Exercise In Acute Hypoxia Research Articles

Hemodynamics and cerebral oxygenation during acute exercise in moderate normobaric hypoxia and with concurrent cognitive task in young healthy males.

The present investigation aimed to study the cardiovascular responses and the cerebral oxygenation (Cox) during exercise in acute hypoxia and with contemporary mental stress. Fifteen physically active, healthy males (age 29.0±5.9 years) completed a cardiopulmonary test on a cycle ergometer to determine the workload at their gas exchange threshold (GET). On a separate day, participants performed two randomly assigned exercise tests pedaling for 6 min at a workload corresponding to 80% of the GET: (1) during normoxia (NORMO), and (2) during acute, normobaric hypoxia at 13.5% inspired oxygen (HYPO). During the last 3 min of the exercise, they also performed a mental task (MT). Hemodynamics were assessed with impedance cardiography, and peripheral arterial oxygen saturation and Cox were continuously measured by near-infrared spectroscopy. The main results were that both in NORMO and HYPO conditions, the MT caused a significant increase in the heart rate and ventricular filling rate. Moreover, MT significantly reduced (74.8±5.5vs. 62.0±5.2 A.U.) Cox, while the reaction time (RT) increased (813.3±110.2vs. 868.2±118.1ms) during the HYPO test without affecting the correctness of the answers. We conclude that in young, healthy males, adding an MT during mild intensity exercise in both normoxia and acute moderate (normobaric) hypoxia induces a similar hemodynamic response. However, MT and exercise in HYPO cause a decrease in Cox and an impairment in RT.

Right ventricular performance during acute hypoxic exercise.

Acute hypoxia increases pulmonary arterial (PA) pressures, though its effect on right ventricular (RV) function is controversial. The objective of this study was to characterize exertional RV performance during acute hypoxia. Ten healthy participants (34±10 years, 7males) completed three visits: visits 1 and 2 included non-invasive normoxic (fraction of inspired oxygen ( )=0.21) and isobaric hypoxic ( =0.12) cardiopulmonary exercise testing (CPET) to determine normoxic/hypoxic maximal oxygen uptake ( ). Visit 3 involved invasive haemodynamic assessments where participants were randomized 1:1 to either Swan-Ganz or conductance catheterization to quantify RV performance via pressure-volume analysis. Arterial oxygen saturation was determined by blood gas analysis from radial arterial catheterization. During visit 3, participants completed invasive submaximal CPET testing at 50% normoxic and again at 50% hypoxic ( =0.12). Median (interquartile range) values for non-invasive values during normoxic and hypoxic testing were 2.98 (2.43, 3.66) l/min and 1.84 (1.62, 2.25) l/min, respectively (P<0.0001). Mean PA pressure increased significantly when transitioning from rest to submaximal exercise during normoxic and hypoxic conditions (P=0.0014). Metrics of RV contractility including preload recruitable stroke work, dP/dtmax, and end-systolic pressure increased significantly during the transition from rest to exercise under normoxic and hypoxic conditions. Ventricular-arterial coupling was maintained during normoxic exercise at 50% . During submaximal exercise at 50% of hypoxic , ventricular-arterial coupling declined but remained within normal limits. In conclusion, resting and exertional RV functions are preserved in response to acute exposure to hypoxia at an =0.12 and the associated increase in PA pressures. KEY POINTS: The healthy right ventricle augments contractility, lusitropy and energetics during periods of increased metabolic demand (e.g. exercise) in acute hypoxic conditions. During submaximal exercise, ventricular-arterial coupling decreases but remains within normal limits, ensuring that cardiac output and systemic perfusion are maintained. These data describe right ventricular physiological responses during submaximal exercise under conditions of acute hypoxia, such as occurs during exposure to high altitude and/or acute hypoxic respiratory failure.

Cardio-Respiratory and Muscle Oxygenation Responses to Submaximal and Maximal Exercise in Normobaric Hypoxia: Comparison between Children and Adults.

As differential physiological responses to hypoxic exercise between adults and children remain poorly understood, we aimed to comprehensively characterise cardiorespiratory and muscle oxygenation responses to submaximal and maximal exercise in normobaric hypoxia between the two groups. Following familiarisation, fifteen children (Age = 9 ± 1 years) and fifteen adults (Age = 22 ± 2 years) completed two graded cycling exercise sessions to exhaustion in a randomized and single-blind manner in normoxia (NOR; FiO2 = 20.9) and normobaric hypoxia (HYP; FiO2 = 13.0) exercises conditions. Age-specific workload increments were 25 W·3 min-1 for children and 40 W·3 min-1 for adults. Gas exchange and vastus lateralis oxygenation parameters were measured continuously via metabolic cart and near-infrared spectroscopy, respectively. Hypoxia provoked significant decreases in maximal power output PMAX (children = 29%; adults 16% (F = 39.3; p < 0.01)) and power output at the gas exchange threshold (children = 10%; adults:18% (F = 8.08; p = 0.01)) in both groups. Comparable changes were noted in most respiratory and gas exchange parameters at similar power outputs between groups. Children, however, demonstrated, lower PETCO2 throughout the test at similar power outputs and during the maintenance of V˙CO2 at the maximal power output. These data indicate that, while most cardiorespiratory responses to acute hypoxic exercise are comparable between children and adults, there exist age-related differential responses in select respiratory and muscle oxygenation parameters.

Acute Exercise with Moderate Hypoxia Reduces Arterial Oxygen Saturation and Cerebral Oxygenation without Affecting Hemodynamics in Physically Active Males.

Hemodynamic changes during exercise in acute hypoxia (AH) have not been completely elucidated. The present study aimed to investigate hemodynamics during an acute bout of mild, dynamic exercise during moderate normobaric AH. Twenty-two physically active, healthy males (average age; range 23–40 years) completed a cardiopulmonary test on a cycle ergometer to determine their maximum workload (Wmax). On separate days, participants performed two randomly assigned exercise tests (three minutes pedaling at 30% of Wmax): (1) during normoxia (NORMO), and (2) during normobaric AH at 13.5% inspired oxygen (HYPO). Hemodynamics were assessed with impedance cardiography, and peripheral arterial oxygen saturation (SatO2) and cerebral oxygenation (Cox) were measured by near-infrared spectroscopy. Hemodynamic responses (heart rate, stroke volume, cardiac output, mean arterial blood pressure, ventricular emptying rate, and ventricular filling rate) were not any different between NORMO and HYPO. However, the HYPO test significantly reduced both SatO2 (96.6 ± 3.3 vs. 83.0 ± 4.5%) and Cox (71.0 ± 6.6 vs. 62.8 ± 7.4 A.U.) when compared to the NORMO test. We conclude that an acute bout of mild exercise during acute moderate normobaric hypoxia does not induce significant changes in hemodynamics, although it can cause significant reductions in SatO2 and Cox.

Exogenous ketosis increases blood and muscle oxygenation but not performance during exercise in hypoxia.

Available evidence indicates that elevated blood ketones are associated with improved hypoxic tolerance in rodents. From this perspective, we hypothesized that exogenous ketosis by oral intake of the ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KE) may induce beneficial physiological effects during prolonged exercise in acute hypoxia. As we recently demonstrated KE to deplete blood bicarbonate, which per se may alter the physiological response to hypoxia, we evaluated the effect of KE both in the presence and absence of bicarbonate intake (BIC). Fourteen highly trained male cyclists performed a simulated cycling race (RACE) consisting of 3-h intermittent cycling (IMT180') followed by a 15-min time-trial (TT15') and an all-out sprint at 175% of lactate threshold (SPRINT). During RACE, fraction of inspired oxygen ([Formula: see text]) was gradually decreased from 18.6% to 14.5%. Before and during RACE, participants received either 1) 75 g of ketone ester (KE), 2) 300 mg/kg body mass bicarbonate (BIC), 3) KE+BIC, or 4) a control drink in addition to 60 g of carbohydrates/h in a randomized, crossover design. KE counteracted the hypoxia-induced drop in blood ([Formula: see text]) and muscle oxygenation by ∼3%. In contrast, BIC decreased [Formula: see text] by ∼2% without impacting muscle oxygenation. Performance during TT15' and SPRINT were similar between all conditions. In conclusion, KE slightly elevated the degree of blood and muscle oxygenation during prolonged exercise in moderate hypoxia without impacting exercise performance. Our data warrant to further investigate the potential of exogenous ketosis to improve muscular and cerebral oxygenation status, and exercise tolerance in extreme hypoxia.

Select DNA Replication And Repair Genes Are Transcriptionally Modified By Acute Exercise In Hypoxia

DNA replication and repair in eukaryote cells are critical processes that ensures the correct transfer of DNA material through mitosis. Errors in the replication and repair of DNA during and following cell division may lead to genome instability. PURPOSE: To investigate the regulation of select gene transcripts aligned to DNA replication and repair following exercise in hypoxia. METHODS: Twenty-four (n = 24) apparently healthy male participants were recruited (age 28 ± 5 years; mass 74 ± 8 kg; stature 177 ± 6 cm; VO2max hypoxia 45 ± 2 ml·kg-1·min-1: normoxia 60 ± 9 ml·kg-1·min-1), and completed 1 hr of exercise at a workload corresponding to 75% of pre-determined VO2max in hypoxia (Fio2 = 0.16%), and repeated in normoxia (Fio2 = 0.21%). RNA was extracted from whole blood. Two-colour oligonucleotide microarrays [for DNA primase subunit 1 - PRIM1; Chromatin assembly factor 1 subunit B - CHAF1B; and Werner syndrome RecQ like helicase - WRN] were processed on an Agilent DNA microarray scanner, while mRNA analysis was conducted using GeneSpring software incorporating checks for data normalisation, quality control, filtering grouping (by experimental condition) and statistical analysis (paired t-test with Benjamini & Hochberg False Discovery Rate corrections for multiple comparisons). RESULTS: Exercise performed in hypoxia per se downregulated PRIM1 and CHAF1B (p = 0.03 and p = 0.01 respectively vs. pre-exercise), with no change observed in normoxia (p > 0.05). Compared with normoxia, CHAF1B and WRN were differentially downregulated following exercise in hypoxia (p = 0.05 and p = 0.05 respectively vs. pre-exercise). CONCLUSION: Acute exercise in moderate hypoxia interferes with gene transcription aligned to blood cell DNA replication and repair. Further work is necessary to ascertain the consequence of these select modifications on genome stability.

Modelling the relationships between arterial oxygen saturation, exercise intensity and the level of aerobic performance in acute hypoxia

The aim of this study was to establish a model to estimate the level of arterial oxygen saturation (SpO2) and help determine the appropriate hypoxic dose in humans exercising in acute hypoxia. SpO2 values were collected in seven untrained (UTS) and seven endurance-trained male subjects (ETS) who performed six cycle incremental and maximal tests at sea level and at simulated altitudes of 1000, 1500, 2500, 3500 and 4500m. Oxygen uptake was continuously measured and maximal oxygen uptake ([Formula: see text]) was determined in each subject and at each altitude. Intensity was expressed as percentage of [Formula: see text]. There were strong non-linear relationships between altitude and SpO2 at low, moderate and high intensity both in ETS and UTS (r = 0.97, p < 0.001). SpO2 was significantly correlated to exercise intensity at sea level and at all simulated altitudes in ETS but only from 2500m in UTS. There were inverse correlations between SpO2 and sea-level [Formula: see text] at all altitudes, which were stronger from 2500m and with the increase in exercise intensity. The three-variable model we established predicts (p < 0.001) the SpO2 level of individuals exercising in acute hypoxia based on their sea-level [Formula: see text], the intensity of exercise and the altitude level. The model demonstrates that the drop of SpO2 during exercise in acute hypoxia is larger with the increase in both sea-level [Formula: see text] and exercise intensity. The model also highlights that the pivotal altitude from which the fall in SpO2 is exacerbated is between 2000 and 2500m, depending on both sea-level [Formula: see text] and exercise intensity.

Regulation of satellite cells by exercise in hypoxic conditions: a narrative review.

To investigate in vivo the adaptations of satellite cell induced by exercise performed in acute or chronic hypoxic conditions and their contribution to muscle remodeling and hypertrophy. Search terms related to exercise, hypoxia and satellite cells were entered on Embase, PubMed and Scopus. Studies were selected for their relevance in terms of regulation of satellite cells by in vivo exercise and muscle contraction in hypoxic conditions. Satellite cell activation and proliferation seem to be enabled after acute hypoxic exercise via regulations induced by myogenic regulatory factors. Several studies reported also a role of the inflammatory pathway nuclear factor-kappa B and angiogenic factors such as vascular endothelial growth factor, both known to upregulate myogenesis. By stimulating angiogenesis, repeated exercise performed in acute hypoxia might contribute to satellite cell activation. Contrary to such exercise conditions, chronic exposure to hypoxia downregulates myogenesis despite the maintenance of physical activity. This impaired myogenesis might be induced by excessive oxidative stress and proteolysis. In vivo studies suggest that, in comparison to exercise or hypoxia alone, exercise performed in a hypoxic environment, may improve or impair muscle remodeling induced by contractile activity depending upon the duration of hypoxia. Satellite cells seem to be major actors in these dichotomous adaptations. Further research on the role of angiogenesis, types of contraction and autophagy is needed for a better understanding of their respective role in hypoxic exercise-induced modulations of satellite cell activity in human.

Effect of hypoxic exercise on glucose tolerance in healthy and prediabetic adults

This study aimed to investigate the mechanisms known to regulate glucose homeostasis in human skeletal muscle of healthy and prediabetic subjects exercising in normobaric hypoxia. Seventeen healthy (H; 28.8 ± 2.4 yr; maximal oxygen consumption (V̇O2max): 45.1 ± 1.8 mL·kg-1·min-1) and 15 prediabetic (P; 44.6 ± 3.9 yr; V̇O2max: 30.8 ± 2.5 mL·kg-1·min-1) men were randomly assigned to two groups performing an acute exercise bout (heart rate corresponding to 55% V̇O2max) either in normoxic (NE) or in hypoxic (HE; fraction of inspired oxygen [Formula: see text] 14.0%) conditions. An oral glucose tolerance test (OGTT) was performed in a basal state and after an acute exercise bout. Muscle biopsies from m. vastus lateralis were taken before and after exercise. Venous blood samples were taken at regular intervals before, during, and after exercise. The two groups exercising in hypoxia had a larger area under the curve of blood glucose levels during the OGTT after exercise compared with baseline (H: +11%; P: +4%). Compared with pre-exercise, an increase in p-TBC1D1 Ser237 and in p-AMPK Thr172 was observed postexercise in P NE (+95%; +55%, respectively) and H HE (+91%; +43%, respectively). An increase in p-ACC Ser212 was measured after exercise in all groups (H NE: +228%; P NE: +252%; H HE: +252%; P HE: +208%). Our results show that an acute bout of exercise in hypoxia reduces glucose tolerance in healthy and prediabetic subjects. At a molecular level, some adaptations regulating glucose transport in muscle were found in all groups without associations with glucose tolerance after exercise. The results suggest that hypoxia negatively affects glucose tolerance postexercise through unidentified mechanisms.NEW & NOTEWORTHY The molecular mechanisms involved in glucose tolerance after acute exercise in hypoxia have not yet been elucidated in human. Due to the reversible character of their status, prediabetic individuals are of particular interest for preventing the development of type 2 diabetes. The present study is the first to investigate muscle molecular mechanisms during exercise and glucose metabolism after exercise in prediabetic and healthy subjects exercising in normoxia and normobaric hypoxia.

Validation of a Noninvasive Assessment of Pulmonary Gas Exchange During Exercise in Hypoxia

Pulmonary gas exchange efficiency, determined by the alveolar-to-arterial Po2 difference (A-aDo2), progressively worsens during exercise at sea-level; this response is further elevated during exercise in hypoxia. Traditionally, pulmonary gas exchange efficiency is assessed through measurements of ventilation and end-tidal gases paired with direct arterial blood gas (ABG) sampling. Because these measures have a number of caveats, particularly invasive blood sampling, the development of new approaches for the noninvasive assessment of pulmonary gas exchange is needed. Is a noninvasive method of assessing pulmonary gas exchange valid during rest and exercise in acute hypoxia? Twenty-five healthy participants (10 female) completed a staged maximal exercise test on a cycle ergometer in a hypoxic chamber (Fio2= 0.11). Simultaneous ABGs via a radial arterial catheter and noninvasive gas-exchange measurements (AGM100) were obtained in 2-minute intervals. Noninvasive gas exchange, termed the O2 deficit, was calculated from the difference between the end-tidal and the calculated Pao2 (via pulse oximetry and corrected for the Bohr effect by using the end-tidal Pco2). Noninvasive O2 deficit was compared with the traditional alveolar to arterial oxygen difference (A-aDo2), using the traditional Riley analysis. Under conditions of rest at room air, hypoxic rest, and hypoxic exercise, strong correlations between the calculated gPao2 and directly measured Pao2 (R2= 0.97; P< .001; mean bias= 1.70mmHg) were observed. At hypoxic rest and exercise, strong relationships between the estimated and directly measured Pao2 (R2= 0.68; P< .001; mean bias= 1.01mmHg) and O2 deficit with the traditional A-aDo2 (R2= 0.70; P< .001; mean bias= 5.24mmHg) remained. Our findings support the use of a noninvasive measure of gas exchange during acute hypoxic exercise in heathy humans. Further studies are required to determine whether this approach can be used clinically as a tool during normoxic exercise in patients with preexisting impairments in gas exchange efficiency.

Resting Heart Rate Variability at Sea Level Predicts Arterial Desaturation during Acute Exercise in Hypoxia

Predicting responses to acute hypoxia based on physiologic measures at sea level may be valuable in anticipating adverse responses to acute hypoxia. The purpose of this study was to examine the relationships between heart rate variability (HRV) and arterial oxygen desaturation in response to acute hypoxia exposure at rest and during exercise.METHODS13 subjects (6 male, 7 female) aged 20.6±0.3 years rested in a supine position for 10 min. Average resting HRV and arterial oxygen saturation (%SpO2) were calculated from the last 5 min. A VO2peak test to determine aerobic fitness (44.1±3.0 ml/kg/min) was performed on a stationary cycle at sea level. Subjects also performed a submaximal bike test for 10–15 min at 65% of HRmax achieved during the VO2peak test in normobaric hypoxia equivalent to an altitude of 3500 meters.RESULTSHRV (RMSSD 54.5±5.7) was significantly correlated (r=0.227, P&lt;0.05) to the percent change (9.7±0.7) in %SpO2 from rest (97.4±0.2) to exercise (88.0±0.8) in normobaric hypoxia.CONCLUSIONSHRV at rest appears to be predictive of the degree of arterial desaturation during exercise in hypoxia equivalent to an altitude of 3500 meters. Current wearable technology that can measure HRV could be used to predict potential adverse responses to exercise in hypoxic conditions such as altitude.Support or Funding InformationThe Doug Morton/Marilyn Brown Endowment for Biomedical Research, The Foundation for Aging Studies and Exercise Science Research, and The Borgenicht Program.

Nrf2 Activation Enhances Muscular MCT1 Expression and Hypoxic Exercise Capacity.

Skeletal muscle is the major producing and metabolizing site of lactic acid. A family of monocarboxylate transporter (MCT) proteins, especially MCT1 and MCT4, are involved in the lactate-pyruvate exchange and metabolism. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal coordinator of antioxidant response and energy metabolism, and has been reported to associate with the physiological functions of the skeletal muscle. In this study, C57BL/6 J mice were administrated with an Nrf2 activator, sulforaphane (SFN) before taking incremental treadmill exercise to exhaustion under hypoxia; then the effects of SFN on exercise endurance and molecular/biochemical makers of the skeletal muscle were evaluated. The results indicated that SFN pretreatment enhanced the exercise endurance under hypoxia. SFN not only increased the expressions of antioxidant genes and activity of antioxidant enzymes, but also significantly increased the mRNA and protein levels of MCT1 and CD147, but not MCT4. Moreover, the expressions of LDH-B and LDH activity of converting lactate into pyruvate, as well as citrate synthase activity were significantly higher, whereas the LDH activity of converting pyruvate into lactate and blood lactate level were remarkably lower in the SFN-exercise mice than those of the phosphate-buffered saline-exercise group. Furthermore, Atf3Δzip2 (the alternatively spliced isoform of activating transcription factor-3) mRNA was increased by the exercise and further potentiated by SFN. These results show, for the first time, that SFN increases MCT1 expression in the skeletal muscle under acute hypoxic exercise and suggest that Nrf2 activation is a promising strategy to enhance exercise performance under hypoxia.

Influence of high affinity haemoglobin on the response to normoxic and hypoxic exercise.

Theoretical models suggest there is no benefit of high affinity haemoglobin to preserve maximal oxygen uptake in acute hypoxia but the comparative biology literature has many examples of species that are evolutionarily adapted to hypoxia and have high affinity haemoglobin. We studied humans with high affinity haemoglobin and compensatory polycythaemia. These subjects performed maximal exercise tests in normoxia and hypoxia to determine how their altered haemoglobin affinity impacts hypoxic exercise tolerance. The high affinity haemoglobin participants demonstrated an attenuated decline in maximal aerobic capacity in acute hypoxia. Those with high affinity haemoglobin had no worsening of pulmonary gas exchange during hypoxic exercise but had greater lactate and lower pH than controls for all exercise bouts. High affinity haemoglobin and compensatory polycythaemia mitigated the decline in exercise performance in acute hypoxia through a higher arterial oxygen content and an unchanged pulmonary gas exchange. The longstanding dogma is that humans exhibit an acute reduction in haemoglobin (Hb) binding affinity for oxygen that facilitates adaptation to moderate hypoxia. However, many animals have adapted to high altitude through enhanced Hb binding affinity for oxygen. The objective of the study was to determine whether high affinity haemoglobin (HAH) affects maximal and submaximal exercise capacity. To accomplish this, we recruited individuals (n=11, n=8 females) with HAH (P50 =16±1mmHg), had them perform normoxic and acute hypoxic (15% inspired oxygen) maximal exercise tests, and then compared their results to matched controls (P50 =26±1, n=14, n=8 females). Cardiorespiratory and arterial blood gases were collected throughout both exercise tests. Despite no difference in end-exercise arterial oxygen tension in hypoxia (59±6 vs. 59±9mmHg for controls and HAH, respectively), the HAH subjects' oxyhaemoglobin saturation ( ) was ∼7% higher. Those with HAH had an attenuated decline in maximal oxygen uptake ( ) (4±5% vs. 12±%, p<0.001) in hypoxia and the change in between trials was related to the change in (r=-0.75, p<0.0001). Compared to normoxia, the controls' alveolar-to-arterial oxygen gradient significantly increased during hypoxic exercise, whereas pulmonary gas exchange in HAH subjects was unchanged between the two exercise trials. However, arterial lactate was significantly higher and arterial pH significantly lower in the HAH subjects for both exercise trials. We conclude that HAH attenuates the decline in maximal aerobic capacity and preserves pulmonary gas exchange during acute hypoxic exercise. Our data support the comparative biology literature indicating that HAH is a positive adaptation to acute hypoxia.

Altered Hemorheology in Fontan Patients in Normoxia and After Acute Hypoxic Exercise

BackgroundThe Fontan circulation is a unique palliation procedure for several congenital heart defects. Impaired exercise capacity has previously been demonstrated in these patients and also a higher risk for cardiopulmonary mortality. Hemorheology was shown to affect cardiopulmonary capacity and in turn to be affected by regular exercise and hypoxia but none of these have been investigated in Fontan patients so far. The aim of this study was to detect general differences in hemorheology in normoxia as well as possible altered hemorheological responses to hypoxia exposure and hypoxic exercise between Fontan patients and healthy controls.Methods and Findings26 Fontan patients and 20 healthy controls performed an acute exercise test (AET) on a bicycle ergometer under hypoxia with ambient 15.2% oxygen saturation (sO2). Blood samples were taken at rest in normoxia (T0), at rest in hypoxia (T1), after maximum exhaustion in hypoxia (T2), and after 50 min recovery in normoxia (T3). Hemorheological and blood parameters were investigated. Additionally, arterial stiffness was tested at T0. Red blood cell (RBC) deformability, NOx, erythropoietin (EPO) concentration, RBC count, hemoglobin (Hb) concentration and hematocrit (hct) were significantly increased in Fontan patients compared to controls. Same was observed for arterial stiffness. No changes were observed for RBC aggregation, fibrinogen concentration, free radical levels and vascular endothelial growth factor (VEGF). Hypoxia exposure did not change parameters, whereas exercise in hypoxia increased aggregation and hct significantly in both groups. Fontan patients showed significantly increased aggregation-disaggregation balance compared to controls.ConclusionAcute hypoxia exposure and exercise under hypoxia might have similar impact on hemorheology in Fontan patients and controls and was clinically well tolerated. Nevertheless, exercise alters aggregation and possibly hemodynamics which requires special attention in Fontan patients.

TRPV4 plays an important role in rat prefrontal cortex changes induced by acute hypoxic exercise.

ObjectiveThis study aims to investigate the effects of TRPV4 on acute hypoxic exercise-induced central fatigue, in order to explore the mechanism in central for exercise capacity decline of athletes in the early stage of altitude training.Methods120 male Wistar rats were randomly divided into 12 groups: 4 normoxia groups (quiet group, 5-level group, 8-level group, exhausted group), 4 groups at simulated 2500 m altitude (grouping as before), 4 groups at simulated 4500 m altitude (grouping as before), 10 in each group. With incremental load movement, materials were drawn corresponding to the load. Intracellular calcium ion concentration was measured by HE staining, enzyme-linked immunosorbent assay, immunohistochemistry, RT-qPCR, Fluo-4/AM and Fura-2/AM fluorescence staining.Results(1) Hypoxic 2–5 groups showed obvious venous congestion, with symptoms similar to normoxia-8 group; Hypoxic 2–8 groups showed meningeal loosening edema, infra-meningeal venous congestion, with symptoms similar to normoxia-exhausted group and hypoxic 1-exhaused group. (2) For 5,6-EET, regardless of normoxic or hypoxic environment, significant or very significant differences existed between each exercise load group (normoxic − 5 level 20.58 ± 0.66 pg/mL, normoxic − 8 level 23.15 ± 0.46 pg/mL, normoxic - exhausted 26.66 ± 0.71 pg/mL; hypoxic1-5 level 21.72 ± 0.43 pg/mL, hypoxic1-8 level 24.73 ± 0.69 pg/mL, hypoxic 1-exhausted 28.68 ± 0.48 pg/mL; hypoxic2-5 level 22.75 ± 0.20 pg/mL, hypoxic2-8 level 25.62 ± 0.39 pg/mL, hypoxic 2-exhausted 31.03 ± 0.41 pg/mL) and quiet group in the same environment(normoxic-quiet 18.12 ± 0.65 pg/mL, hypoxic 1-quiet 19.94 ± 0.43 pg/mL, hypoxic 2-quiet 21.72 ± 0.50 pg/mL). The 5,6-EET level was significantly or extremely significantly increased in hypoxic 1 environment and hypoxic 2 environment compared with normoxic environment under the same load. (3) With the increase of exercise load, expression of TRPV4 in the rat prefrontal cortex was significantly increased; hypoxic exercise groups showed significantly higher TRPV4 expression than the normoxic group. (4) Calcium ion concentration results showed that in the three environments, 8 level group (normoxic-8 190.93 ± 6.11 nmol/L, hypoxic1-8 208.92 ± 6.20 nmol/L, hypoxic2-8 219.13 ± 4.57 nmol/L) showed very significant higher concentration compared to quiet state in the same environment (normoxic-quiet 107.11 ± 0.49 nmol/L, hypoxic 1-quiet 128.48 ± 1.51 nmol/L, hypoxic 2-quiet 171.71 ± 0.84 nmol/L), and the exhausted group in the same environment (normoxic-exhausted 172.51 ± 3.30 nmol/L, hypoxic 1-exhausted 164.54 ± 6.01 nmol/L, hypoxic 2-exhausted 154.52 ± 1.80 nmol/L) had significant lower concentration than 8-level group; hypoxic2-8 had significant higher concentration than normoxic-8.ConclusionAcute hypoxic exercise increases the expression of TRPV4 channel in the prefrontal cortex of the brain. For a lower ambient oxygen concentration, expression of TRPV4 channel is higher, suggesting that TRPV4 channel may be one important mechanism involved in calcium overload in acute hypoxic exercise.

Downhill Running: An Effective Countermeasure To Limitations Of Exercise In Acute Hypoxia?

Exercise stress that results in increased expression of heat shock protein 72 (Hsp72) is linked to physiologic adaptations. Adaptations to one environmental stressor, such as heat, increase Hsp72 and induce cross adaptations to other stressors (i.e. hypoxia). Previously, two bouts of downhill running (DHR) conferred classic markers of heat acclimation (lower Tc, earlier onset of sweating). We sought to increase Hsp72 through repeated DHR to potentially expedite the acclimation process. PURPOSE: To analyze the effect of DHR on exercise performance in normobaric hypoxia. METHODS: 8 males (23.8 ± 5.8 years, VO2max 54.1 ± 5.1 ml kg-1 min-1, 13.6 ± 5.2% body fat) performed two 45-minute DHR bouts (-12.5% grade) separated by 5-7 days in the speed that elicited VT while running downhill. Pre and post blood samples were collected to quantify monocyte Hsp72. Muscle soreness (DOMS) was assessed 24 and 48 hours after each downhill bout using a Likert scale. Two normobaric hypoxic (16% FiO2) 5 km time trials (TT) were performed: one before any DHR and one 5-7 days after the last bout. Hydration was assessed before the TT while blood lactate was measured pre and post TT. During the TT, heart rate, RPE and O2 saturation (SaO2) were recorded every 1 km. RESULTS: Monocyte Hsp72 showed no change across time (p=0.53). Specifically, basal concentration from DHR I to DHR II were not different (3.5 ± 2.3 to 2.9 ± 1.5 AU). TT performance was similar between conditions (1377 ± 192 ; 1364 ± 174 sec). Hydration (1.018 ± 0.007; 1.013 ± 0.009 urine specific gravity), RPE (14.9 ± 1.1; 14.6 ± 1.3), HR (178 ± 8;178 ± 8), and blood lactate (post TT1 11.6 ± 1.8; post TT2 12.0 ± 3.1 mM) were similar in both TTs. However, SaO2 significantly increased from TT1 to TT2 (84.5 ± 4.0; 87.2 ± 2.3%, p<0.05). DOMS was significantly lowered 24 (5.1 ± 0.8 to 3.5 ± 1.4, p = 0.00) and 48 (4.6 ± 1.0 to 2.6 ± 1.5, p = 0.00) hours following the second DHR trial when compared to the first trial. CONCLUSIONS: While no change in Hsp72 or TT time were observed, this could be due to large variations found in the data with these variables. The increase in SaO2 after DHR may improve exercise capacity at elevation during moderate exercise intensities.

Metabolomic Response to Acute Hypoxic Exercise and Recovery in Adult Males.

Metabolomics is a relatively new “omics” approach used to characterize metabolites in a biological system at baseline and following a diversity of stimuli. However, the metabolomic response to exercise in hypoxia currently remains unknown. To examine this, 24 male participants completed 1 h of exercise at a workload corresponding to 75% of pre-determined O2max in hypoxia (Fio2 = 0.16%), and repeated in normoxia (Fio2 = 0.21%), while pre- and post-exercise and 3 h post-exercise metabolites were analyzed using a LC ESI-qTOF-MS untargeted metabolomics approach in serum samples. Exercise in hypoxia and in normoxia independently increased metabolism as shown by a change in a combination of twenty-two metabolites associated with lipid metabolism (p < 0.05, pre vs. post-exercise), though hypoxia per se did not induce a greater metabolic change when compared with normoxia (p > 0.05). Recovery from exercise in hypoxia independently decreased seventeen metabolites associated with lipid metabolism (p < 0.05, post vs. 3 h post-exercise), compared with twenty-two metabolites in normoxia (p < 0.05, post vs. 3 h post-exercise). Twenty-six metabolites were identified as responders to exercise and recovery (pooled hypoxia and normoxia pre vs. recovery, p < 0.05), including metabolites associated with purine metabolism (adenine, adenosine and hypoxanthine), the amino acid phenylalanine, and several acylcarnitine molecules. Our novel data provides preliminary evidence of subtle metabolic differences to exercise and recovery in hypoxia and normoxia. Specifically, exercise in hypoxia activates metabolic pathways aligned to purine and lipid metabolism, but this effect is not selectively different from exercise in normoxia. We also show that exercise per se can activate pathways associated with lipid, protein and purine nucleotide metabolism.

PO-156 Effects of acute hypoxic exercise on TRPV4 channels in prefrontal cortex of rats

Objective At the early stage of high altitude training, the decrease of motor ability caused by hypoxia makes it impossible for the training to be carried out normally. Since 90s, researchers have focused more on the decrease of the cardiopulmonary function and muscle oxygen utilization capacity, but there are few studies on cerebral hemodynamic factors, and no related mechanism studies. This study will take this as a starting point, to study the acute hypoxic exercise and its biological mechanism for brain hemodynamic effects of prefrontal cortex, providing a new target in order to improve the athletes at the beginning of the plateau duration and decreased exercise capacity problems.&#x0D; Methods In order to explore the changes of the TRPV4 channels protein in rat prefrontal cortex induced by exercise under hypoxic exposure, this study used HE staining and immunohistochemical method to analyze the pathological changes and TRPV4 channel protein expression of prefrontal cortex in rats during incremental exercise in different oxygen concentration environment. &#x0D; Results The results showed that cortex lesions characterized by venous congestion and neuronophagia, when exercise to level 5 under the condition of the simulated 4500 meters altitude, which was similar to normoxia exercise to level 8. With the increasing of exercise load, the expressions of TRPV4 in rat prefrontal cortex were significantly increased. And the TRPV4 expressions of every groups in the simulated 4500 meters altitude were significantly higher than those in normoxia groups. &#x0D; Conclusions The results indicate that increased load exercise in acute hypoxia can lead to pathological changes of brain tissue much earlier that in normoxia condition, and increase the expression of TRPV4 channel protein in brain tissue. This study will provide valuable data for the study of the role of Ca2+ channels in the membrane of central nervous system in the phenomenon of the centers fatigue appearing earlier in hypoxic exercise.

PO-142 Effects of hypoxia preconditioning on acute hypoxic exercise-induced phosphorylation of AMPKα in mice skeletal muscle

Objective AMP-activated protein kinase (AMPK) is a metabolic energy sensor and its activation plays an important role in the regulation of energy homeostasis. Increasing evidence indicates that AMPK activation depend on the phosphorylation sites in AMPKα. Thr172 is involved in AMPK activation, whereas Ser485/491 are not. Under suitable stress stimulations, the phosphorylation of AMPKα at the Thr172 site can increase AMPK activation. However, serious hypoxic exercise or taking antioxidants before exercise can reduce the activation of AMPK by phosphorylating AMPK α1Ser485/α2Ser491 sites. The aim of this study was to investigate the effects of hypoxia preconditioning on exhaustive exercise under hypoxic condition induced AMPKα Thr172 and Ser485/491 phosphorylation in mice skeletal muscle.&#x0D; Methods The 40 eight-week-old male C57BL/6J wild type mice were randomly divided into four groups (10 mice /group): non-hypoxia preconditioning control group (NC), hypoxia preconditioning control group (HC), non-hypoxia preconditioning acute hypoxic exercise group (NE), and hypoxia preconditioning acute hypoxic exercise group (HE). Hypoxia preconditioning groups were exposure in hypoxia for 48h, with the oxygen concentration was 11.2%. Meanwhile, non-hypoxia preconditioning was in the normoxic condition for 48h. After hypoxia preconditioning, acute hypoxic exercise groups finished an exhaustive exercise. Tibialis anterior muscles of mice were collected immediately after the exhaustive exercise. The protein expression of the total AMPKα, Thr172-AMPKα phosphorylation, and Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation were measured by Western Blot. Thr172-AMPKα phosphorylation to total AMPKα ratio and Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation to total AMPKα ratio was calculated.&#x0D; Results Compared with NE group, The Thr172-AMPKα phosphorylation to total AMPKα ratio was increased significantly, whereas the relative expression of Ser485-AMPKα1/Ser491-AMPKα2 phosphorylation to total AMPKα ratio seemed to decreased in skeletal muscle of HE group.&#x0D; Conclusions The 48h hypoxia preconditioning could improve the AMPK activation by Thr172-AMPKα phosphorylation in mice skeletal muscle following an exhaustive exercise under the hypoxic condition.

Dynamics of blood lactate concentration during recovery period of short duration‐high intensity exercise in acute hypoxia or normoxia

We studied dynamics of blood lactate concentration during recovery period of short duration‐high intensity exercise in acute hypoxia or normoxia. University track and field athletes were recruited for single‐blind randomized crossover designed study. All subjects completed wingate test in both acute hypoxia (FiO2=0.145) and normoxia (FiO2=0.21). Two wingate tests were separated at least 48 hours. After 10 min cycling warm‐up (100 W), subjects took 5 min rests and then conducted 30 sec wingate tests. After the wingate test, subjects of both conditions took 30 min rests in normoxia. Blood samplings were conducted 1 min before and, 0.5, 1, 2, 3, 4, 5, 7, 10, 20 and 30 min after the wingate tests to examine the blood lactate concentration. Peak power output (PPO), mean power output (MPO) and fatigue index (FI) were not different in both condition (PPO; 984.3±49.3 W and 971.0±32.1 W, MPO; 674.3±37.4 W and 680.0±36.3 W, FI; 49.2±7.1% and 49.6±5.2%, normoxia and hypoxia respectively). The AUC of blood lactate, when examined pre to 10 min values, was significantly higher in acute hypoxia than normoxia (p&lt;0.05). The rates of reduction of blood lactate concentration was higher in hypoxia than normoxia(p&lt;0.05, 0.42±0.02 and 0.28±0.03 mmol/L/min, respectively). These results suggested that muscle glycogen breakdown was higher in acute hypoxia than normoxia in spite of same wingate test performances. It also suggests that lactate oxidation may be higher in acute hypoxic group when resting at normoxia.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.