Simulated altitude is medicine: intermittent exposure to hypobaric hypoxia and cold accelerates injured skeletal muscle recovery.

Muscle injuries are the leading cause of sports casualties. Because of its high plasticity, skeletal muscle can respond to different stimuli to maintain and improve functionality. Intermittent hypobaric hypoxia (IHH) improves muscle oxygen delivery and utilization. Hypobaria coexists with cold in the biosphere, opening the possibility to consider the combined use of both environmental factors to achieve beneficial physiological adjustments. We studied the effects of IHH and cold exposure, separately and simultaneously, on muscle regeneration. Adult male rats were surgically injured in one gastrocnemius and randomly assigned to the following groups: (1) CTRL: passive recovery; (2) COLD: intermittently exposed to cold (4°C); (3) HYPO: submitted to IHH (4500 m); (4) COHY: exposed to intermittent simultaneous cold and hypoxia. Animals were subjected to these interventions for 4 h/day for 9 or 21 days. COLD and COHY rats showed faster muscle regeneration than CTRL, evidenced after 9 days at histological (dMHC-positive and centrally nucleated fibre reduction) and functional levels after 21 days. HYPO rats showed a full recovery from injury (at histological and functional levels) after 9 days, while COLD and COHY needed more time to induce a total functional recovery. IHH can be postulated as an anti-fibrotic treatment since it reduces collagen I deposition. The increase in the pSer473Akt/total Akt ratio observed after 9 days in COLD, HYPO and COHY, together with the increase in the pThr172AMPKα/total AMPKα ratio observed in the gastrocnemius of HYPO, provides clues to the molecular mechanisms involved in the improved muscle regeneration. KEY POINTS: Only intermittent hypobaric exposure accelerated muscle recovery as early as 9 days following injury at histological and functional levels. Injured muscles from animals treated with intermittent (4 h/day) cold, hypobaric hypoxia or a simultaneous combination of both stimuli regenerated histological structure and recovered muscle function 21 days after injury. The combination of cold and hypoxia showed a blunting effect as compared to hypoxia alone in the time course of the muscle recovery. The increased expression of the phosphorylated forms of Akt observed in all experimental groups could participate in the molecular cascade of events leading to a faster regeneration. The elevated levels of phosphorylated AMPKα in the HYPO group could play a key role in the modulation of the inflammatory response during the first steps of the muscle regeneration process.

Bioactivity of Macronutrients from Chlorella in Physical Exercise.

Chlorella is a marine microalga rich in proteins and containing all the essential amino acids. Chlorella also contains fiber and other polysaccharides, as well as polyunsaturated fatty acids such as linoleic acid and alpha-linolenic acid. The proportion of the different macronutrients in Chlorella can be modulated by altering the conditions in which it is cultured. The bioactivities of these macronutrients make Chlorella a good candidate food to include in regular diets or as the basis of dietary supplements in exercise-related nutrition both for recreational exercisers and professional athletes. This paper reviews current knowledge of the effects of the macronutrients in Chlorella on physical exercise, specifically their impact on performance and recovery. In general, consuming Chlorella improves both anaerobic and aerobic exercise performance as well as physical stamina and reduces fatigue. These effects seem to be related to the antioxidant, anti-inflammatory, and metabolic activity of all its macronutrients, while each component of Chlorella contributes its bioactivity via a specific action. Chlorella is an excellent dietary source of high-quality protein in the context of physical exercise, as dietary proteins increase satiety, activation of the anabolic mTOR (mammalian Target of Rapamycin) pathway in skeletal muscle, and the thermic effects of meals. Chlorella proteins also increase intramuscular free amino acid levels and enhance the ability of the muscles to utilize them during exercise. Fiber from Chlorella increases the diversity of the gut microbiota, which helps control body weight and maintain intestinal barrier integrity, and the production of short-chain fatty acids (SCFAs), which improve physical performance. Polyunsaturated fatty acids (PUFAs) from Chlorella contribute to endothelial protection and modulate the fluidity and rigidity of cell membranes, which may improve performance. Ultimately, in contrast to several other nutritional sources, the use of Chlorella to provide high-quality protein, dietary fiber, and bioactive fatty acids may also significantly contribute to a sustainable world through the fixation of carbon dioxide and a reduction of the amount of land used to produce animal feed.

Histomorphological and functional contralateral symmetry in the gastrocnemius muscles of the laboratory rat.

It is usual in anatomical and physiological research to assess the effects of some intervention on extremities (e.g., training programmes or injury recovery protocols) using one muscle for the intervention and its contralateral as control. However, the existence of laterality (left-handedness or right-handedness) in athletes of different specialities is widely recognized. In rats, gastrocnemius is one of the muscles most widely used because of its importance in locomotion and high relative limb mass. Since we have not found studies reporting laterality assessment on the morphology and function in rat gastrocnemius, our study aimed to evaluate the fibre histochemical, morphometrical and muscle force contractile properties between right and left gastrocnemius of the laboratory rat. Fibre-type proportion, fibre morphometrical measurements, muscle capillarization and muscle force properties were analysed in the right and left gastrocnemius of six male rats. No statistically significant differences (p = 0.265) were found in gastrocnemius to body weight ratio (‰) between right (6.55 ± 0.40) and left (6.49 ± 0.40) muscles. The muscles analysed showed a great degree of heterogeneity in fibre type distribution, having three clearly distinguished regions named red, mixed and white. In the three regions, there were no statistical differences in fibre type proportions between right and left gastrocnemius, as is indicated by the p-values (from 0.203 to 0.941) obtained after running t-Student paired tests for each fibre type. When analysing fibre cross-sectional area, individual fibre capillarization and fibre circularity, no significant differences between right and left gastrocnemius in any of these morphometrical parameters were found in any muscle region or fibre type. Most of the p-values (70%) resulting from running t-Student paired tests were higher than 0.400, and the lowest p-value was 0.115. Seemingly, global capillary and fibre densities were not statistically different between right and left sides in all muscle regions with p-values ranging from 0.337 to 0.812. Force parameters normalized to gastrocnemius mass (mN g-1 ) did not show any significant difference between right (PF = 74.0 ± 13.4, TF = 219.4 ± 13.0) and left (PF = 70.9 ± 10.7, TF = 213.0 ± 18.0) muscles with p = 0.623 (PF) and p = 0.514 (TF). Twitch time parameters (ms) also lacked significant differences between the two sides (CT: 43.4 ± 8.6 vs. 45.0 ± 14.3, p = 0.639; HRT: 77.6 ± 15.0 vs. 82.3 ± 25.3, p = 0.475). Finally, both muscles also showed similar (p = 0.718) fatigue properties. We did find an absence of laterality at the morphological and functional levels, which raises the possibility of using right and left gastrocnemius muscles interchangeably for experimental designs where one muscle is used to analyse data after a physiological intervention and its contralateral muscle plays the control role, thus allowing unbiased paired comparisons to derive accurate conclusions.

Benefits on Hematological and Biochemical Parameters of a High-Intensity Interval Training Program for a Half-Marathon in Recreational Middle-Aged Women Runners.

(1) Background: half-marathon races are popular among recreational runners, with increases in participation among middle-aged and women. We aimed to determine the effects of two half-marathon training programs on hematological and biochemical markers in middle-aged female recreational runners; (2) Methods: ten women (40 ± 7 years) followed moderate intensity continuous training (MICT), based on running volume below 80% V˙O2max, and another ten women followed high intensity interval training (HIIT) at 80%-100% V˙O2max, with less volume, and combined with eccentric loading exercise. Hematology, plasma osmolality, and plasma markers of metabolic status, muscle damage, inflammatory, and oxidative stress were measured before (S1) and after (S2) training and 24 h after the half-marathon (S3); (3) Results: both training programs had similar moderate effects at S2. However, the acute response at S3 induced different alterations. There was a greater decrease in cholesterol and triglyceride levels in MICT and reductions in markers of damage and inflammation in HIIT. Greater variability in some plasma markers at S3 in MICT suggests that there is inter-individual variability in the response to training; (4) Conclusions: HIIT led to better adaptation to the competition maybe because of the repeated exposure to higher oxygen consumption and eccentric loading exercise.

Physiological Effects of Intermittent Passive Exposure to Hypobaric Hypoxia and Cold in Rats.

The benefits of intermittent hypobaric hypoxia (IHH) exposure for health and its potential use as a training tool are well-documented. However, since hypobaric hypoxia and cold are environmental factors always strongly associated in the biosphere, additive or synergistic adaptations could have evolved in animals' genomes. For that reason, the aim of the present study was to investigate body composition and hematological and muscle morphofunctional responses to simultaneous intermittent exposure to hypoxia and cold. Adult male rats were randomly divided into four groups: (1) control, maintained in normoxia at 25°C (CTRL); (2) IHH exposed 4 h/day at 4,500 m (HYPO); (3) intermittent cold exposed 4 h/day at 4°C (COLD); and (4) simultaneously cold and hypoxia exposed (COHY). At the end of 9 and 21 days of exposure, blood was withdrawn and gastrocnemius (GAS) and tibialis anterior muscles, perigonadal and brown adipose tissue, diaphragm, and heart were excised. GAS transversal sections were stained for myofibrillar ATPase and succinate dehydrogenase for fiber typing and for endothelial ATPase to assess capillarization. Hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and glucose transporter 1 (GLUT1) from GAS samples were semi-quantified by Western blotting. COLD and HYPO underwent physiological adjustments such as higher brown adipose tissue weight and increase in blood-related oxygen transport parameters, while avoiding some negative effects of chronic exposure to cold and hypoxia, such as body weight and muscle mass loss. COHY presented an additive erythropoietic response and was prevented from right ventricle hypertrophy. Intermittent cold exposure induced muscle angiogenesis, and IHH seems to indicate better muscle oxygenation through fiber area reduction.

Edible Microalgae and Their Bioactive Compounds in the Prevention and Treatment of Metabolic Alterations.

Marine and freshwater algae and their products are in growing demand worldwide because of their nutritional and functional properties. Microalgae (unicellular algae) will constitute one of the major foods of the future for nutritional and environmental reasons. They are sources of high-quality protein and bioactive molecules with potential application in the modern epidemics of obesity and diabetes. They may also contribute decisively to sustainability through carbon dioxide fixation and minimization of agricultural land use. This paper reviews current knowledge of the effects of consuming edible microalgae on the metabolic alterations known as metabolic syndrome (MS). These microalgae include Chlorella, Spirulina (Arthrospira) and Tetraselmis as well as Isochrysis and Nannochloropsis as candidates for human consumption. Chlorella biomass has shown antioxidant, antidiabetic, immunomodulatory, antihypertensive, and antihyperlipidemic effects in humans and other mammals. The components of microalgae reviewed suggest that they may be effective against MS at two levels: in the early stages, to work against the development of insulin resistance (IR), and later, when pancreatic -cell function is already compromised. The active components at both stages are antioxidant scavengers and anti-inflammatory lipid mediators such as carotenoids and -3 PUFAs (eicosapentaenoic acid/docosahexaenoic acid; EPA/DHA), prebiotic polysaccharides, phenolics, antihypertensive peptides, several pigments such as phycobilins and phycocyanin, and some vitamins, such as folate. As a source of high-quality protein, including an array of bioactive molecules with potential activity against the modern epidemics of obesity and diabetes, microalgae are proposed as excellent foods for the future. Moreover, their incorporation into the human diet would decisively contribute to a more sustainable world because of their roles in carbon dioxide fixation and reducing the use of land for agricultural purposes.

Inter-Individual Different Responses to Continuous and Interval Training in Recreational Middle-Aged Women Runners.

A crucial subject in sports is identifying the inter-individual variation in response to training, which would allow creating individualized pre-training schedules, improving runner's performance. We aimed to analyze heterogeneity in individual responses to two half-marathon training programs differing in running volume and intensity in middle-aged recreational women. 20 women (40 ± 7 years, 61 ± 7 kg, 167 ± 6 cm, and VO2max = 48 ± 6 mL⋅kg-1⋅min-1) underwent either moderate-intensity continuous (MICT) or high-intensity interval (HIIT) 12-week training. They were evaluated before and after training with maximal incremental tests in the laboratory (VO2max) and in the field (time to exhaustion, TTE; short interval series and long run). All the women participated in the same half-marathon and their finishing times were compared with their previous times. Although the improvements in the mean finishing times were not significant, MICT elicited a greater reduction (3 min 50 s, P = 0.298), with more women (70%) improving on their previous times, than HIIT (reduction of 2 min 34 s, P = 0.197, 50% responders). Laboratory tests showed more differences in the HIIT group (P = 0.008), while both groups presented homogeneous significant (P < 0.05) increases in TTE. Both in the short interval series and in the long run, HIIT induced better individual improvements, with a greater percentage of responders compared to MICT (100% vs 50% in the short series and 78% vs 38% in the long run). In conclusion, variability in inter-individual responses was observed after both MICT and HIIT, with some participants showing improvements (responders) while others did not (non-responders) in different performance parameters, reinforcing the idea that individualized training prescription is needed to optimize performance.

Implication of gut microbiota in the physiology of rats intermittently exposed to cold and hypobaric hypoxia.

This study examines the influence of intermittent exposure to cold, hypobaric hypoxia, and their combination, in gut microbiota and their metabolites in vivo, and explores their effects on the physiology of the host. Sprague-Dawley rats were exposed to cold (4°C), hypobaric hypoxia (462 torr), or both simultaneously, 4 h/day for 21 days. Biometrical and hematological parameters were monitored. Gut bacterial subgroups were evaluated by qPCR and short-chain fatty acids were determined by gas chromatography in caecum and feces. Cold increased brown adipose tissue, Clostridiales subpopulation and the concentration of butyric and isovaleric acids in caecum. Hypobaric hypoxia increased hemoglobin, red and white cell counts and Enterobacteriales, and reduced body and adipose tissues weights and Lactobacilliales. Cold plus hypobaric hypoxia counteracted the hypoxia-induced weight loss as well as the increase in white blood cells, while reducing the Bacteroidetes:Firmicutes ratio and normalizing the populations of Enterobacteriales and Lactobacilliales. In conclusion, intermittent cold and hypobaric hypoxia exposures by themselves modified some of the main physiological variables in vivo, while their combination kept the rats nearer to their basal status. The reduction of the Bacteroidetes:Firmicutes ratio and balanced populations of Enterobacteriales and Lactobacilliales in the gut may contribute to this effect.

Un ejemplo de respuesta adaptativa integrada: la aclimatación humana a la altitud / An example of integrated adaptive response: human acclimatization to altitude

Se describen las respuestas fisiológicas que el ser humano desarrolla en respuesta a la exposición a la altitud geográfica. Se describen no sólo las alteraciones debidas a una mala coordinación de los ajustes fisiológicos desencadenados durante la aclimatación a la altura sino también sus manifestaciones clínicas más relevantes. Se detallan los mecanismos moleculares subyacentes a tales respuestas y cómo su mejor conocimiento puede permitir aplicar la exposición intermitente a hipoxia como una herramienta útil para la resolución o alivio de determinadas alteraciones y patologías.

We depict the physiological responses developed by the human body in response to the exposure to geographic altitude. The main alterations due to a noncoordinated setup of the physiological adjustments triggered during the acclimatization at altitude are also described, as its most relevant clinical manifestations. The molecular mechanisms underlying such responses are detailed, and how a better knowledge of these processes can allow us to apply intermittent exposure to hypoxia programs as a useful tool for the resolution or relief of certain disorders and pathologies.

High-intensity interval versus moderate-intensity continuous half-marathon training programme for middle-aged women.

PURPOSE: To test the effectiveness on recreational female middle-aged runners of a programme of high-intensity interval training (HIIT) for a half-marathon race contrasted to a conventional moderate-intensity continuous training (MICT). METHODS: Twenty recreational female runners (40 ± 7 years) followed MICT or HIIT schedules for training a half-marathon. The MICT group trained a mean of 32 km/week at intensities below 80% VO2max. The HIIT group ran 25 km/week at intensities between 80 and 100% VO2max, combined with uphill running and resistance training. Women following HIIT ran 21% less distance and invested 17% less time than those from MICT group. All the women were evaluated at the beginning and end of the training and participated in the same half-marathon run. RESULTS: Women following both schedules reduced their previous finishing times by 2-3%, which for HIIT group would have meant rising up to 90 positions out of 1454 participants in the local half-marathon race. The high intensity performed during series of high power output (200 m and 400 m) and resistance sessions in HIIT programme promoted changes that allowed modifying efficiency at high workloads. At the same time, the HIIT training programme elicited changes in oxygen uptake and transport as indicated the cardiorespiratory parameters obtained during recovery in lab tests. Moreover, HIIT registered a 14% baseline decrease in heart rate contrasting to the not significant 6% decrease in MICT. CONCLUSIONS: Runners following HIIT training obtained similar registers as with a traditional MICT schedule, expending less time and running shorter distances, yet improving their anaerobic and aerobic power.

A three-criteria performance score for rats exercising on a running treadmill.

In this study, we propose a novel three-criteria performance score to semiquantitatively classify the running style, the degree of involvement and compliance and the validity of electric shock count for rats exercising on a treadmill. Each score criterion has several style-marks that are based on the observational registry of male Sprague-Dawley rats running for 4-7 weeks. Each mark was given a score value that was averaged throughout a session-registry and resulting in a session score for each criterion, ranging from "0" score for a hypothetical "worst runner", to score "1" for a hypothetical "perfect runner" rat. We found significant differences throughout a training program, thus providing evidence of sufficient sensitivity of this score to reflect the individual evolution of performance improvement in exercise capacity due to training. We hypothesize that this score could be correlated with other physiological or metabolic parameters, thus refining research results and further helping researchers to reduce the number of experimental subjects.

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

In recent years, the altitude acclimatization responses elicited by short-term intermittent exposure to hypoxia have been subject to renewed attention. The main goal of short-term intermittent hypobaric hypoxia exposure programs was originally to improve the aerobic capacity of athletes or to accelerate the altitude acclimatization response in alpinists, since such programs induce an increase in erythrocyte mass. Several model programs of intermittent exposure to hypoxia have presented efficiency with respect to this goal, without any of the inconveniences or negative consequences associated with permanent stays at moderate or high altitudes. Artificial intermittent exposure to normobaric hypoxia systems have seen a rapid rise in popularity among recreational and professional athletes, not only due to their unbeatable cost/efficiency ratio, but also because they help prevent common inconveniences associated with high-altitude stays such as social isolation, nutritional limitations, and other minor health and comfort-related annoyances. Today, intermittent exposure to hypobaric hypoxia is known to elicit other physiological response types in several organs and body systems. These responses range from alterations in the ventilatory pattern to modulation of the mitochondrial function. The central role played by hypoxia-inducible factor (HIF) in activating a signaling molecular cascade after hypoxia exposure is well known. Among these targets, several growth factors that upregulate the capillary bed by inducing angiogenesis and promoting oxidative metabolism merit special attention. Applying intermittent hypobaric hypoxia to promote the action of some molecules, such as angiogenic factors, could improve repair and recovery in many tissue types. This article uses a comprehensive approach to examine data obtained in recent years. We consider evidence collected from different tissues, including myocardial capillarization, skeletal muscle fiber types and fiber size changes induced by intermittent hypoxia exposure, and discuss the evidence that points to beneficial interventions in applied fields such as sport science. Short-term intermittent hypoxia may not only be useful for healthy people, but could also be considered a promising tool to be applied, with due caution, to some pathophysiological states.

Additive Effects of Intermittent Hypobaric Hypoxia and Endurance Training on Bodyweight, Food Intake, and Oxygen Consumption in Rats.

Cabrera-Aguilera, Ignacio, David Rizo-Roca, Elisa A. Marques, Garoa Santocildes, Teresa Pagès, Gines Viscor, António A. Ascensão, José Magalhães, and Joan Ramon Torrella. Additive effects of intermittent hypobaric hypoxia and endurance training on bodyweight, food intake, and oxygen consumption in rats. High Alt Med Biol. 19:278-285, 2018.-We used an animal model to elucidate the effects of an intermittent hypobaric hypoxia (IHH) and endurance exercise training (EET) protocol on bodyweight (BW), food and water intake, and oxygen consumption. Twenty-eight young adult male rats were divided into four groups: normoxic sedentary (NS), normoxic exercised (NE), hypoxic sedentary (HS), and hypoxic exercised (HE). Normoxic groups were maintained at an atmospheric pressure equivalent to sea level, whereas the IHH protocol consisted of 5 hours per day for 33 days at a simulated altitude of 6000 m. Exercised groups ran in normobaric conditions on a treadmill for 1 hour/day for 5 weeks at a speed of 25 m/min. At the end of the protocol, both hypoxic groups showed significant decreases in BW from the ninth day of exposure, reaching final 10% (HS) to 14.5% (HE) differences when compared with NS. NE rats also showed a significant weight reduction after the 19th day, with a decrease of 7.4%. The BW of hypoxic animals was related to significant hypophagia elicited by IHH exposure (from 8% to 12%). In contrast, EET had no effect on food ingestion. Total water intake was not affected by hypoxia but was significantly increased by exercise. An analysis of oxygen consumption at rest (mL O2/[kg·min]) revealed two findings: a significant decrease in both hypoxic groups after the protocol (HS, 21.7 ± 0.70 vs. 19.1 ± 0.78 and HE, 22.8 ± 0.80 vs. 17.1 ± 0.90) and a significant difference at the end of the protocol between NE (21.3 ± 0.77) and HE (17.1 ± 0.90). These results demonstrate that IHH and EET had an additive effect on BW loss, providing evidence that rats underwent a metabolic adaptation through a reduction in oxygen consumption measured under normoxic conditions. These data suggest that the combination of IHH and EET could serve as an alternative treatment for the management of overweight and obesity.

Contractile Activity Is Necessary to Trigger Intermittent Hypobaric Hypoxia-Induced Fiber Size and Vascular Adaptations in Skeletal Muscle.

Altitude training has become increasingly popular in recent decades. Its central and peripheral effects are well-described; however, few studies have analyzed the effects of intermittent hypobaric hypoxia (IHH) alone on skeletal muscle morphofunctionality. Here, we studied the effects of IHH on different myofiber morphofunctional parameters, investigating whether contractile activity is required to elicit hypoxia-induced adaptations in trained rats. Eighteen male Sprague-Dawley rats were trained 1 month and then divided into three groups: (1) rats in normobaria (trained normobaric inactive, TNI); (2) rats subjected daily to a 4-h exposure to hypobaric hypoxia equivalent to 4,000 m (trained hypobaric inactive, THI); and (3) rats subjected daily to a 4-h exposure to hypobaric hypoxia just before performing light exercise (trained hypobaric active, THA). After 2 weeks, the tibialis anterior muscle (TA) was excised. Muscle cross-sections were stained for: (1) succinate dehydrogenase to identify oxidative metabolism; (2) myosin-ATPase to identify slow- and fast-twitch fibers; and (3) endothelial-ATPase to stain capillaries. Fibers were classified as slow oxidative (SO), fast oxidative glycolytic (FOG), fast intermediate glycolytic (FIG) or fast glycolytic (FG) and the following parameters were measured: fiber cross-sectional area (FCSA), number of capillaries per fiber (NCF), NCF per 1,000 µm2 of FCSA (CCA), fiber and capillary density (FD and CD), and the ratio between CD and FD (C/F). THI rats did not exhibit significant changes in most of the parameters, while THA animals showed reduced fiber size. Compared to TNI rats, FOG fibers from the lateral/medial fields, as well as FIG and FG fibers from the lateral region, had smaller FCSA in THA rats. Moreover, THA rats had increased NCF in FG fibers from all fields, in medial and posterior FIG fibers and in posterior FOG fibers. All fiber types from the three analyzed regions (except the posterior FG fibers) displayed a significantly increased CCA ratio compared to TNI rats. Global capillarisation was also increased in lateral and medial fields. Our results show that IHH alone does not induce alterations in the TA muscle. The inclusion of exercise immediately after the tested hypoxic conditions is enough to trigger a morphofunctional response that improves muscle capillarisation.

Modulation of mitochondrial biomarkers by intermittent hypobaric hypoxia and aerobic exercise after eccentric exercise in trained rats.

Unaccustomed eccentric contractions induce muscle damage, calcium homeostasis disruption, and mitochondrial alterations. Since exercise and hypoxia are known to modulate mitochondrial function, we aimed to analyze the effects on eccentric exercise-induced muscle damage (EEIMD) in trained rats using 2 recovery protocols based on: (i) intermittent hypobaric hypoxia (IHH) and (ii) IHH followed by exercise. The expression of biomarkers related to mitochondrial biogenesis, dynamics, oxidative stress, and bioenergetics was evaluated. Soleus muscles were excised before (CTRL) and 1, 3, 7, and 14 days after an EEIMD protocol. The following treatments were applied 1 day after the EEIMD: passive normobaric recovery (PNR), 4 h daily exposure to passive IHH at 4000 m (PHR) or IHH exposure followed by aerobic exercise (AHR). Citrate synthase activity was reduced at 7 and 14 days after application of the EEIMD protocol. However, this reduction was attenuated in AHR rats at day 14. PGC-1α and Sirt3 and TOM20 levels had decreased after 1 and 3 days, but the AHR group exhibited increased expression of these proteins, as well as of Tfam, by the end of the protocol. Mfn2 greatly reduced during the first 72 h, but returned to basal levels passively. At day 14, AHR rats had higher levels of Mfn2, OPA1, and Drp1 than PNR animals. Both groups exposed to IHH showed a lower p66shc(ser36)/p66shc ratio than PNR animals, as well as higher complex IV subunit I and ANT levels. These results suggest that IHH positively modulates key mitochondrial aspects after EEIMD, especially when combined with aerobic exercise.

¿Afecta sidenafilo a la capacidad física en altitud? Evidencias científicas en la actualidad / Can sildenafil improve physical performance at altitude? Current scientific evidence

Sildenafilo ha demostrado eficacia reduciendo la hipertensión pulmonar provocada por la vasoconstricción pulmonar hipóxica. Su papel como posible factor para aumentar el rendimiento en el ejercicio en condiciones de hipoxia está por demostrar, pero el uso de sildenafilo ha aumentado entre los montañeros, no como un fármaco preventivo del edema pulmonar de gran altitud, sino en la creencia de que podría ayudar a mejorar el rendimiento físico a gran altura geográfica. Varios estudios han tratado de abordar este tema, con resultados contradictorios. Actualmente, a pesar de que no hay datos concluyentes, ni en altitud simulada ni real, y con la clara evidencia de que en normoxia el sildenafilo no mejora el rendimiento físico, se continúa utilizando esta sustancia (a veces en exceso) por personas que suben a altas cumbres. Tal potencial mejora de rendimiento dependería del grado de hipoxemia (altitud) y de la capacidad de respuesta individual a este medicamento. El presente artículo revisa el conocimiento actual sobre este tema

Sildenafil has proven to efficiently reduce the increase in pulmonary artery pressure provoked by hypoxic pulmonary vasoconstriction. However, its role as a possible factor in increasing exercise performance under hypoxic conditions remains to be demonstrated. The use of sildenafil has increased among mountaineers, not as a high altitude pulmonary edema preventive drug, but as a means that could help to improve performance. Several studies have attempted to address this issue, with conflicting results. Currently, despite the inconclusive data at simulated or real altitude, and with the clear evidence that, in normoxia, sildenafil does not improve performance, this drug is being used (and sometimes overused) by people who climb high peaks. However, such potential performance improvement would depend on the degree of hypoxemia (altitude) and the individual responsiveness to this drug. This paper reviews the current knowledge on this matter

The influence of dental occlusion on the body balance in unstable platform increases after high intensity exercise.

Existing evidence suggests that body balance ability is associated with dental occlusion. The purpose of this study was to determine whether: (i) there are differences in balance between opposed dental occlusion (intercuspal position, ICP; cotton rolls, CR) for two extreme levels of stability and (ii) the influence of dental occlusion on the balance control gets stronger under fatigue conditions. To this aim, various measures for assessing postural control in ten physically active subjects were obtained prior to and following a maximal lower limbs exercise consisting in six sets of fifteen seconds stretch-shortening cycle jumping. Balance control at stable and unstable condition was evaluated on an unstable platform Balance System SD for both dental occlusion conditions at random order. Metabolic and psychological measurements ensured the high intensity of the exercise. At unstable level, balance control was significantly improved in the CR condition, for both rest (p=0.03) and fatigue (p<0.001). Whereas at stable level, the influence of dental occlusion only reached significance in fatigue condition (p=0.04). It could be concluded that the sensory information linked to the dental occlusion for the balance control comes strongly into effect when more difficult conditions for the balance control are present (i.e., unstable conditions, fatigue).

Vybrant DyeCycle Violet Stain Discriminates Two Different Subsets of CD34+ Cells.

INTRODUCTION: Studies are needed to understand the role of CD34 expressing cells with regard to efficient engraftment, especially in the adjuvant treatment of cancer. MATERIALS AND METHODS: In this study we have used a modified method in our laboratory for routinely counting CD34+ cells. Unlysed whole blood samples were stained with the DNA-selective and cell membrane-permeant Vibrant DyeCycle Violet stain. RESULTS: CD34+ cells exhibit a consistent and differential Vybrant Dye Cycle Violet staining pattern. Based on their different DCV intensity, we classified these subpopulations as CD34+/DCV(high) and CD34+/DCV(low) cells. In general, DCV(high) cells are about 12-times brighter than DCV(low) cells. CONCLUSION: DCV staining may be used to discriminate subsets of CD34+ cells similarly to other methods which have previously defined different functional properties that can be related to the characterization, resolution, and purification of primitive hematopoietic stem cells in combination with specific useful markers for multicolor flow cytometric measurements.

Circadian and Sex Differences After Acute High-Altitude Exposure: Are Early Acclimation Responses Improved by Blue Light?

OBJECTIVE: The possible effects of blue light during acute hypoxia and the circadian rhythm on several physiological and cognitive parameters were studied. METHODS: Fifty-seven volunteers were randomly assigned to 2 groups: nocturnal (2200-0230 hours) or diurnal (0900-1330 hours) and exposed to acute hypoxia (4000 m simulated altitude) in a hypobaric chamber. The participants were illuminated by blue LEDs or common artificial light on 2 different days. During each session, arterial oxygen saturation (Spo2), blood pressure, heart rate variability, and cognitive parameters were measured at sea level, after reaching the simulated altitude of 4000 m, and after 3 hours at this altitude. RESULTS: The circadian rhythm caused significant differences in blood pressure and heart rate variability. A 4% to 9% decrease in waking nocturnal Spo2 under acute hypoxia was observed. Acute hypoxia also induced a significant reduction (4%-8%) in systolic pressure, slightly more marked (up to 13%) under blue lighting. Women had significantly increased systolic (4%) and diastolic (12%) pressures under acute hypoxia at night compared with daytime pressure; this was not observed in men. Some tendencies toward better cognitive performance (d2 attention test) were seen under blue illumination, although when considered together with physiological parameters and reaction time, there was no conclusive favorable effect of blue light on cognitive fatigue suppression after 3 hours of acute hypobaric hypoxia. CONCLUSIONS: It remains to be seen whether longer exposure to blue light under hypobaric hypoxic conditions would induce favorable effects against fatigue.

Dental Occlusion Influences the Standing Balance on an Unstable Platform.

Contradictory results are still reported on the influence of dental occlusion on the balance control. We attempted to determine whether there are differences in balance between opposed dental occlusion (Intercuspal position (ICP)/"Cotton rolls" mandibular position [CR]) for two extreme levels of stability (stable/ unstable). Twenty-five subjects were monitored under both dental occlusion and level of stability conditions using an unstable platform Balance System SD. The resulting stability index suggests that body balance is significantly better when dental occlusion is set in CR (p < .001) in unstable but not in stable conditions. Occlusal traits significantly influencing postural control were Angle Class (p < .001), crowding (p = .006), midline deviation (p < .001), crossbite (p < .001), anterior open bite (p = .05), and overjet (p = .01). It could be concluded that the sensory information linked to the dental occlusion for the balance control comes strongly into effect in unstable conditions.