Physiological and Biological Responses to Short-Term Intermittent Hypobaric Hypoxia Exposure: From Sports and Mountain Medicine to New Biomedical Applications

In 1995 the American College of Sports Medicine and the Centers for Disease Control and Prevention published national guidelines on Physical Activity and Public Health. The Committee on Exercise and Cardiac Rehabilitation of the American Heart Association endorsed and supported these recommendations. The purpose of the present report is to update and clarify the 1995 recommendations on the types and amounts of physical activity needed by healthy adults to improve and maintain health. Development of this document was by an expert panel of scientists, including physicians, epidemiologists, exercise scientists, and public health specialists. This panel reviewed advances in pertinent physiologic, epidemiologic, and clinical scientific data, including primary research articles and reviews published since the original recommendation was issued in 1995. Issues considered by the panel included new scientific evidence relating physical activity to health, physical activity recommendations by various organizations in the interim, and communications issues. Key points related to updating the physical activity recommendation were outlined and writing groups were formed. A draft manuscript was prepared and circulated for review to the expert panel as well as to outside experts. Comments were integrated into the final recommendation. To promote and maintain health, all healthy adults aged 18 to 65 yr need moderate-intensity aerobic (endurance) physical activity for a minimum of 30 min on five days each week or vigorous-intensity aerobic physical activity for a minimum of 20 min on three days each week. [I (A)] Combinations of moderate- and vigorous-intensity activity can be performed to meet this recommendation. [IIa (B)] For example, a person can meet the recommendation by walking briskly for 30 min twice during the week and then jogging for 20 min on two other days. Moderate-intensity aerobic activity, which is generally equivalent to a brisk walk and noticeably accelerates the heart rate, can be accumulated toward the 30-min minimum by performing bouts each lasting 10 or more minutes. [I (B)] Vigorous-intensity activity is exemplified by jogging, and causes rapid breathing and a substantial increase in heart rate. In addition, every adult should perform activities that maintain or increase muscular strength and endurance a minimum of two days each week. [IIa (A)] Because of the dose-response relation between physical activity and health, persons who wish to further improve their personal fitness, reduce their risk for chronic diseases and disabilities or prevent unhealthy weight gain may benefit by exceeding the minimum recommended amounts of physical activity. [I (A)]

The cardiovascular system ensures the delivery of oxygen and nutrients to all cells, tissues, and organs. Under extended exposure to reduced oxygen levels, cells are able to survive through the transcriptional activation of a series of genes that participate in angiogenesis, glucose metabolism, and cell proliferation. The oxygen-sensitive transcriptional activator HIF-1 (hypoxia-inducible factor-1) is a key transcriptional mediator of the response to hypoxic conditions. The HIF-1 pathway was found to be a master regulator of angiogenesis. Whether the process is physiological or pathological, HIF-1 seems to participate in vasculature formation by synergistic correlations with other proangiogenic factors such as VEGF (vascular endothelial growth factor), PlGF (placental growth factor), or angiopoietins. Considering the important contributions of HIF-1 in angiogenesis and vasculogenesis, it should be considered a promising target for treating ischaemic diseases or cancer. In this review, we discuss the roles of HIF-1 in both physiological/pathophysiological angiogenesis and potential strategies for clinical therapy.

Intermittent hypoxia (IH) has been the subject of considerable research in recent years, and triggers a bewildering array of both detrimental and beneficial effects in multiple physiological systems. Here, we review the extensive literature concerning IH and its impact on the respiratory, cardiovascular, immune, metabolic, bone, and nervous systems. One major goal is to define relevant IH characteristics leading to safe, protective, and/or therapeutic effects vs. pathogenesis. To understand the impact of IH, it is essential to define critical characteristics of the IH protocol under investigation, including potentially the severity of hypoxia within episodes, the duration of hypoxic episodes, the number of hypoxic episodes per day, the pattern of presentation across time (e.g., within vs. consecutive vs. alternating days), and the cumulative time of exposure. Not surprisingly, severe/chronic IH protocols tend to be pathogenic, whereas any beneficial effects are more likely to arise from modest/acute IH exposures. Features of the IH protocol most highly associated with beneficial vs. pathogenic outcomes include the level of hypoxemia within episodes and the number of episodes per day. Modest hypoxia (9-16% inspired O2) and low cycle numbers (3-15 episodes per day) most often lead to beneficial effects without pathology, whereas severe hypoxia (2-8% inspired O2) and more episodes per day (48-2,400 episodes/day) elicit progressively greater pathology. Accumulating evidence suggests that "low dose" IH (modest hypoxia, few episodes) may be a simple, safe, and effective treatment with considerable therapeutic potential for multiple clinical disorders. Copyright © 2014 the American Physiological Society.