For the first time, we conducted a population-based study to evaluate the effect of hypoxic preacclimatization combining IHE and physical exercise in a hypobaric chamber among the lowlanders. IHE induces increase of blood oxygen saturation mainly due to efficient ventilatory acclimatization [20, 21]. SpO2 level is not only reflection of pulmonary oxygenation function and oxygen carrying capacity of hemoglobin under hypoxic environment, but also usually used as a noninvasive parameter for monitoring exercise intensity in hypoxic trainings [22]. A 7-week IHE under hypobaric pressure with mean total exposure time of 30.8 hours has been reported to increase SaO2 by 4.1% at 4570m [23]. Similarly, we observed an average increase of more than 5 percentage points of SpO2 among the groups with 5-day rest and 5-day physical exercise as compared with the control group. Hypoxic preacclimatization has probably resulted in an acclimation response with shorter time than predicted. Nevertheless, it should be noted that although SpO2 is significantly correlated with SaO2 in most cases, it may not be reliable surrogate marker for SaO2 in critically ill patients as well as in hypoxemia for increased bias and decreased accuracy and precision [24, 25]. HRs of the subjects with 5-day rest were significantly lowered as compared with the controls, however, no matter 5 days or 3 days of physical exercise seemed to have no obvious effect on HR. When exercising at certain intensity, the changes of HR among the subjects with IHE training are smaller than those without hypoxic training, indicating that IHE can compensate for the decrease of HR by increasing cardiac output and improve the cardiovascular function [26]. These results indicated that hypoxic preacclimatization with longer hypoxia time rather than more intensive physical exercise were more conducive to increase blood oxygen saturation and reduce heart rate.
The altitude and speed of ascent are considered to be the most important risk factors for AMS [27]. Although IHE is the best established intervention to improve high altitude hypoxia tolerance and most observations have indeed confirmed its positive effect on the prevention of AMS, the conclusions are still inconsistent. Within the first 6h of evaluation stage, those with hypoxic preacclimatization of 3-day exercise in the hypobaric chamber had the lowest AMS incidence of 33.33%, while the difference was still not significant. Another hypoxic preacclimatization training for 1h a day for 7 consecutive days also has no effect on preventing AMS when entering an altitude of 4500m [28]. The hypoxic preacclimatization in this study seemed to be ineffective in preventing AMS. The physiological changes of cardiovascular, respiratory, and nervous systems induced in 3 or 5 days’ hypoxic preacclimatization may be not insufficient to compensatory for the drastic decrease in ambient oxygen partial pressure.
IHE not only relieves the neurological symptoms of AMS, but also improves the cognitive level and mood at high altitudes [29, 30]. Exercise can also improve cognitive performance under both hypoxia and normoxia, although the beneficial effect under severe hypoxia may be attenuated [31–33]. The cognitive performance during exercising under acute hypoxia is primarily determined by alterations in cerebral blood flow, cerebral metabolism, and possibly neurotransmitter function [34]. In this study, 5-day IHE with physical exercise showed significant effect on perceptual speed, motor skills, and color selective reaction times. Hypoxia exposure of longer duration probably interacted positively with physical exercise of moderate intensity in improving hypoxic tolerance of the brain tissue. During this process, a variety of kinase cascades in brain cells may be initiated and induce changes in chromatin structure through epigenetic mechanisms [35]. The possible mechanisms also include activation of transcription factors, such as HIF and changes in expression of a variety of regulatory proteins.
IHE improves VO2max as well as lactate tolerance, and therefore effectively improves the aerobic exercise ability of athletes [36]. A 9-day hypobaric hypoxia exposure at simulated altitude from 4000 m to 5500 m has significantly activated the erythropoietic response and improved the aerobic capacity [37]. Hypoxic preacclimatization of 5-day exercise in this study has also significantly increased the VO2max. Generally, longer hypoxic preacclimatization combining moderate intensity of physical exercise is more effective in improving both mental and physical ability under hypoxia environment.
We found that daily hypoxia exposure of ≥ 3 days, lasting for ≥ 3h for each one along with the total training time of ≥ 10h at simulated altitude of ≥ 4000m may be efficient in inducing hypoxic acclimatization, which also seemed to be a protocol with shorter time as compared with those recommend by others [38, 39]. It has been implicated that the acclimatization effect of hypoxic preacclimatization protocols with short duration was not different between rest and exercise while protocols with exercise and longer duration could greatly enhance the exercise performance at high altitude [40]. Similarly, among the three protocols in this study, IHE combining 5-day exercise in the hypobaric chamber was the most effective one in promoting hypoxic acclimatization, especially for improvement of mental and physical ability.
Limitations
This study also has several limitations. First, we failed to collect the intact data on the related physiological indexes, mental and physical ability before the training, we could not accurately evaluate the comparability between the control and experimental groups although they were matched in some key characteristics, such as age, sex, and history of high altitude exposure. Second, the sample size of each group was not large enough to draw conclusions with strong statistical power. Third, we did not conduct field effect evaluation at high altitude. Lastly, we failed to investigate the duration of effect maintenance, which is actually a very important aspect of hypoxic preacclimatization.