Physiological effects of intermittent hypoxia

Intermittent hypoxia (IH), or periodic exposure to hypoxia interrupted by return to normoxia or less hypoxic conditions, occurs in many circumstances. In high altitude mountaineering, IH is used to optimize acclimatization although laboratory studies have not generally revealed physiologically significant benefits. IH enhances athletic performance at sea level if blood oxygen capacity increases and the usual level of training is not decreased significantly. IH for high altitude workers who commute from low altitude homes is of considerable practical interest and the ideal commuting schedule for physical and mental performance is being studied. The effect of oxygen enrichment at altitude (i.e., intermittent normoxia on a background of chronic hypoxia) on human performance is under study also. Physiological mechanisms of IH, and specifically the differences between effects of IH and acute or chronic continuous hypoxia remains to be determined. Biomedical researchers are defining the molecular and cellular mechanisms for effects of hypoxia on the body in health and disease. A comparative approach may provide additional insight about the biological significance of these effects.     

The effect of intermittent normobaric hypoxia on oxygen metabolism in hypertonic pilots]

Oxygen tissue metabolism was evaluated in hypertonic pilots in order to draw up an optimal treatment plan. Oxygen metabolism kinetics was determined with the help of transcutaneous polarography and the local ischemic extremity test was applied to measure the O2 utilization efficiency. Breathing mixture of 90% nitrogen and 10% oxygen (GGS-10) was used in therapeutic sessions of intermittent normobaric hypoxia. Results point to the reduced tissue breathing intensity and cell functional energy reserve in hypertonic patients. However, O2 metabolism is much closer to normal in pilots as compared with non-flyers. In pilots, O2 utilization is more intensive, energy supply of cells is higher, O2 transport and utilization are well-balanced, and tissue breathing is less reactive to the hypoxic factor. Dynamic kinetics of O2 metabolism tested post treatment suggested activation of O2 tissue metabolism in the hypertonic pilots rather than O2 transport which was stimulated in non-flyers. In addition, by the end of treatment the pilots were advised to extend the period of breathing GGS-10 leaving the period of air breathing unchanged. Consequently, the pilots were more adaptable to hypoxia than the non-flyers and, therefore, improved O2 tissue metabolism more rapidly.     

Unchanged anaerobic and aerobic performance after short-term intermittent hypoxia

INTRODUCTION: Repeated short-term exposures to a severe degree of hypoxia, alternated with similar intervals of normoxia, are recommended for performance enhancement in sports. However, scientific evidence for the efficiency of this method is controversial with regard to anaerobic performance. Therefore, we conducted a randomized, double-blind, placebo-controlled study to investigate the effects of this new method on both anaerobic and aerobic performance. METHODS: During 15 consecutive days, 20 endurance-trained men (V O2max (mean +/- SD) 60.2 +/- 6.8 mL x kg(-1) x min(-1)) were exposed each day to breathing (through mouthpieces) either a gas mixture (11% O2 on days 1-7 and 10% O2 on days 8-15; hypoxia group, N = 10) or compressed air (control group, N = 10), six times for 6 min, followed by 4 min of breathing room air for a total of six consecutive cycles. Before and after the treatment, an incremental cycle ergometer test to exhaustion and the Wingate anaerobic test were performed to assess aerobic and anaerobic performance. RESULTS: Hypoxic treatment did not improve peak power or mean power during the Wingate anaerobic test, nor did it affect maximal oxygen uptake (V O2max), maximal power output (Pmax), lactate threshold or levels of heart rate (HR), minute ventilation (V E), oxygen uptake (V O2), or blood lactate concentration at the submaximal workloads during the ergometer test. Maximal lactate concentration (Lamax) after the tests and HRmax and maximal respiratory exchange ratio (RERmax) during the ergometer test were not significantly different between groups at any time. CONCLUSION: The results of this study demonstrated that 1 h of intermittent hypoxic exposure for 15 consecutive days has no effect on aerobic or anaerobic performance.     

Cell inactivation by combined low dose-rate irradiation and intermittent hypoxia

Abstract

Purpose: To investigate in detail the earlier observed combined effect of low dose-rate β-irradiation delivered at a dose-rate of 15 mGy/h and continued intermittent hypoxia that leads to extensive cell death after approximately 3–6 weeks.

Material and methods: Continuous low dose-rate β-irradiation at a dose rate of 15, 1.5 or 0.6 mGy/h was given by incorporation of [³H]-labelled valine into cellular protein. The cells were cultivated in an atmosphere with 4% O₂ using an INVIVO₂ hypoxia glove box. Clonogenic capacity, cell-cycle distribution and cellular respiration were monitored throughout the experiments.

Results: After 3–6 weeks most cells died in response to the combined treatment, giving a surviving fraction of only 1–2%. However, on continued cultivation a few cells survived and restarted proliferation as the cellular oxygen supply increased with the reduced cell number. Irradiating the T-47D cells grown in an atmosphere with 4% O₂ at dose-rates 10 and 25 times lower than 15 mGy/h did not have a pronounced effect on the clonogenic capacity with surviving fractions of 60–80%.

Conclusions: Treatment of T-47D cells with low dose-rate β-irradiation leads to a specific effect on intermittent hypoxic cells, inactivating more than 98% of the cells in the population. Given improved oxygen conditions, the few surviving cells can restart their proliferation.     

Effect of short-term and intermittent normobaric hypoxia on endogenous erythropoietin isoforms

The aim of the present study was to evaluate whether the Epo isoforms in blood, induced by short-term and intermittent hypoxia, are different from those at normoxia at sea level and if this could be an impediment to the use of a direct Epo doping test based upon the electric charge of the Epo isoforms. Ten healthy subjects, 9 men and 1 woman, participated in the study. Median age was 22 years (range 20-32). Normobaric hypoxia was administered differently in 3 sub-groups; two groups with 12 h hypoxia and 12 h normoxia up to 10 days: IM 2000 and IM 2700 living in 16.2% and 14.9% O2, corresponding to 2000 and 2700 m above sea level, respectively, and training in normoxia. The third group, C 2700, lived in hypoxia, 14.9% O2 corresponding to 2700 m, continuously for 48 h. The mean serum Epo level increased from 10.9 IUL(-1) (range 8.8-12.5) to 23.5 IUL(-1) (15.6-29.1) after 2 days followed by 19.7 IUL(-1) (16.1-24.1) after 10 days exposure for intermittent hypoxia. The highest values 39.5 IUL(-1) (31.5-50) were obtained for the group exposed for continuous hypoxia for 48 h. The median electrophoretic mobility of the serum Epo isoforms was above the cut-off limit of 670 AMU, previously estimated for discrimination between recombinant and endogenous Epo, in all samples taken before and after exposure to hypoxia. The highest values, mean 730 mAMU (range 703-750) were obtained after 10 days of intermittent hypoxia. CONCLUSION: If the method had been used as a doping test, no false positive results would have been registered for the 15 serum samples from the 10 individuals exposed for hypoxia. Thus, the results indicate that the basic principle for direct detection of recombinant Epo doping, based upon the change in electric charge on Epo, can be used also on individuals having lived in a hypoxic milieu.     

Effects of intermittent hypoxia on heart rate variability during rest and exercise

Changes in heart rate variability induced by an intermittent exposure to hypoxia were evaluated in athletes unacclimatized to altitude. Twenty national elite athletes trained for 13 days at 1200 m and either lived and slept at 1200 m (live low, train low, LLTL) or between 2500 and 3000 m (live high, train low, LHTL). Subjects were investigated at 1200 m prior to and at the end of the 13-day training camp. Exposure to acute hypoxia (11.5% O(2)) during exercise resulted in a significant decrease in spectral components of heart rate variability in comparison with exercise in normoxia: total power (p < 0.001), low-frequency component. LF (p < 0.001), high-frequency component, HF (p < 0.05). Following acclimatization, the LHTL group increased its LF component (p < 0.01) and LF/HF ratio during exercise in hypoxia after the training period. In parallel, exposure to intermittent hypoxia caused an increased ventilatory response to hypoxia. Acclimatization modified the correlation between the ventilatory response to hypoxia at rest and the difference in total power between normoxia and hypoxia (r (2) = 0.65, p < 0.001). The increase in total power, LF component, and LF/HF ratio suggests that intermittent hypoxic training increased the response of the autonomic nervous system mainly through increased sympathetic activity.     

Short‐term intermittent hypoxia reduces the severity of acute mountain sickness

Intermittent hypoxia (IH) is a promising approach to induce acclimatization and hence lower the risk of developing acute mountain sickness (AMS). We hypothesized that a short‐term IH protocol in normobaric hypoxia (7 × 1 h to 4500 m) effectively increases the hypoxic ventilatory response (HVR) and reduces the incidence and severity of AMS. Therefore, 26 men (25.5 ± 4.4 years), assigned in a double‐blinded fashion to the hypoxia group (HG) or placebo group (PG), spent 8 h at 5300 m before (PRE) and 2 days after cessation of the IH protocol (POST). Measurements included the evaluation of the Lake Louise Score (LLS) and the HVR. The severity of AMS decreased from PRE to POST in the HG (from 6.0 ± 2.7 at PRE to 4.1 ± 2.1 at POST), whereas the LLS in the PG stayed high (from 5.7 ± 2.9 to 5.5 ± 2.8, respectively). The HVR in the HG increased from 0.73 ± 0.4 L/min/% at PRE to 1.10 ± 0.5 L/min/% at POST and did not increase in the PG. The reduction of the LLS was inversely related to the changes in the HVR (r = ?0.434), but the AMS incidence was not different between the HG and the PG at POST. In conclusion, short‐term IH reduced the severity of AMS development during a subsequent 8‐h exposure to normobaric hypoxia.     

Improvement of myocardial perfusion in coronary patients after intermittent hypobaric hypoxia

BACKGROUND: Persons living at high altitude (exposed to hypoxia) have a greater number of coronary and peripheral branches in the heart than persons living at sea level. In this study we investigated the effect of intermittent hypobaric hypoxia on myocardial perfusion in patients with coronary heart disease. METHODS AND RESULTS: We studied 6 male patients (aged>or=53 years) with severe stable coronary heart disease. All patients were born at sea level and lived in that environment. They underwent 14 sessions of exposure to intermittent hypobaric hypoxia (equivalent to a simulated altitude of 4200 m). Myocardial perfusion was assessed at baseline and after treatment with hypoxia by use of exercise perfusion imaging with technetium 99m sestamibi. After the sessions of hypoxia, myocardial perfusion was significantly improved. The summed stress score for hypoperfusion, in arbitrary units, decreased from 9.5+ to 4.5+ after treatment (P=.036). There was no evidence of impairment of myocardial perfusion in any patient after treatment. CONCLUSIONS: Intermittent hypobaric hypoxia improved myocardial perfusion in patients with severe coronary heart disease. Though preliminary, our results suggest that exposure to intermittent hypobaric hypoxia could be an alternative for the management of patients with chronic coronary heart disease.     

核医学放射性废水槽式衰变池容积的评价与设计

目的:提供评价与设计核医学槽式衰变池容积的计算方法,为医疗机构、环境影响评价机构和管理部门等提供技术参考。方法:通过构建数学模型并推导计算式,建立槽式衰变池容积与废水放射性水平之间的关系。结果:不同医疗机构的核医学科患者诊疗量、核素使用量以及废水产生量等存在差异,槽式衰变池的评价与设计的结果也不相同,但结果均应符合GB...     

The mathematical model of the blood circulation and external respiration functional state during high-pressure oxygenation or hyperoxia]

Based on the minimal energy uptake, the proposed mathematical model of blood circulation and external respiration functioning during high-pressure oxygenation or hyperoxia allows solution of the optimization task with restrictions dictated by adequate functioning of the two systems. Optimal levels of oxygen and carbon dioxide pressure in arterial and venous blood, minute blood volume and alveolar ventilation as a function of O2 partial pressure in inspired gas mixture were determined. Calculations are compared with experimentally derived values.     

慢性间歇性低压低氧改善全脑照射造成的小鼠记忆认知功能障碍的研究

目的 观察全脑照射后小鼠海马(CA)1区损伤的表现,探讨慢性间歇性低压低氧(CIHH)预处理对全脑照射后小鼠记忆认知功能的影响。方法 采用完全随机法将48只成年雄性C57BL/6小鼠分为健康对照组、CIHH组、单纯照射组(IR)和CIHH+IR组。IR组采用6MV X射线单次10 Gy全脑照射构建脑损伤模型。CIHH处理为小鼠在接受照射前置于低压氧舱预处理。Mirrors水迷宫实验观察小鼠逃避潜伏期、穿越平台次数以及目标象限停留时间,应用尼氏染色法观察海马CA1区神经元细胞的变化,应用免疫荧光法检测小鼠神经元前体细胞的微管相关蛋白(DCX)在海马齿状回(DG)颗粒下区(SGZ)的表达来评价神经发生情况。结果 全脑照射后30 d,IR组与健康对照组相比,小鼠逃避潜伏期延长,穿越平台次数减少(P＜0.001),目标象限内探索时间减少(P＜0.001)。X射线引起小鼠CA1区神经元细胞排列紊乱、神经元细胞变性、坏死,小鼠CA1区DCX表达量明显减少。与IR组比较,CIHH+IR组可使小鼠逃避潜伏期缩短,穿越平台次数增加[(2.08±0.26)次vs. (0.83±0.24)次,P＜0.001],目标象限内探索时间增加[(14.12±0.82)s vs. (7.42±0.73)s],P＜0.001］。小鼠CA1区神经元变形、坏死减少,排列紊乱改善,CA1区DCX表达量增加。结论 CIHH预处理对放射性海马损伤起到一定保护作用。     

EPO, red cells, and serum transferrin receptor in continuous and intermittent hypoxia

PURPOSE: Erythropoietic response in 10 healthy nonsmoking volunteers exposed to normobaric hypoxia continuously or intermittently 12 h daily for 7 d was evaluated in a randomized cross-over study. METHODS: An oxygen content of 15.4% corresponding to an altitude of 2500 m was created by adding nitrogen into room air in a flat. Venous blood samples for hemoglobin (Hb), hematocrit (Hct), reticulocytes, serum erythropoietin (S-EPO), red cell 2,3-diphosphoglycerate (2,3-DPG), serum ferritin (S-Ferrit), and serum soluble transferrin receptor (S-TransfR) were drawn at 8:00 a.m. RESULTS: S-EPO was increased from baseline values of 22.9+/-9.6 and 20.5+/-10.1 U x L(-1) to 40.7+/-12.9 (P < 0.05) and 35+/-14.3 U x L(-1) (P < 0.05) after the first night in continuous and intermittent hypoxia, respectively, and remained elevated throughout both exposures. Hb and Hct values did not show any significant changes. Red cell 2,3-DPG rose from baseline a value of 5.0+/-0.8 to 5.9+/-0.7 mmol x L(-1) (P < 0.05) after the first day in continuous hypoxia and from 5.2+/-0.7 mmol x L(-1) to 6.1+/-0.5 mmol x L(-1) on day 3 (P < 0.05) during intermittent hypoxia. The reticulocyte count rose significantly (P < 0.05) after 5 d in both experiments. S-transferrin receptor level rose significantly from 2.2+/-0.4 and 2.1+/-0.5 mg x L(-1) to 2.6+/-0.5 mg x L(-1) and 2.3+/-0.6 mg x L(-1) on day 5 (P < 0.05), to 2.7+/-0.5 mg x L(-1) and 2.5+/-0.6 mg x L(-1) on day 7 (P < 0.05) under continuous and intermittent hypoxia, respectively. CONCLUSIONS: We suggest that intermittent exposure to moderate normobaric hypoxia 12 h daily for 1 wk induces a similar stimulation of erythropoiesis as continuous exposure.