme developed in both a clinical context regarding exercise and hypoxia, as well as in native populations living in high altitudes. Furthermore, experts in the field have combined topics such as skeletal muscle angiogenesis and hypoxia, high altitude pulmonary edema, new insights into the biology of the erythropoietin receptor, and the latest advances in cardiorespiratory control in hypoxia. This volume explores the fields of anatomy, cardiology, biological transport, and biomedical engineering among many others.
Just one of a series of volumes on differing aspects of hypoxia, this authoritative text focuses on cutting-edge research at the interface of hypoxia and biomedicine. Hypoxia – or lack of oxygen – is a constant threat to the human body and its vital organs, one that can take its toll in a number of situations. There are many situations in which the threat is heightened in health and disease, but mechanisms have evolved to lessen its detrimental effects. The International Hypoxia Symposia was founded to enable scientists, clinicians, physiologists, immunologists, mountaineers and other interested individuals to share their experiences of the situations associated with the lack of oxygen and the adaptations that allow us to survive.
While severe hypoxia has detrimental health consequences, the controlled application of hypoxia can be protective and holds great promise as a performance-enhancing and therapeutic intervention. Hypoxia Conditioning in Health, Exercise and Sport: Principles, Mechanisms and Applications delivers an understanding of systemic and molecular mechanisms involved in hypoxia adaptations and examines the most promising forms of hypoxia conditioning with a view to create performance-enhancing strategies for athletes, as well as an offering an examination on clinical applications for numerous pathologies. This cutting-edge book examines how positive physiological adaptations not only acutely enhance tolerance to hypoxia but can also induce sustained health benefits. This has enabled the development and refinement of approaches utilizing hypoxia, strategies also termed hypoxia conditioning, to improve health and performance outcomes. By linking research with recommendations for real-world situations, this volume will serve as an invaluable resource for students, academics, exercise science professionals and sports medicine specialists, especially those in environmental physiology and coaching subjects.
The latest in a series of books from the International Hypoxia Symposia, this volume spans reviews on key topics in hypoxia, and abstracts from poster and oral presentations. The biannual International Hypoxia Symposia are dedicated to hosting the best basic scientific and clinical minds to focus on the integrative and translational biology of hypoxia. Long before ‘translational medicine’ was a catchphrase, the founders of the International Hypoxia Symposia brought together basic scientists, clinicians and physiologists to live, eat, ski, innovate and collaborate in the Canadian Rockies. This collection of reviews and abstracts is divided into six sections, each covering new and important work relevant to a broad range of researchers interested in how humans adjust to hypoxia, whether on the top of Mt. Everest or in the pulmonary or cardiology clinic at low altitude. The sections include: Epigenetic Variations in Hypoxia High Altitude Adaptation Hypoxia and Sleep Hypoxia and the Brain Molecular Oxygen Sensing Physiological Responses to Hypoxia
Obstructive sleep apnea (OSA) is an increasingly prevalent health problem, leading to periods of intermittent hypoxia (IH) during sleep. IH was used to model severe OSA in mice for my studies (15 cycles/h, 8 h/day, FIO2 nadir of 5%). OSA and dim light at night (dLAN) have both been independently associated with alterations in mood and cognition. In Chapter 2, I aimed to determine whether dLAN would interact with IH, to alter behavioral, cognitive, and affective responses. Adult male mice were housed in either standard lighting conditions (14:10; 150 lux:0 lux) or dLAN (150 lux:5 lux), and then were then exposed to IH for 3 weeks. The combination of IH and dLAN provokes negative effects on affect and cognition and reduced neuronal cell body area in the CA1 and 3 of the hippocampus. Prior studies have demonstrated both protective and harmful consequences of IH exposure prior to middle cerebral artery occlusion (MCAO); Chapter 3 extends this research by examining the effects of timing of IH on stroke-related neuronal death and neuroinflammation. The effects of ischemic outcome were dependent on duration of the IH exposure prior to MCAO; there was a significant reduction in stroke-induced infarct size after 11 days of IH exposure and 3 days of Air exposure following MCAO relative to Air/Air exposure. Likewise, interleukin (IL)-6 mRNA expression in the ipsilateral hemisphere was significantly reduced among mice exposed to 11 days of IH/Air relative to Air/Air mice. However, the protective effects of IH were no longer apparent among mice exposed to 20 days of IH prior to MCAO. Together, these data suggest that the protective effects of acute IH may be associated with reduced post-stroke proinflammatory cytokine expression; additionally, IH loses its protective quality following chronic exposure, such as might be experienced by people with obstructive sleep apnea. OSA occurs more frequently in postmenopausal than premenopausal women and the severity of OSA increase after menopause. Gonadal hormones can influence brain and behavior; testosterone and estrogens in particular can enhance spatial learning and memory. In Chapter 4, I hypothesized that estrogens may protect mice from IH-induced hippocampal morphological and behavioral changes. I exposed intact or gonadectomized male and female mice to room air or IH for 30 days. Ovariectomy paired with IH treatment, impaired spatial learning and memory compared to all other female groups. Intact male mice exposed to IH impaired learning and memory compared to male mice exposed to room air. Learning and memory changes in female mice were mirrored by changes in basilar dendritic length of the CA1 region of the hippocampus. In Chapter 5, I examined the effects of dihydrotestosterone (DHT), a non-aromatizable androgen, on learning and memory performance in female mice. Ovariectomized mice with DHT capsules were protected from IH-induced spatial learning and memory deficits following 30 days of treatment. IH combined with other factors like, light at night and hormone removal produce behavior more consistent with OSA symptoms. When assessing individuals with OSA it is important to consider their environment, age, sex, and hormonal status.