Moderate Hypoxia Research Articles

Effects of Acute Moderate Hypoxia versus Normoxia on Metabolic and Cardiac Function and Skeletal Muscle Oxygenation during Endurance Exercise at the Same Heart Rate Level.

This study aimed to investigate the effects of acute moderate hypoxia (HYP), compared with those of normoxia (NORM), during endurance exercise with the same HR level on metabolic function, skeletal muscle oxygenation, and cardiac function. Twelve healthy men (aged 25.1 ± 2.3 years) completed 30 min of endurance exercise using a cycle ergometer with the same HR level (136.5 ± 1.5 bpm) corresponding to 70% maximal heart rate (HRmax) under NORM (760 mmHg) and HYP (526 mmHg, simulated 3000 m altitude) after a 30 min exposure in the respective environments on different days, in random order. Exercise load, rating of perceived exertion (RPE), metabolic function (saturation of percutaneous oxygen; SpO2, minute ventilation; oxygen uptake; VO2, carbon dioxide excretion; respiratory exchange ratio; RER, and oxygen pulse), skeletal muscle oxygen profiles (oxyhemoglobin, oxhb, deoxyhemoglobin, dxhb, total hemoglobin, and tissue oxygenation index; StO2), and cardiac function (heart rate, stroke volume, cardiac output, end-diastolic volume, end-systolic volume, and ejection fraction) were measured during endurance exercise. HYP showed a lower exercise load with the same RPE during exercise than did NORM. In addition, HYP showed a lower SpO2, VO2, oxygen pulse, oxhb, and StO2, and a higher RER and dxhb during exercise than NORM. We found that HYP showed lower exercise load and VO2 at the same RPE than NORM and also confirmed a higher anaerobic metabolism and oxygen inflow into skeletal muscle tissue due to the limitation of oxygen delivery capacity.

Fipronil impairs the GABAergic brain responses of Nile Tilapia during the transition from normoxia to acute hypoxia.

γ-aminobutyric acid (GABA) is one of the main neurotransmitters involved in the adaptation processes against the damage that hypoxia can cause to the brain. Due to its antagonist action on GABA receptors, the insecticide fipronil can turn the fish more susceptible to the negative effects of hypoxia. This study aimed to understand better if fipronil affects these GABAergic responses of Tilapia ahead to hypoxia. Oreochromis Niloticus (Nile Tilapia) were exposed for 3 and 8 h to fipronil (0.0, 0.1, and 0.5 µg.L-1 ) under normoxia (dissolved O2 > 6 mg.L-1 ) and moderate hypoxia (dissolved O2 < 2 mg.L-1 ) conditions. Briefly, hypoxia caused opposite effects on the gene transcription of the evaluated ionotropic and metabotropic GABA receptors. Unexpectedly, we obtained reduced HIF1A mRNA and brain GABA levels, mostly in the first 3 h of the experiment, for the hypoxic group compared with the normoxia one. Besides that, we also demonstrated that the insecticide fipronil impairs the brain GABAergic signaling of a hypoxia-tolerant fish during the transition from a normoxic to an acute hypoxic state. Thus, these results predict the relevant impact on the brain metabolic adaptations of fishes exposed to such stressful conditions in an aquatic environment, as well as the effects of fipronil in the GABAergic responses to hypoxia, which in turn may have ecological and physiological significance to hypoxia-tolerant fishes exposed to this insecticide.

Heart rate variability, task load and perceived exertion associated with a long-distance military ski exercise: A pilot study

Objectives: Skiing is practiced by the security forces posted at mountain areas for patrolling, securing borders, taking up rescue missions and sometimes as recreational activities. A study was planned to assess physiological and mental stress of a military ski activity through the measurement of heart rate (HR) variability, task load and perceived exertion. Materials and Methods: Eleven healthy Indian soldiers, trained with skiing techniques, participated in a 15 km skiing with 22 kg equipment at a predetermined snowy mountainous track. Pre- and post-exercise HR and HR variability (HRV) were recorded (bio-harness, Zephyr, USA) and questionnaires, namely NASA task load index (NASA-TLX) and Borg’s rating of perceived exertion (RPE) scale, were filled after exercise. Time and frequency domain parameters such as HR, variations between successive RR intervals (RMSSD), standard deviation of RR (SDNN) and percentage value of NN50 (pNN50), low- and high-frequency bands (LF and HF %) and LF/HF ratio were derived using Kubios software. Student’s t (paired) test was applied to compare pre- and post-exercise HRV parameters and Pearson’s correlation was applied to observe interdependencies between HRV and subjective scores. Results: The findings depicted increase in post-exercise HR and decrease in overall HRV (both significant). Besides this, there was an increase in LF (significant) and LF/HF ratio (insignificant). Such response shows sympathetic dominance over parasympathetic domain of autonomic nervous system. The physical and mental stress experienced during the exercise was also expressed through high physical demand (79 out of 100) and high overall task load (total score – 77 out of 100) of the NASA-TLX and a moderately heavy RPE score (14 out of 20). Conclusion: The pre- and post-exercise differences in physiological variables ensured the presence of physical stress along with dominance of sympathetic nervous system. Overall task load was depicted with high subjective ratings. Carrying out skiing task in an environment infested with cold, wind chill, moderate hypoxia at a snowy and mountainous track possibly has induced the observed physiological and mental stress to the participants. Such findings are important to understand exact requirements of the mountain warfare events carried out by the forces.

Tissue origin of circulating microRNAs and their response to nutritional and environmental stress in rainbow trout (Oncorhynchus mykiss)

Stresses associated with changes in diet or environmental disturbances are common situations that fish encounter during their lifetime. The stability and ease of measuring microRNAs (miRNAs) present in biological fluids make these molecules particularly interesting biomarkers for non-lethal assessment of stress in animals.Rainbow trout were exposed for four weeks to abiotic stress (moderate hypoxia) and/or nutritional stress (a high-carbohydrate/low-protein diet). Blood plasma and epidermal mucus were sampled at the end of the experiment, and miRNAs were assessed using small RNA sequencing. We identified four miRNAs (miR-122-5p, miR-184-3p, miR-192-5p and miR-194a-5p) and three miRNAs (miR-210-3p, miR-153a-3p and miR-218c-5p) that accumulated in response to stress in blood plasma and epidermal mucus, respectively. In particular, the abundance of miR-210-3p, a hypoxamiR in mammals, increased strongly in the epidermal mucus of rainbow trout subjected to moderate hypoxia, and can thus be considered a relevant biomarker of hypoxic stress in trout. We explored the contribution of 22 tissues/organs to the abundance of circulating miRNAs (c-miRNAs) in blood plasma and epidermal mucus influenced by the treatments. Some miRNAs were tissue-specific, while others were distributed among several tissues. Some c-miRNAs (e.g., miR-210-3p, miR184-3p) showed similar variations in both tissues and fluids, while others showed an inverse trend (e.g., miR-122-5p) or no apparent relationship (e.g. miR-192-5p, miR-194a-5p.Overall, these results demonstrate that c-miRNAs can be used as non-lethal biomarkers to study stress in fish. In particular, the upregulation of miR-210-3p in epidermal mucus induced by hypoxia demonstrates the potential of using epidermal mucus as a matrix for identifying non-invasive biomarkers of stress. This study provides information about the tissue sources of c-miRNAs and highlights the potential difficulty in relating variations in miRNA abundance in biological fluids to that in tissues.

Sex-specific effects of chronic hypoxia on routine cardiovascular function and metabolism in CD-1 mice.

Hypoxia can have significant impacts on cardiovascular physiology, but the effects of chronic exposure to moderate hypoxia and how they differ between sexes remain poorly understood. We used physiological telemetry to examine this issue in CD-1 mice. Adult mice were chronically exposed to normoxia or hypobaric hypoxia (12 kPa O2) for 6 wk and then subjected to telemetry measurements of routine physiology across the diel cycle. Heart rate (fH), mean arterial blood pressure (Pmean), body temperature (Tb), and activity were greater during the nighttime active phase than the daytime inactive phase. Chronic hypoxia had no effect on these traits at night but had sex-specific effects during the day, when chronic hypoxia reduced fH, Tb, and activity in males but not females. These differences existed without any effect of chronic hypoxia on α-adrenergic or nitric oxide tone on the vasculature (assessed as Pmean response to pharmacological blockade). Responses to acute hypoxia were then measured during stepwise reductions in inspired O2 from 21 to 8 kPa O2. O2 consumption rate, fH, Pmean, and Tb declined in severe hypoxia, but the O2 tension at which this began was lower in mice held in chronic hypoxia. However, the hypoxic ventilatory response was augmented by exposure to chronic hypoxia in females but not in males. Females also exhibited larger increases in lung mass and less right ventricle hypertrophy than males in chronic hypoxia. Our results support the growing evidence that there can be considerable sex differences in the cardiorespiratory responses to hypoxia.

Correlation Analysis of Early Renal Injury in Elderly Patients with Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

ObjectiveTo investigate the correlation between serum cystatin C (Cys-C) and beta-2 (β2) microglobulin (β2-MG) levels and renal injury in elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with a view to detecting renal injury in its early stages.MethodsA total of 106 patients with AECOPD were enrolled and divided into three groups according to their oxygen partial pressure (PO2) levels: severe hypoxia group, moderate hypoxia group, and mild hypoxia group. Another 60 healthy subjects were selected as the control group. General clinical data were collected from all the study subjects, along with measurements of arterial blood gas, Cys-C, β2-MG, serum creatinine (Scr), urea nitrogen (BUN), partial pressure of carbon dioxide (PCO2), and high-sensitivity C-reactive protein (hs-CRP).ResultsThe levels of hs-CRP, Cys-C, β2-MG, Scr, and BUN were highest in the severe hypoxia group, followed by the moderate hypoxia group, then the mild hypoxia group, and lowest in the control group. The differences between the groups were statistically significant for these indicators (P < 0.05). Apart from in the cases of Scr and BUN, there were no statistically significant differences between the mild group and the control group (P > 0.05). The levels of Cys-C and β2-MG were positively correlated with the levels of hs-CRP, PCO2, Scr, and BUN and negatively correlated with PO2 levels. hs-CRP and PO2 were high-risk factors influencing Cys-C levels, and β2-MG was a risk factor influencing Cys-C levels. The level of PO2 was a high-risk factor influencing β2-MG levels, and PCO2 and Cys-C were risk factors influencing β2-MG levels.ConclusionRenal injury was found to be present in patients with AECOPD and worsened with increasing degrees of hypoxia. Hypoxia and inflammation might be risk factors for renal injury in patients with AECOPD, Cys-C and β2-MG could be sensitive indicators for the early detection of renal injury.

Influence of exercise intensity and hypoxic exposure on physiological, perceptual and biomechanical responses to treadmill running

ABSTRACT Acute physiological, perceptual and biomechanical consequences of manipulating both exercise intensity and hypoxic exposure during treadmill running were determined. On separate days, eleven trained individuals ran for 45 s (separated by 135 s of rest) on an instrumented treadmill at seven running speeds (8, 10, 12, 14, 16, 18 and 20 km.h−1) in normoxia (NM, FiO2 = 20.9%), moderate hypoxia (MH, FiO2 = 16.1%), high hypoxia (HH, FiO2 = 14.1%) and severe hypoxia (SH, FiO2 = 13.0%). Running mechanics were collected over 20 consecutive steps (i.e. after running ∼25 s), with concurrent assessment of physiological (heart rate and arterial oxygen saturation) and perceptual (overall perceived discomfort, difficulty breathing and leg discomfort) responses. Two-way repeated-measures ANOVA (seven speeds × four conditions) were used. There was a speed × condition interaction for heart rate (p = 0.045, ηp2 = 0.22), with lower values in NM, MH and HH compared to SH at 8 km.h−1 (125 ± 12, 125 ± 11, 128 ± 12 vs 132 ± 10 b.min−1). Overall perceived discomfort (8 and 16 km.h−1; p = 0.019 and p = 0.007, ηp2 = 0.21, respectively) and perceived difficulty breathing (all speeds; p = 0.023, ηp2 = 0.37) were greater in SH compared to MH, whereas leg discomfort was not influenced by hypoxic exposure. Minimal difference was observed in the twelve kinetics/kinematics variables with hypoxia (p > 0.122; ηp 2 = 0.19). Running at slower speeds in combination with severe hypoxia elevates physiological and perceptual responses without a corresponding increase in ground reaction forces. Highlights The extent to which manipulating hypoxia severity (between normoxia and severe hypoxia) and running speed (from 8 to 20 km.h−1) influence acute physiological and perceptual responses, as well as kinetic and kinematic adjustments during treadmill running was determined. Running at slower speeds in combination with severe hypoxia elevates heart rate, while this effect was not apparent at faster speeds. Arterial oxygen saturation was increasingly lower as running speed and hypoxic severity increased. Overall perceived discomfort (8 and 16 km.h−1) and perceived difficulty breathing (all speeds) were lower in moderate hypoxia than in severe hypoxia, whereas leg discomfort remained unchanged with hypoxic exposure.

Cellular composition of the black scorpionfish (Scorpaena porcus, L 1758) blood and head kidney under short-time acute exposure to hypoxia.

In the present work, we studied the effect of short-term acute hypoxia on the cellular composition of the blood and the head kidney of the black scorpionfish. Dissolved oxygen concentration was decreased from 8.5-8.7mg O2 l-1 (normoxia) to 3-5mg O2 l-1 (relative normoxia), 1-3mg O2 l-1 (moderate hypoxia), and 0-1mg O2 l-1 (acute hypoxia) within 1.5-2h by bubbling of water with N2. Exposure period was 4h, water temperature was adjusted to 14-16°C, and photoperiod was 12h (light). Short-time acute hypoxia induced a rapid release of blast and immature cells from the head kidney into the circulating blood of the black scorpionfish, which was associated with reduction in erythropoietic reserves in 2.5 times. The number of immature erythroid cells (pronormoblasts, basophilic and polychromatophilic normoblasts) significantly increased in blood, and the simultaneously relative decrease of the number of abnormal red blood cell (RBC) and the increase of the number of RBC ghosts (lysed RBCs) in circulating blood were observed. The significant correlation between methemoglobin concentration and the number of RBC ghosts was shown (R2 = 0.640 or r = 0.800). Hypoxia induced RBC swelling on 5-6% compared to control. The number of RBC ghosts in the blood is likely involved in the stimulation of erythropoietin production under hypoxia.

UCP2 modulates cardiomyocyte cell cycle activity, acetyl-CoA, and histone acetylation in response to moderate hypoxia.

Developmental cardiac tissue is regenerative while operating under low oxygen. After birth, ambient oxygen is associated with cardiomyocyte cell cycle exit and regeneration. Likewise, cardiac metabolism undergoes a shift with cardiac maturation. Whether there are common regulators of cardiomyocyte cell cycle linking metabolism to oxygen tension remains unknown. The objective of the study is to determine whether mitochondrial UCP2 is a metabolic oxygen sensor regulating cardiomyocyte cell cycle. Neonatal rat ventricular myocytes (NRVMs) under moderate hypoxia showed increased cell cycle activity and UCP2 expression. NRVMs exhibited a metabolic shift toward glycolysis, reducing citrate synthase, mtDNA, mitochondrial membrane potential (ΔΨm), and DNA damage/oxidative stress, while loss of UCP2 reversed this phenotype. Next, WT and mice from a global UCP2-KO mouse line (UCP2KO) kept under hypoxia for 4 weeks showed significant decline in cardiac function that was more pronounced in UCP2KO animals. Cardiomyocyte cell cycle activity was reduced, while fibrosis and DNA damage was significantly increased in UCP2KO animals compared with WT under hypoxia. Mechanistically, UCP2 increased acetyl-CoA levels and histone acetylation, and it altered chromatin modifiers linking metabolism to cardiomyocyte cell cycle under hypoxia. Here, we show a potentially novel role for mitochondrial UCP2 as an oxygen sensor regulating cardiomyocyte cell cycle activity, acetyl-CoA levels, and histone acetylation in response to moderate hypoxia.

How does multi-set high-load resistance exercise impact neuromuscular function in normoxia and hypoxia?

ABSTRACT This study examined whether hypoxia during multi-set, high-load resistance exercise alters neuromuscular responses. Using a single-blinded (participants), randomised crossover design, eight resistance-trained males completed five sets of five repetitions of bench press at 80% of one repetition maximum in moderate normobaric hypoxia (inspiratory oxygen fraction = 0.145) and normoxia. Maximal isometric bench press trials were performed following the warm-up, after 10 min of altitude priming and 5 min post-session (outside, inside and outside the chamber, respectively). Force during pre-/post-session maximal voluntary isometric contractions and bar velocity during exercise sets were measured along with surface electromyographic (EMG) activity of the pectoralis major, anterior deltoid and lateral and medial triceps muscles. Two-way repeated measures ANOVA (condition×time) were used. A significant time effect (p = 0.048) was found for mean bar velocity, independent of condition (p = 0.423). During sets of the bench press exercise, surface EMG amplitude of all studied muscles remained unchanged (p > 0.187). During maximal isometric trials, there were no main effects of condition (p > 0.666) or time (p > 0.119), nor were there any significant condition×time interactions for peak or mean forces and surface EMG amplitudes (p > 0.297). Lower end-exercise blood oxygen saturation (90.9 ± 1.8 vs. 98.6 ± 0.6%; p < 0.001) and higher blood lactate concentration (5.8 ± 1.4 vs. 4.4 ± 1.6 mmol/L; p = 0.007) values occurred in hypoxia. Acute delivery of systemic normobaric hypoxia during multi-set, high-load resistance exercise increased metabolic stress. However, only subtle neuromuscular function adjustments occurred with and without hypoxic exposure either during maximal isometric bench press trials before versus after the session or during actual exercise sets. Highlights Performing multi-set, high-load bench press resistance exercise in hypoxia accentuates metabolic stress, as evidenced by lower arterial oxygen saturation and higher blood lactate concentration, compared to normoxia. Acute hypoxic exposure doesn’t alter neuromuscular responses during the execution of the sets since mean bar velocity dropped similarly in both conditions from set 2 to set 5 with no difference in peak velocity and surface EMG amplitude of the prime movers during the bench press. Only subtle adjustments in peak or mean force and accompanying surface EMG activity occur with and without hypoxic exposure during maximal isometric bench press trials after a 10-min hypoxic priming period and 5 min after the session in reference to post-warm-up.

Gill remodeling increases the respiratory surface area of grass carp (Ctenopharyngodon idella) under hypoxic stress

Seasonal changes, diurnal variations, and eutrophication result in periodic hypoxia in fish habitats, thus affecting the success of commercial aquaculture. In this study, the grass carp (Ctenopharyngodon idella) presented moderate hypoxia tolerance; they showed a medium critical oxygen tension during the loss of equilibrium. In response to 7 d of hypoxic exposure, the erythrocyte count and hemoglobin (Hb) concentration significantly increased (p < 0.01). To cope with the hypoxic environment, the grass carp underwent gill remodeling marked by reduction in the interlamellar cell mass (ILCM) and an increase in respiratory surface area. The gill remodeling under hypoxia was enabled by apoptosis induction. Although apoptotic signals were not found on ILCM cells, transferase dUTP nick end labeling (TUNEL) assay results indicated that after 1 d of hypoxic exposure, the number of TUNEL-positive cells per lamella increased until 4 d and then began to decrease. Consistent with the results of the TUNEL assay, the mRNA expression of apoptosis-related genes, caspase-3, Bax, and Bcl-2, increased at 1, 4, and 7 d of the hypoxia treatment. In addition, gill remodeling significantly (p < 0.01) decreased the concentration of sodium and chloride ions in the fish serum. These findings provide evidence that grass carps increase their respiratory surface area through gill remodeling by apoptosis in the gill filaments to acclimate to a hypoxic environment. This study expands our understanding of the morphological and physiological changes in grass carp in response to a hypoxic environment; therefore, it could be useful for maintaining grass carp production.

Assessment of bone mineral density and bone metabolism in young men with obstructive sleep apnea: a cross-sectional study

BackgroundHypoxia in obstructive sleep apnea (OSA) patients during sleep may have an effect on bone metabolism. Few data regarding evaluation of bone metabolism in young individuals diagnosed with OSA. In this study, we aim to identify the association between bone mineral density and OSA in young men (≤ 40 years old of age).MethodsConsecutive male subjects who underwent polysomnography were enrolled. Serum calcium, 25-hydroxyvitamin-D3, β-isomerized form C-terminal telopeptide of type I collagen, osteocalcin and procollagen type 1 N-propeptide were measured in all participants, and bone mineral density (BMD) at lumbar spine (L1-L4), femoral neck and hip total were determined by dual energy X-ray absorption (DXA).ResultsThe population consisted of 85 subjects (mean age 35.53 years). The BMD at lumbar spine (L1-L4) in moderate OSA patients was higher than control and severe OSA group significantly (p = 0.036). After adjustment for confounding factors, stepwise multiple linear regression analyses showed LaSO2 (β = 0.340, p = 0.008) as an independent explanatory variable for Lumbar L1–L4 BMD, LaSO2 (β = 0.304, p = 0.037), BMI (β = 0.393, p = 0.008) for femur neck BMD and BMI (β = 0.720, p = 0.002) for hip total BMD. Conclusions.Our finding indicated that there was a relationship between OSA and bone metabolism in younger men, and moderate OSA-related hypoxia positively related with BMD. This study also showed that different degrees of recurrent hypoxia had different effects on bone metabolism, a finding that required further investigation.

Matrix metalloproteinase-9 and substance-P as predictors for early-stage diagnosis of acute mountain sickness

IntroductionAlthough acute mountain sickness (AMS) can be a life-threatening condition, early diagnosis is difficult due to vague and non-specific symptoms. The aim of this study is to investigate biochemical markers that can detect high-altitude diseases in advance. Eight different biomarkers (BNP, HIF-1α, NGAL, MMP-3, MMP-9, SESN2, substance P (SP), and U-II) were studied, and their relationship with AMS was investigated. MethodsOf the 84 mountaineers who participated in the mountaineering training organized by the Turkish Mountaineering Federation in the Rize Kaçkar Mountains in 2018, 52 volunteered to participate in the study. Twelve hours after the participants reached an altitude of 2200 m (exposed to moderate hypoxia), their vital parameters were measured, and blood samples were taken for biochemistry tests. Vital signs and Lake Louise (LL) AMS scores were recorded every 24 h during the following 72 h. The participants were divided into two groups according to their LL scores: those with AMS and those without (AMS+ and AMS −), and the vital parameters and biomarker levels of both groups were compared and evaluated. ResultsOf the volunteers participating in the study, 35 (67.3%) were male and 17 (32.7%) were female, although there was no gender difference in terms of susceptibility to AMS. Among the investigated markers in the AMS + group, MMP-9 and SP were statistically significantly higher (p = 0.037 and p = 0.038, respectively). There were no statistical differences between AMS− and AMS+ groups with regard to heart rate, oxygen saturation, and systolic and diastolic blood pressure values (p = 0.507, p = 0.929, p = 0.955, p = 0.572, respectively). ConclusionThere were significant differences between the AMS− and AMS+ groups in terms of MMP-9 and SP. However, differences in physical indexes between the groups were not statistically significant. This could provide objective indexes for scanning and screening individuals susceptible to AMS in the early stages of rapid ascending.

PATHOPHYSIOLOGY OF MOLECULAR HYDROGEN INFLUENCE ON ACUTE KIDNEY DAMAGE IN HEMIC HYPOXIA

When hemoglobin is inactivated by nitrites, hypoxia of the renal tubules is not accompaniedby inhibition of renal blood circulation. At the same time, the fi ltration fraction of sodiumions and the load on the energy- dependent mechanisms of the proximal and distal tubules remain high, but since there is no energy, signifi cant reactions of damage to the proximalnephron and dysfunction of the distal tubules as reabsorption of sodium than in theproximal tubule are observed. To correct the detected disorders, it is advisable to usean antioxidant solution of negative redox potential with hydrogen saturation, whichcan penetrate into cells, reach mitochondria, penetrate areas of ischemia, edema andinfl ammation, improve energy supply by means of supplying additional electrons anddetecting neutralization of hydroxyl radical and peroxynitrite.Purpose – to determine the eff ect of an antioxidant solution of negative redox potentialwith molecular hydrogen saturation on the functional and biochemical processes of thekidneys in acute hemic hypoxia of moderate severity.Materials and methods. The experiments were performed on 30 white nonlinear malerats weighing 0.16-0.18 kg under the conditions of hyposodium diet. Simulation ofexperimental hemic hypoxia was performed by a single subcutaneous injection of 1%sodium nitrite solution at a dose of 50 mg / kg body weight, causing, respectively, theaverage severity of hemic hypoxia. An antioxidant solution of negative redox potentialwith hydrogen saturation 1.0-1.2 ppm and redox potential –297.3 ± 5.27 mV was obtainedusing a new generation generator Blue Water 900 (Korea). Experimental, physiological,biochemical, immunoenzyme, histoenzymo- chemical and statistical research methodswere used.Results. The development of acute hemic hypoxia of moderate severity was accompaniedby an increase in glomerular fi ltration, protein excretion, decreased distal reabsorptionof sodium ions. An increase in the concentration of tumor necrosis factor- alpha in bloodplasma was found and an increase in unlimited proteolysis in the kidneys was detected:by azocollagen lysis in the cortex, azocasein in the medullary substance and azoalbuminin the papilla. Moderate hemic hypoxia showed an increase in the concentration of lipidperoxidation products: malonic aldehyde and diene conjugates in the renal medulla andinhibition of succinate dehydrogenase activity in the proximal nephron (p &lt;0.01). Theuse of a solution of negative redox potential with molecular hydrogen saturation hada corrective eff ect on the studied parameters.Conclusions. 1. In acute hemic hypoxia of moderate severity, a solution of negative redoxpotential with molecular hydrogen saturation due to its antioxidant, cytoprotective, energyproperties improves the condition of the proximal tubule, reduces the manifestations ofproteinuria (p &lt;0,01), increases tubular type succinate dehydrogenase activity (p &lt;0.02)in this part of the nephron. 2. The use of a solution of negative redox potential withmolecular hydrogen saturation due to its antioxidant, anti-infl ammatory, nephroprotectiveproperties has a protective eff ect on the kidneys and reduces elevated levels of tumornecrosis factor- alpha in blood plasma (p &lt;0,01), lysis azocollagen, azoalbumin, azocaseinand lipid peroxidation products of malonic aldehyde (p &lt;0.01) and diene conjugates inacute hemic hypoxia of moderate severity.

Effect of Hypoxia-Induced Micro-RNAs Expression on Oncogenesis.

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. An aberrant regulation of gene expression by miRNAs is associated with numerous diseases, including cancer. MiRNAs expression can be influenced by various stimuli, among which hypoxia; however, the effects of different types of continuous hypoxia (moderate or marked) on miRNAs are still poorly studied. Lately, some hypoxia-inducible miRNAs (HRMs, hypoxia-regulated miRNAs) have been identified. These HRMs are often activated in different types of cancers, suggesting their role in tumorigenesis. The aim of this study was to evaluate changes in miRNAs expression both in moderate continuous hypoxia and marked continuous hypoxia to better understand the possible relationship between hypoxia, miRNAs, and colorectal cancer. We used RT-PCR to detect the miRNAs expression in colorectal cancer cell lines in conditions of moderate and marked continuous hypoxia. The expression of miRNAs was analyzed using a two-way ANOVA test to compare the differential expression of miRNAs among groups. The levels of almost all analyzed miRNAs (miR-21, miR-23b, miR-26a, miR-27b, and miR-145) were greater in moderate hypoxia versus marked hypoxia, except for miR-23b and miR-21. This study identified a series of miRNAs involved in the response to different types of continuous hypoxia (moderate and marked), highlighting that they play a role in the development of cancer. To date, there are no other studies that demonstrate how these two types of continuous hypoxia could be able to activate different molecular pathways that lead to a different expression of specific miRNAs involved in tumorigenesis.

Sprint Interval Exercise Improves Cognitive Performance Unrelated to Postprandial Glucose Fluctuations at Different Levels of Normobaric Hypoxia.

Objective: The aim of our study was to examine cognition response to sprint interval exercise (SIE) against different levels of hypoxia. Research design and methods: 26 recreational active males performed SIE (20 × 6 s of all-out cycling bouts, 15 s of passive recovery) under normoxia (FIO2: 0.209), moderate hypoxia (FIO2: 0.154), and severe hypoxia (FIO2: 0.112) in a single-blinded crossover design. Cognitive function and blood glucose were assessed before and after 0, 10, 30, and 60 min of the SIE. Heart rate (HR), peripheral oxygen saturation (SpO2), and ratings of perceived exertion (RPE, the Borg 6–20-point scale) during each SIE trial were recorded before and immediately after every five cycling bouts, and after 0, 10, 30, and 60 min of the SIE. Results: All the three SIE trials had a significantly faster overall reaction time in the Stroop test at 10 min after exercise as compared to that of the baseline value (p = 0.003, ƞ2 = 0.606), and returned to normal after 60 min. The congruent RT at 10 min after SIE was significantly shorter than that of the baseline (p < 0.05, ƞ2 = 0.633), while the incongruent RT at both 10 min and 30 min were significantly shorter than that measured at baseline (p < 0.05, ƞ2 = 0.633). No significant differences in terms of accuracy were found across the three trials at any time points (p = 0.446, ƞ2 = 0.415). Blood glucose was significantly reduced at 10 min and was sustained for at least 60 min after SIE when compared to pre-exercise in all trials (p < 0.05). Conclusions: Acute SIE improved cognitive function regardless of oxygen conditions, and the sustained improvement following SIE could last for at least 10–30 min and was unaffected by the altered blood glucose level.

Depletion of HIF-1α by Inducible Cre/loxP Increases the Sensitivity of Cultured Murine Hepatocytes to Ionizing Radiation in Hypoxia.

The transcription factor hypoxia-inducible factor (HIF) is the main oxygen sensor which regulates adaptation to cellular hypoxia. The aim of this study was to establish cultured murine hepatocyte derived cells (mHDC) as an in vitro model and to analyze the role of HIF-1α in apoptosis induction, DNA damage repair and sensitivity to ionizing radiation (IR). We have crossed C57/BL6 mice that bear loxP sites flanking exon 2 of Hif1a with mice which carry tamoxifen-inducible global Cre expression. From the offspring, we have established transduced hepatocyte cultures which are permanently HIF-1α deficient after tamoxifen treatment. We demonstrated that the cells produce albumin, acetylcholine esterase, and the cytokeratins 8 and 18 which functionally characterizes them as hepatocytes. In moderate hypoxia, HIF-1α deficiency increased IR-induced apoptosis and significantly reduced the surviving fraction of mHDC as compared to HIF-1α expressing cells in colony formation assays. Furthermore, HIF-1α knockout cells displayed increased IR-induced DNA damage as demonstrated by increased generation and persistence of γH2AX foci. HIF-1α deficient cells showed delayed DNA repair after IR in hypoxia in neutral comet assays which may indicate that non-homologous end joining (NHEJ) repair capacity was affected. Overall, our data suggest that HIF-1α inactivation increases radiation sensitivity of mHDC cells.

Acute physiological response to a normobaric hypoxic exposure: sex differences.

Although preliminary studies suggested sex-related differences in physiological responses to altitude/hypoxia, controlled studies from standardised exposures to normobaric hypoxia are largely lacking. Hence, the goals of this study were to provide information on cardiorespiratory responses to a 7-h normobaric hypoxia exposure and to explore potential differences between men and women. In this crossover study, a total of 15 men and 14 women were subjected to a 7-h exposure in normoxia (FiO2: 21%) and normobaric hypoxia (FiO2: 15%). Values of peripheral oxygen saturation, heart rate, systolic and diastolic blood pressure and respiratory gases were recorded every hour (8 time points), and oxygen saturation every 30min (15 time points). Compared to normoxia, exposure to hypoxia significantly increased minute ventilation from baseline to hour 7 in males (+ 71%) and females (+ 40%), significantly greater in men (p < 0.05). A steeper decrease in peripheral oxygen saturation until 2.5h in hypoxia was seen in females compared to males (p < 0.05). In conclusion, the ventilatory response to hypoxia was more pronounced in men compared to women. Moreover, during the first hours in hypoxia, peripheral oxygen saturation dropped more markedly in women than in men, likely due an initially lower and/or less efficient ventilatory response to moderate hypoxia. Those findings should be considered when performing interventions for therapy or prevention in normobaric hypoxia. Nevertheless, further large-scaled and well-controlled studies are needed.

Interplay of temperature and hypoxia in habitat quality for a juvenile demersal fish in a coastal upwelling system

Coastal hypoxia around the world has raised concerns about its sublethal effects on juvenile demersal fishes. We examined the growth rate of juvenile English sole ( Parophrys vetulus) under 15 combinations of temperature and dissolved oxygen levels. We found interactive effects of temperature and hypoxia on fish growth. Fish exposed to moderate hypoxia and normoxia exhibited similar growth responses to increasing temperature; however, a threshold effect was evident under severe hypoxia, which caused a significant reduction in growth. Further, a generalized additive mixed model was applied to simulate fish growth off the Oregon coast during a climate transition from the 2009 El Niño to the 2010–2011 La Niña. Model simulations indicated that habitat quality varied significantly between estuarine (high quality) and coastal (low quality) nurseries. Coastal habitats may remain moderately suitable during El Niño years, while estuarine refuges are more preferred during La Niña years. This study contributes to the assessment of climate change and hypoxic disturbance on demersal fisheries by providing an analytical framework to evaluate synergistic temperature–hypoxia interactions on juveniles in their nursery habitats.

Profound hypercapnia but only moderate hypoxia found during underwater rugby play

Background: Underwater rugby is a team sport where players try to score points with a negatively buoyant ball while submerged in a swimming pool. Reports of syncope incidents at the Swedish Championships led to us to investigate end-tidal oxygen and carbon dioxide levels during simulated match play. Methods: Eight male underwater rugby club players of varying experience participated. Repetitive measurements were made while players were defending during simulated match play. Each time a player surfaced they exhaled through a mouthpiece connected to a flow meter and a gas analyzer to measure tidal volume, PETO2 and PETCO2. Results: Measurements were made over 12 dives, with an average dive duration of 18.5 seconds. The mean maximal PETCO2 across the eight participants was 10.0 kPa (~75 mmHg) (range, 9.1–11.7 [~68–88]). The corresponding mean minimum PETO2 was 7.6 kPa (~57 mmHg) (6.3–10.4 [~47–78)). PETCO2 drifted upward, with the mean upward change from the first to last dive for each participant being +1.8 (~13.5 mmHg) (SD 1.74) kPa. A similar trend for PETO2 was not detected, with a mean change of -0.1 (~0.75 mmHg) (SD 3.79) kPa. Conclusion: Despite high PETCO2 values that were close to narcotic being recorded, these players seemed to regulate their urge to breathe based on hypoxia rather than hypercapnia.