Low intense physical exercise in normobaric hypoxia leads to more weight loss in obese people than low intense physical exercise in normobaric sham hypoxia

Training in mild to moderate hypoxia (14–17% O2 in breathing air) and extended resting in moderate hypoxia (9–13% O2) have been shown to have effects in animals and humans on lipid and glucose metabolism, appetite loss, and, in part, on body weight. The causality for these effects is not yet known in detail, and the available data in humans from high-altitude and low-pressure chamber studies are scarce. New technical developments by German companies in the production of artificial climates with normobaric hypoxic conditions in larger rooms at reasonable energy costs allow now to perform hypoxia weight loss studies in obese humans with stable experimental conditions and protocols with a sham hypoxia control. Thirty-two obese people were recruited for a mild intense training study in normobaric hypoxia (15 vol.% O2) and normoxia/sham hypoxia (20.1 vol.% O2). Twenty of these [mean age 47.6 years, mean body mass index (BMI) 33.1, 16 m, 4 f) were willing to follow up on an 8-week, three times per week, 90-min low intense physical exercise in their individual fat burning mode, which has been determined by an exercise testing with spiro-ergometry upfront. The subjects were evenly randomized into a hypoxia and sham hypoxia group. The difference of the two groups in weight loss and changes in HBa1C values were analyzed before and after the training period. No nutritional diet was applied. Subjects in the hypoxia group in mean lost significantly more weight than in the sham hypoxia group (Δ1.14 kg vs Δ0.03 kg; p = 0.026). This resulted in a tendency to reduce the BMI more in the hypoxia group (p = 0.326). In the mean, there was no HbA1C exceeding normal values (mean 5.67 and 5.47%), and the HbA1C stayed basically unchanged after the 8-week training. Mild physical exercise three times per week for 90 min in normobaric hypoxia for 8 weeks led to significantly greater weight loss in obese persons than the exercise in sham hypoxia in this, to our knowledge, first sham hypoxia controlled study

Phosphodiesterase-5 Inhibition Mimics Intermittent Reoxygenation and Improves Cardioprotection in the Hypoxic Myocardium

Although chronic hypoxia is a claimed myocardial risk factor reducing tolerance to ischemia/reperfusion (I/R), intermittent reoxygenation has beneficial effects and enhances heart tolerance to I/R. Aim of the study: To test the hypothesis that, by mimicking intermittent reoxygenation, selective inhibition of phosphodiesterase-5 activity improves ischemia tolerance during hypoxia. Adult male Sprague-Dawley rats were exposed to hypoxia for 15 days (10% O2) and treated with placebo, sildenafil (1.4 mg/kg/day, i. p.), intermittent reoxygenation (1 h/day exposure to room air) or both. Controls were normoxic hearts. To assess tolerance to I/R all hearts were subjected to 30-min regional ischemia by left anterior descending coronary artery ligation followed by 3 h-reperfusion. Whereas hypoxia depressed tolerance to I/R, both sildenafil and intermittent reoxygenation reduced the infarct size without exhibiting cumulative effects. The changes in myocardial cGMP, apoptosis (DNA fragmentation), caspase-3 activity (alternative marker for cardiomyocyte apoptosis), eNOS phosphorylation and Akt activity paralleled the changes in cardioprotection. However, the level of plasma nitrates and nitrites was higher in the sildenafil+intermittent reoxygenation than sildenafil and intermittent reoxygenation groups, whereas total eNOS and Akt proteins were unchanged throughout. Conclusions: Sildenafil administration has the potential to mimic the cardioprotective effects led by intermittent reoxygenation, thereby opening the possibility to treat patients unable to be reoxygenated through a pharmacological modulation of NO-dependent mechanisms

Transcriptome and Network Changes in Climbers at Extreme Altitudes

Extreme altitude can induce a range of cellular and systemic responses. Although it is known that hypoxia underlies the major changes and that the physiological responses include hemodynamic changes and erythropoiesis, the molecular mechanisms and signaling pathways mediating such changes are largely unknown. To obtain a more complete picture of the transcriptional regulatory landscape and networks involved in extreme altitude response, we followed four climbers on an expedition up Mount Xixiabangma (8,012 m), and collected blood samples at four stages during the climb for mRNA and miRNA expression assays. By analyzing dynamic changes of gene networks in response to extreme altitudes, we uncovered a highly modular network with 7 modules of various functions that changed in response to extreme altitudes. The erythrocyte differentiation module is the most prominently up-regulated, reflecting increased erythrocyte differentiation from hematopoietic stem cells, probably at the expense of differentiation into other cell lineages. These changes are accompanied by coordinated down-regulation of general translation. Network topology and flow analyses also uncovered regulators known to modulate hypoxia responses and erythrocyte development, as well as unknown regulators, such as the OCT4 gene, an important regulator in stem cells and assumed to only function in stem cells. We predicted computationally and validated experimentally that increased OCT4 expression at extreme altitude can directly elevate the expression of hemoglobin genes. Our approach established a new framework for analyzing the transcriptional regulatory network from a very limited number of samples

Markers of physiological stress during exercise under conditions of normoxia, normobaric hypoxia, hypobaric hypoxia and genuine high altitude.

Purpose To investigate whether there is a differential response at rest and following exercise to conditions of genuine high altitude (GHA), normobaric hypoxia (NH), hypobaric hypoxia (HH) and normobaric normoxia (NN). Method Markers of sympathoadrenal and adrenocortical function (plasma normetanephrine [PNORMET], metanephrine [PMET], cortisol), myocardial injury (highly sensitive cardiac troponin T [hscTnT]) and function (N-terminal brain natriuretic peptide [NT-proBNP]) were evaluated at rest and with exercise under NN, at 3375 m in the Alps (GHA) and at equivalent simulated altitude under NH and HH. Participants cycled for 2 hours {15 minute warm-up, 105 minutes at 55% Wmax (maximal workload)} with venous blood samples taken prior (T0), immediately following (T120) and 2 hours post-exercise (T240). Results Exercise in the three hypoxic environments produced a similar pattern of response with the only difference between environments being in relation to PNORMET. Exercise in NN only induced a rise in PNORMET and PMET. Conclusion Biochemical markers that reflect sympathoadrenal, adrenocortical and myocardial responses to physiological stress demonstrate significant differences in the response to exercise under conditions of normoxia versus hypoxia while NH and HH appear to induce broadly similar responses to GHA and may therefore be reasonable surrogates

Peripheral chemoreflex function in hyperoxia following ventilatory acclimatization to altitude.

After a period of ventilatory acclimatization to high altitude (VAH), a degree of hyperventilation persists after relief of the hypoxic stimulus. This is likely, in part, to reflect the altered acid-base status, but it may also arise, in part, from the development during VAH of a component of carotid body (CB) activity that cannot be entirely suppressed by hyperoxia. To test this hypothesis, eight volunteers undergoing a simulated ascent of Mount Everest in a hypobaric chamber were acutely exposed to 30 min of hyperoxia at various stages of acclimatization. For the second 10 min of this exposure, the subjects were given an infusion of the CB inhibitor, dopamine (3 microg. kg(-1). min(-1)). Although there was both a significant rise in ventilation (P < 0.001) and a fall in end-tidal PCO(2) (P < 0.001) with VAH, there was no progressive effect of dopamine infusion on these variables with VAH. These results do not support a role for CB in generating the persistent hyperventilation that remains in hyperoxia after VAH