Acute Hypoxic Exposure Research Articles

Changes in cycling economy and fractional utilization of V̇O2peak during a 40-min maximal effort exercise test with acute hypobaric hypoxia corresponding to 2800 m of altitude.

Peak oxygen uptake (V̇O2peak ) declines by ~7% per 1000 m of increasing altitude, whereas exercise performance seems reduced to a lesser extent. For example, 800-10 000 m track and field performances are decreased by 0.4%-2.4% above 1000 m as compared to below and some studies show similar drops in cycling performance. A greater decline in V̇O2peak than in endurance performance with altitude suggests a higher fractional utilization of V̇O2peak (%V̇O2peak ). Therefore, we hypothesized that the %V̇O2peak is higher with acute hypoxic exposure than near sea level. Sixteen lowlanders (8 women, age: 31 ± 7 years [mean ± SD], body mass: 68 ± 8 kg, V̇O2peak : 60 ± 8 mL min-1 kg-1 ) underwent cycling testing in a hypobaric hypoxic chamber on 6 test days, three conducted at 300 m and three at 2800 m of acute altitude. At both altitudes, V̇O2peak was determined, and during a 40-min all out maximal effort time trial (TT), mean power output (MPO) and mean V̇O2 (%V̇O2peak ) were assessed. V̇O2peak decreased by 11.2 ± 3.0% (p < 0.001), while MPO during the TT declined by 10.7 ± 3.1% (p < 0.001) at 2800 m as compared to 300 m. During the TT, %V̇O2peak was higher at altitude, corresponding to 75.9 ± 4.5% at 300 m and 78.8 ± 4.2% at 2800 m (p = 0.011), and cycling economy (mL O2 kJ-1 ) was poorer (+3.4 ± 2.7%, p < 0.001). The %V̇O2peak was higher during a cycling TT at 2800 m of altitude than near sea level, while cycling economy was poorer. This resulted in a similar reduction in performance and V̇O2peak . Future studies should address the physiological mechanisms underlying the elevated %V̇O2peak .

DIA-based serum proteomics revealed the protective effect of modified siwu decoction against hypobaric hypoxia

Ethnopharmacological relevanceSiwu decoction (SWD) is a common traditional formula for nourishing blood, and its derived formulas are also widely used in traditional Chinese medicine (TCM) clinic. However, the protective effects of SWD and its derived formulas on blood deficiency and blood stasis caused by rushing to the plateau are rarely reported, and the underlying mechanism has not been fully elucidated. Aim of the studyThis study explores the pharmacological effects and mechanisms of modified siwu decoction (MSWD) adding Persicae Semans (Prunus persica (L.) Batsch) and Carthami Flos (Carthamus tinctorius L.) against hypobaric hypoxia (HH). The acute toxicity of MSWD was also evaluated to further validate the potential of MSWD as a therapeutic candidate for HH. Materials and methodsHypoxic models of C57BL/6 J and KM male mice were used to evaluate the pharmacological effect of MSWD. 2 μL serum sample of C57BL/6 J mice was digested into peptide mixtures and analyzed with DIA mode on an Orbitrap Fusion Lumos mass spectrometer after LC separation. The peptide and protein identifications were limited to a 1% FDR. Screening of differential expressed proteins, correlation analysis, hierarchical clustering analysis, principal components analysis and Mfuzz analysis were all performed by R packages. The protein−protein interaction network was analyzed using the STRING website and constructed with Cytoscape software. ResultsMSWD showed a protective effect against acute hypoxia exposure through increasing the number of red blood cells and improving hemodynamics indexes in mice. Meanwhile, the biochemical results showed that MSWD could reduce the inflammation and oxidative stress, reduce the content of organ injury biomarkers and significantly improve the high-intensity exercise ability of mice. Subsequently, serum DIA proteomic results revealed significant changes in proteomic characteristics after MSWD intervention. Specifically, proteins related to oxidative stress and ubiquitin-proteasome system, such as Sod1, Gstp1, Vcp and Usp14, were down-regulated after MSWD intervention, suggesting that the protective effect of MSWD involved the reduction of oxidative stress and energy expenditure. MSWD also intervened in energy metabolism and lipid metabolism processes by altering the expression levels of Eno1, Sphk1 and Apoa1 to ameliorate hypoxia-induced disorders. At the same time, MSWD acute toxicity test showed no obvious toxicity. ConclusionsMSWD has a good protective effect against HH by ameliorating hypoxia-induced disorders of energy and lipid metabolism, supporting MSWD as a safe drug candidate for the prevention and treatment of acute hypoxia fatigue.

A Single 10-Minute E-cigarette Vapor Exposure Reduces Tidal Volume and Minute Ventilation in Normoxia and Normobaric Hypoxia in Adult Rats.

The present study investigated the effects of a single 10-minute exposure to e-cigarette vapor on ventilation in adult male Long-Evans rats. Ventilation was recorded using awake, unrestrained whole-body plethysmography. Baseline recordings were taken the day before full-body exposure to either room air (n = 9; air control group) or e-cigarette vapor (n = 9; treatment group). Post-exposure recordings were taken immediately after the 10-minute room air or vapor exposure. As part of the ventilation protocol, in addition to recording the subject's ventilation in room air, the subjects were also exposed to 10% oxygen (balanced with nitrogen) to assess the effects of e-cigarette vapor on an increased drive to breathe. Ventilation data were analyzed using a 2x2x2 mixed-model ANOVA measuring treatment (vape vs. air) x time (baseline vs. post-treatment) x condition (normoxia vs. hypoxia) for breathing frequency, tidal volume, and minute ventilation. Breathing frequency increased in both treatment groups (air and vape) with exposure to normobaric hypoxia (p < 0.001), with no effect of time (baseline vs. post-treatment) for either group. Tidal volume increased in both treatment groups (air and vape) with exposure to normobaric hypoxia (p < 0.001), and an effect of time (baseline vs. post-treatment) was observed (p = 0.010) for the vape group. Minute ventilation increased in both treatment groups (air and vape) with exposure to normobaric hypoxia (p < 0.001), and an effect of time (baseline vs. post-treatment) was observed (p < 0.001) for the vape group. In conclusion, immediately following a single 10-minute e-cigarette vapor exposure, both tidal volume and minute ventilation were reduced during normoxia and normobaric hypoxia, indicating a decrease in ventilation after a single 10-minute e-cigarette vapor exposure. Furthermore, this exposure also blunted the physiological response to acute hypoxia exposure. Subjects in the vape group, while breathing more rapidly as expected, experienced shallower breathing than the air group during hypoxia. The findings in this study confirm that vaping could result in reduced lung function.

Effects of Hypoxemia by Acute High-Altitude Exposure on Human Intestinal Flora and Metabolism.

This study examined the effects of hypoxemia caused by acute high-altitude hypoxia (AHAH) exposure on the human intestinal flora and its metabolites. The changes in the intestinal flora, metabolism, and erythropoietin content in the AHAH population under altitude hypoxia conditions were comprehensively analyzed using 16S rRNA sequencing, metabonomics, and erythropoietin content. The results showed that compared with those in the control group (C group), the flora and metabolites in the hypoxemia group (D group) were altered. We found alterations in the flora according to the metabolic marker tyrosine through random forest and ROC analyses. Fecal and serum metabonomics analyses revealed that microbial metabolites could be absorbed into the blood and participate in human metabolism. Finally, a significant correlation between tyrosine and erythropoietin (EPO) content was found, which shows that human intestinal flora and its metabolites can help to confront altitude stress by regulating EPO levels. Our findings provide new insights into the adaptive mechanism and prevention of AHAH.

The Effects Of Acute Hypoxia Exposure On Cognitive Function

The Effects Of Acute Hypoxia Exposure On Cognitive Function

A randomized controlled crossover trial of acute intermittent and continuous hypoxia exposure in mild-moderate obstructive sleep apnea: A feasibility study.

In a prospective, randomized, controlled crossover study, we explored the effects of acute intermittent hypoxia and acute continuous hypoxia on patients with mild-moderate obstructive sleep apnea. Over three single-night sessions, subjects were alternately exposed to normoxia, acute continuous hypoxia and acute intermittent hypoxia before sleep. The apnea-hypopnea index and oxygen desaturation index were used to diagnose obstructive sleep apnea and evaluate efficacy. A responder was defined as a participant with a ≥ 50% reduction in apnea-hypopnea index between normoxia and hypoxia exposure. Sixteen participants with mild-moderate obstructive sleep apnea completed the study. Compared with normoxia, the mean apnea-hypopnea index decreased by 8.9 events per hr (95% confidence interval, 4.2-13.6, p = 0.001) with acute intermittent hypoxia and by 4.1 events per hr (95% confidence interval, 0.5-8.8, p = 0.082) with acute continuous hypoxia, equating to a mean decrease in apnea-hypopnea index of 4.8 events per hr (95% confidence interval, 0.1-9.5, p = 0.046) with acute intermittent hypoxia compared with acute continuous hypoxia. Compared with normoxia, the mean oxygen desaturation index decreased by 9.8 events per hr (95% confidence interval, 4.4-15.1, p = 0.001) with acute intermittent hypoxia but did not significantly decrease with acute continuous hypoxia; the mean oxygen desaturation index decreased by 7.2 events per hr (95% confidence interval, 1.8-12.6, p = 0.010) with acute intermittent hypoxia compared with acute continuous hypoxia. Of the 16 participants, 11 responded to acute intermittent hypoxia and four responded to acute continuous hypoxia (p = 0.032), of whom eight of 11 cases and all four cases had oxygen desaturation indexes <5 events per hr, respectively (p = 0.273). All participants tolerated acute intermittent hypoxia and there were no obvious adverse events during acute intermittent hypoxia exposure. In conclusion, acute intermittent hypoxia exposure improved apnea-hypopnea index and oxygen desaturation index in patients with mild-moderate obstructive sleep apnea, suggesting that further prospective validation of intermittent hypoxia exposure in patients with obstructive sleep apnea is needed to establish its clinical feasibility as a therapeutic modality.

The severity of acute hypoxaemia determines distinct changes in intracortical and spinal neural circuits.

The purpose of this study was to examine how two common methods of continuous hypoxaemia impact the activity of intracortical circuits responsible for inhibition and facilitation of motor output, and spinal excitability. Ten participants were exposed to 2h of hypoxaemia at 0.13 fraction of inspired oxygen ( clamping protocol) and 80% of peripheral capillary oxygen saturation ( clamping protocol) using a simulating altitude device on two visits separated by a week. Using transcranial magnetic and peripheral nerve stimulation, unconditioned motor evoked potential (MEP) area, short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), and F-wave persistence and area were assessed in the first dorsal interosseous (FDI) muscle before titration, after 1 and 2h of hypoxic exposure, and at reoxygenation. The clamping protocols resulted in differing reductions in by 2h ( clamping protocol: 81.9±1.3%, clamping protocol: 90.6±2.5%). Although unconditioned MEP peak to peak amplitude and area did not differ between the protocols, SICI during clamping was significantly lower at 2h compared to clamping (P=0.011) and baseline (P<0.001), whereas ICF was higher throughout the clamping compared to clamping (P=0.005). Furthermore, a negative correlation between SICI and (rrm =-0.56, P=0.002) and a positive correlation between ICF and (rrm =0.69, P=0.001) were determined, where greater reductions in correlated with less inhibition and less facilitation of MEP responses. Although F-wave area progressively increased similarly throughout the protocols (P=0.037), persistence of responses was reduced at 2h and reoxygenation (P<0.01) during the clamping protocol compared to the clamping protocol. After 2h of hypoxic exposure, there is a reduction in the activity of intracortical circuits responsible for inhibiting motor output, as well as excitability of spinal motoneurones. However, these effects can be influenced by other physiological responses to hypoxia (i.e., hyperventilation and hypocapnia). NEW FINDINGS: What is the central question of this study? How do two common methods of acute hypoxic exposure influence the excitability of intracortical networks and spinal circuits responsible for motor output? What is the main finding and its importance? The excitability of spinal circuits and intracortical networks responsible for inhibition of motor output was reduced during severe acute exposure to hypoxia at 2 h, but this was not seen during less severe exposure. This provides insight into the potential cause of variance seen in motor evoked potential responses to transcranial magnetic stimulation (corticospinal excitability measures) when exposed to hypoxia.

Gamified assessment of cognitive performance during moderate hypoxia.

There is a need for rapid and objective assessment tools to identify people at risk of impaired cognitive function during hypoxia. To test the hypotheses that performance on gamified cognitive tests examining the cognitive domains of executive function (Gridshot), working memory (Capacity) and spatial tracking (Multitracker) will be reduced during normobaric exposure to moderate normobaric hypoxia. Following three consecutive days of practice, twenty-one healthy adults (27 ± 5 y, 9 females) completed five 1-min rounds of the tablet-based games Gridshot, Capacity, and Multitracker (Statespace Labs, Inc.) at Baseline and 60 and 90 min after exposure to 14.0 ± 0.2% (hypoxia) and 20.6 ± 0.3% (normoxia) oxygen. Both conditions were completed on the same day and were administered in a single-blind, block randomized manner. Arterial oxyhemoglobin saturation was estimated via forehead pulse oximetry (SpO2). Data were analyzed using ANCOVA with a covariate of Baseline. Compared to normoxia (98 ± 1%), SpO2 was lower (p < 0.001) at 60 (91 ± 3%) and 90 (91 ± 2%) min of hypoxia. No condition x time interaction effects were identified for any gamified cognitive tests (p ≥ 0.32). A main effect of condition was identified for Capacity (p = 0.05) and Multitracker (p = 0.04), but not Gridshot (p = 0.33). Post hoc analyses of the composite scores for both Capacity (p = 0.11) and Multitracker (p = 0.73) demonstrated no difference between conditions. Performance on gamified cognitive tests was not consistently affected by acute normobaric moderate hypoxic exposure.

Characterisation of the acute hypoxic response using breathing variability parameters: A pilot study in humans

PurposeWe aimed to investigate respiratory rate variability (RRV) and tidal volume (Vt) variability during exposure to normobaric hypoxia (i.e., reduction in the fraction of inspired oxygen - FiO2), and the association of the changes in RRV and Vt variability with the changes in pulse oxygen saturation (SpO2). MethodsThirty healthy human participants (15 females) were exposed to: (1) 15-min normoxia, (2) 10-min hypoxia simulating 2200 m, (3) 10-min hypoxia simulating 4000 m, (4) 10-min hypoxia simulating 5000 m, (5) 15-min recovery in normoxia. Linear regression modelling was applied with SpO2 (dependent variable) and the changes in RRV and Vt variability (independent variables), controlling for FiO2, age, sex, changes in heart rate (HR), changes in HR variability (HRV), and changes in minute ventilation (VE). ResultsWhen modelling breathing parameter variability as root-mean-square standard deviation (RMSSD), a significant independent association of the changes in RRV with the changes in SpO2 was found (B = −4.3e-04, 95% CI = −8.3e-04/−2.1e-05, p = 0.04). The changes in Vt variability showed no significant association with the changes in SpO2 (B = −1.6, 95% CI = −5.5/2.4, p = 0.42). When modelling parameters variability as SD, a significant independent association of the changes in RRV with the changes in SpO2 was found (B = −8.2e-04, 95% CI = −1.5e-03/−9.4e-05, p = 0.03). The changes in Vt variability showed no significant association with the changes in SpO2 (B=1.4, 95% CI = −5.8/8.6, p = 0.69). ConclusionHigher RRV is independently associated with lower SpO2 during acute hypoxic exposure, while Vt variability parameters are not. Therefore, RRV may be a potentially interesting parameter to characterize individual responses to acute hypoxia.

The change of attention network functions and physiological adaptation during high-altitude hypoxia and reoxygenation

Previous studies have not reached a definitive conclusion regarding the effect of high-altitude hypoxia and reoxygenation on attention. To clarify the influence of altitude and exposure time on attention and the relations between physiological activity and attention, we conducted a longitudinal study to track attention network functions in 26 college students. The scores on the attention network test and physiological data, including heart rate, percutaneous arterial oxygen saturation (SpO2), blood pressure, and vital capacity in pulmonary function measurement, were collected at five time-points: two weeks before arriving at high altitude (baseline), within 3 days after arriving at high altitude (HA3), 21 days after arriving at high altitude (HA21), 7 days after returning to sea level (POST7) and 30 days after returning to sea level (POST30). The alerting scores at POST30 were significantly higher than those at baseline, HA3 and HA21; the orienting scores at HA3 were lower than those at POST7 and POST30; the executive control scores at POST7 were significantly lower than those at baseline, HA3, HA21, and POST30; and the executive control scores at HA3 were significantly higher than those at POST30. The change in SpO2 during high-altitude acclimatization (from HA3 to HA21) was positively correlated with the orienting score at HA21. Vital capacity changes during acute deacclimatization positively correlated with orienting scores at POST7. Attention network functions at the behavioral level did not decline after acute hypoxia exposure compared with baseline. Attention network functions after returning to sea level were improved compared with those during acute hypoxia; additionally, alerting and executive function scores were improved compared with those at baseline. Thus, the speed of physiological adaptation could facilitate the recovery of orienting function during acclimatization and deacclimatization.

Remote ischemic preconditioning improves spatial memory and sleep of young males during acute high-altitude exposure

ObjectiveThe high-altitude hypoxia environment will cause poor acclimatization in a portion of the population. Remote ischemic preconditioning（RIPC）has been demonstrated to prevent cardiovascular and cerebrovascular diseases under ischemic or hypoxic conditions. However, its role in improving acclimatization and preventing acute mountain sickness (AMS) at high altitude has been undetermined. This study aims to estimate the effect of RIPC on acclimatization of individuals exposed to high altitude. MethodsThe project was designed as a randomized controlled trial with 82 healthy young males, who received RIPC training once a day for 7 consecutive days. Then they were transported by aircraft to a high altitude (3680 m) and examined for 6 days. Lake Louise Score(LLS) of AMS, physiological index, self-reported sleep pattern, and Pittsburgh Sleep Quality Index（PSQI）score were applied to assess the acclimatization to the high altitude. Five neurobehavioral tests were conducted to assess cognitive function. ResultsThe result showed that the RIPC group had a significantly lower AMSscore than the control group (2.43 ± 1.58 vs 3.29 ± 2.03, respectively; adjusted mean difference-0.84, 95% confidence interval-1.61 to −0.06, P = 0.036). and there was no significant difference in AMS incidence between the two groups (25.0% vs 28.57%, P = 0.555). The RIPC group performed better than the control group in spatial memory span score (11[9-12] vs 10[7.5-11], P=0.025) and the passing digit (7[6-7.5] vs 6[5-7], P= 0.001). Spatial memory was significantly higher in the high-altitude RIPC group than in the low-altitude RIPC group (P＜0.01). And the RIPC group obtained significantly lower self-reported sleep quality score (P = 0.024) and PSQI score (P = 0.031). ConclusionsThe RIPC treatment improved spatial memory and sleep quality in subjects exposed to acute hypoxic exposure and this may lead to improved performance at high altitude.

Combining hypoxia with thermal stimuli in humans: physiological responses and potential sex differences.

Increasing prevalence of native lowlanders sojourning to high altitudes (>2,500 m) for recreational, occupational, military, and competitive reasons has generated increased interest in physiological responses to multistressor environments. Exposure to hypoxia poses recognized physiological challenges that are amplified during exercise and further complicated by environments that might include combinations of heat, cold, and high altitude. There is a sparsity of data examining integrated responses in varied combinations of environmental conditions, with even less known about potential sex differences. How this translates into performance, occupational, and health outcomes requires further investigation. Acute hypoxic exposure decreases arterial oxygen saturation, resulting in a reflex hypoxic ventilatory response and sympathoexcitation causing an increase in heart rate, myocardial contractility, and arterial blood pressure, to compensate for the decreased arterial oxygen saturation. Acute altitude exposure impairs exercise performance, for example, reduced time to exhaustion and slower time trials, largely owing to impairments in pulmonary gas exchange and peripheral delivery resulting in reduced V̇o2max. This exacerbates with increasing altitude, as does the risk of developing acute mountain sickness and more serious altitude-related illnesses, but modulation of those risks with additional stressors is unclear. This review aims to summarize and evaluate current literature regarding cardiovascular, autonomic, and thermoregulatory responses to acute hypoxia, and how these may be affected by simultaneous thermal environmental challenges. There is minimal available information regarding sex as a biological variable in integrative responses to hypoxia or multistressor environments; we highlight these areas as current knowledge gaps and the need for future research.

Alteration of antioxidant status, glucose metabolism, and hypoxia signal pathway in Eirocheir sinensis after acute hypoxic stress and reoxygenation

Dissolved oxygen (DO) is crucial for the survival of Chinese mitten crab (Eirocheir sinensis); low DO levels adversely affect the health of these crabs. In this study, we evaluated the underlying response mechanism of E. sinensis to acute hypoxic stress by analyzing antioxidant parameters, glycolytic indicators, and hypoxia signaling factors. The crabs were exposed to hypoxia for 0, 3, 6, 12, and 24 h and reoxygenated for 1, 3, 6, 12, and 24 h. The hepatopancreas, muscle, gill, and hemolymph were sampled at different exposure times to detect the biochemical parameters and gene expression. The results showed that the activity of catalase, antioxidants, and malondialdehyde in tissues significantly increased under acute hypoxia and gradually decreased during the reoxygenation phase. Under acute hypoxic stress, glycolysis indices, including hexokinase (HK), phosphofructokinase, pyruvate kinase (PK), pyruvic acid (PA), lactate dehydrogenase (LDH), lactic acid (LA), succinate dehydrogenase (SDH), glucose, and glycogen in the hepatopancreas, hemolymph, and gills increased to varying degrees but recovered to the control levels after reoxygenation. Gene expression data showed that hypoxia signaling pathway-related genes, including hypoxia-inducible factor-1α/β (HIF1α/β), prolyl hydroxylase (PHD), factor inhibiting hypoxia-inducible factor (FIH), and glycolysis-related factors (HK and PK) were upregulated, showing that the HIF signaling pathway was activated under hypoxic conditions. In conclusion, acute hypoxic exposure activated the antioxidant defense system, glycolysis, and HIF pathway to respond to adverse conditions. These data contribute to elucidating the defense and adaptive mechanisms of crustaceans to acute hypoxic stress and reoxygenation.

Time-course effects and mechanisms of hypobaric hypoxia on nervous system in mice

ObjectiveThe aim of this study was to investigate the effect of time course on neurological impairment after acute hypobaric hypoxia exposure in mice and clarify the mechanism of acclimatization, so as to provide a suitable mice model and identify potential target against hypobaric hypoxia for further drug research. MethodMale C57BL/6J mice were exposed to hypobaric hypoxia at a simulated altitude of 7000 m for 1, 3, and 7 days (1HH, 3HH and 7HH respectively). The behavior of the mice was evaluated by novel object recognition (NOR) and morris water maze test (MWM), then, the pathological changes of mice brain tissues were observed by H&E and Nissl staining. In addition, RNA sequencing (RNA-Seq) was performed to characterize the transcriptome signatures, and enzyme-linked immunosorbent assay (ELISA), Real-time polymerase chain reaction (RT-PCR), and western blot (WB) were used to verify the mechanisms of neurological impairment induced by hypobaric hypoxia. ResultThe hypobaric hypoxia condition resulted in impaired learning and memory, decreased new object cognitive index, and increased escape latency to the hidden platform in mice, with significant changes seen in the 1HH and 3HH groups. Bioinformatic analysis of RNA-seq results of hippocampal tissue showed that 739 differentially expressed genes (DEGs) appeared in the 1HH group, 452 in the 3HH group, and 183 in the 7HH group compared to the control group. There were 60 key genes overlapping in three groups which represented persistent changes and closely related biological functions and regulatory mechanisms in hypobaric hypoxia-induced brain injuries. DEGs enrichment analysis showed that hypobaric hypoxia-induced brain injuries were associated with oxidative stress, inflammatory responses, and synaptic plasticity. ELISA and WB results confirmed that these responses occurred in all hypobaric hypoxic groups while attenuated in the 7HH group. VEGF-A-Notch signaling pathway was enriched by DEGs in hypobaric hypoxia groups and was validated by RT-PCR and WB. ConclusionThe nervous system of mice exposed to hypobaric hypoxia exhibited stress followed by gradual habituation and thus acclimatization over time, which was reflected in the biological mechanism involving inflammation, oxidative stress, and synaptic plasticity, and accompanied by activation of the VEGF-A-Notch pathway.

Physiological responses to acute hypoxia in the liver of largemouth bass by alteration of mitochondrial function and Ca2+ exchange

Oxygen is a critical factor for most organisms and this is especially true for aquatic animals. Unfortunately, high-density aquaculture farming practices and environmental degradation will inevitably lead to hypoxic stress in fishes such as largemouth bass (Micropterus salmoides). Thus, characterizing the physiological responses during acute hypoxia exposure is extremely important for understanding the adaptation mechanisms of largemouth bass to hypoxia. The present study aimed to investigate mitochondrial function and Ca2+ exchange in largemouth bass under hypoxic conditions. Largemouth bass were subjected to hypoxia (1.2 ± 0.2 mg/L) for 24 h Liver mitochondria and endoplasmic reticulum (ER) parameters were analyzed. We used Liquid chromatography-mass spectrometry (LC-MS) to further elucidate the pattern of energy metabolism. Changes of Ca2+ concentrations were observed in primary hepatocytes of largemouth bass under hypoxic conditions. Our results indicate that the morphology and function of the mitochondria and ER were altered under hypoxia. First, the occurrence of autophagy was accompanied by reactive oxygen species (ROS) generation and electron transport chain (ETC) activity modulation under hypoxia. Second, hypoxia enhanced mitochondrial fusion and fission, mitochondrial biosynthesis, and ER quality control in the early stages of hypoxic stress (before 8 h). Third, hypoxia modulated tricarboxylic acid (TCA) cycle flux and caused the accumulation of TCA intermediate metabolites (citric acid and oxoglutaric acid). Additionally, Ca2+ efflux in the ER was observed., and the genes for Ca2+ transporters presented high expression levels in cellular and mitochondrial membranes. Collectively, the above physiological responses of the mitochondria and ER contributed to maintaining energy production to withstand the hypoxic stress in largemouth bass. These results provide novel insights into the physiological and metabolic changes in largemouth bass under hypoxic conditions.

The role of pulmonary mast cells activation and degranulation in the process of increased pulmonary artery pressure.

Hypoxia exposure often cause the increases of pulmonary arterial pressure (PAP). Studies reported that mast cells (MCs) participate in pulmonary vascular remodeling and promote the formation of chronic pulmonary hypertension. Current studies mainly focus on the change of MCs under chronic hypoxia, but few studies on the regulatory role and mechanism of MCs under acute hypoxia. Therefore, present study investigated the dynamic change of MCs in lung tissues under acute hypoxia and the role of MCs activation in the increasement of PAP. In our study, we established an experimental rat model of acute hypobaric hypoxia using a hypobaric chamber (simulated altitude of 7,000 m) and pretreated with MCs degranulation inhibitor sodium cromoglycate (SCG) to study the MCs changes under acute hypoxic exposure. We found that acute hypobaric hypoxia contributed to the increased quantity, activity, and degranulation of MCs and SCG pretreatment showed attenuated PAP elevation under acute hypoxia. Our findings implied that there is a possible mechanism of acute hypoxia cause rapid recruitment of MCs, activation, and explosive degranulation to release Tryptase, Chymase, IL-6, His, 5-HT, and Ang II, which further contributed to pulmonary microvascular contraction and increase in PAP. This work extends the knowledge about MCs, providing a potential profile of MCs as an alternative treatment for high-altitude pulmonary edema (HAPE)-related increased pulmonary artery pressure.

Is NADPH Critical to Maintain Redox Homeostasis in Hypoxia-Tolerant Naked Mole-Rat Brain?

Nicotinamide adenine dinucleotide phosphate (NADPH) is a ubiquitous electron donor and a key reducing agent in numerous biochemical reactions. Among other important cellular roles, NADPH activity is central to the maintenance of redox homeostasis in eukaryotic cells. NADPH increases markedly during acute in vivo hypoxia in the brain of naked mole-rats, which are among the most hypoxia-tolerant mammals, and which do not exhibit imbalances in redox homeostasis or increased reactive oxygen species (ROS)-mediated damage during bouts of hypoxia-reoxygenation in brain. Conversely, NADPH does not increase in the brain of hypoxia-intolerant mice, which are prone to deleterious ROS bursts during perturbations in oxygen availability. Although the importance of NADPH in mediating ROS homeostasis has been demonstrated in the brain of other mammals, little is known about the source of NADPH changes in hypoxic naked mole-rat brain, nor about the mechanisms via which NADPH may provide neuroprotection in this species. Elucidating the underlying mechanisms that support the remarkably stable ROS profile in naked mole-rat brain may provide insight into novel mechanisms to ameliorate the deleterious impact of ROS bursts in the brains of hypoxia-intolerant mammals, such as occur during stroke and other diseases. In this review, we discuss what is known regarding the management of ROS and NADPH in naked mole-rat brain, examine potential cellular sources of NADPH that may underlie the large hypoxic increase in this molecule during acute hypoxic exposure, and propose experiments to advance our understanding of the role NADPH has in maintaining naked mole-rat brain redox balance. (First online: December 28, 2022)

Role of extracellular vesicles derived by human gingival mesenchymal stem cells in cardiomyocytes acute hypoxia

Hypoxia has an impact on pathological conditions of different tissues and especially on the heart where it can have different consequences depending on the duration of exposure to the hypoxic state. Acute hypoxic exposure can result in reversible acclimatization in heart tissue, maintaining a good systemic oxygen supply, while chronic hypoxic exposure leads to tissue damage exacerbating hypoxia-induced cardiac dysfunction. Extracellular vesicles (EVs) are small membrane vesicles, of the order of nanometers, secreted by different cell types. EVs are mediators of intercellular communication in both physiological and pathological conditions. EVs produced by oral-cavity-derived Mesenchymal Stem Cells (MSCs), including human gingival mesenchymal stem cells, have pro-angiogenic and anti-inflammatory effects. For this reason, the EVs can be identify as a new therapeutic potential for tissue regeneration. The aim of the present work was to evaluate the effect of treatment with EVs produced by human gingival mesenchymal stem cells (hGMSCs) on an in vitro model of HL-1 cardiomyocytes cultured under acute hypoxia state (0,2% hypoxia) followed by normoxia conditions. The HIF-1α expression was downregulate with EVs treatment. EVs could represent an innovative platform to prevent the hypoxic damages.

Enhance energy supply of largemouth bass (Micropterus salmoides) in gills during acute hypoxia exposure.

Gills are the location of gas exchange and also the first target organ of fish response for environmental stress. As a multifunctional organ, its energy supply, when faced with insufficient dissolved oxygen in the water, remains unclear. In this study, largemouth bass was subjected to hypoxia stress (1.2mg/L) for 24h and 12h reoxygenation (R12) to evaluate energy supply strategy of gills. Under hypoxia exposure, the respiratory rate of largemouth bass increased by an average of 20 breaths per minute. A total of 2026, 1744, 1003, 579, 485, and 265 differentially expressed genes (DGEs) were identified at 0h, 4h, 8h, 12h, 24h, and R12h in gills after hypoxia exposure. KEGG functional analysis of DEGs revealed that the glycolysis/gluconeogenesis pathway was enriched across all the sampling points (0, 4, 8, 12, 24h, R12). The gene expression and enzyme activity of three rate-limiting enzymes (hexokinase, phosphofructokinase-6, pyruvate kinase) in glycolysis pathway were significantly increased. Increased levels of glycolysis products pyruvate and lactic acid, as well as the number of mitochondria (1.8-fold), suggesting an enhancement of aerobic and anaerobic metabolism of glucose in gills. These results suggest that the gill of largemouth bass enhanced the energy supply during acute exposure to hypoxia stress.

Effect of Biantie pretreatment on serum level of PHD2/HIF-1α and brain tissue damage in rats during acute hypobaric hypoxia exposure

To observe the effect of Biantie (bian stone plaste) pretreatment on serum level of prolyl hydroxylase domain 2 (PHD2) and hypoxia-inducible factor-1α (HIF-1α) in rats with acute hypobaric hypoxia induced-brain injury, and to explore the possible mechanism of Biantie on preventing brain injury at high altitude. Forty-five male SD rats were randomly divided into a blank group, a model group, a Biantie group, a medication group and a Biantie+inhibitor group, 9 rats in each group. The rats in the Biantie group the and the Biantie+inhibitor group were pretreated with Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9), 2 h each time, once a day; the rats in the medication group were treated with intragastric administration of rhodiola capsule solution (280 mg/kg) for 14 d; the rats in the Biantie+inhibitor group were intraperitoneally injected with the PHD inhibitor dimethyloxalyl glycine (DMOG) at a dose of 40 mg/kg 24 h before the establishment of the model. After the intervention, except for the blank group, the rats in the remaining 4 groups were placed in the oxygen chamber to simulate a high-altitude environment to establish the acute hypobaric hypoxia brain injury model. The arterial blood-gas analysis indexes [blood oxygen saturation (SaO2), lactic acid (Lac), blood sodium (Na+), blood potassium (K+)] and brain water content were detected in each group; the histomorphology of cerebral cortex was observed by HE staining; the serum levels of PHD2 and HIF-1α as well as vascular endothelial growth factor (VEGF) were detected by ELISA; the VEGF protein expression in brain tissue was detected by Western blot; the VEGF mRNA expression in brain tissue was detected by real-time fluorescent quantitative PCR. Compared with the blank group, the levels of SaO2 and Na+ in the model group were decreased (P<0.05), while the levels of Lac and K+ as well as the water content of brain tissue were increased (P<0.05). Compared with the model group, the level of SaO2 in the Biantie group and the medication group was increased (P<0.05), while the levels of Lac, K+ and the water content of brain tissue were decreased (P<0.05); the level of Na+ in the Biantie group was increased (P<0.05). Compared with the Biantie group, the level of SaO2 in the Biantie+inhibitor group was decreased (P<0.05), and the level of Lac and the water content of brain tissue were increased (P<0.05). In the model group, the cortical tissue cells were loose and disordered, the cortical blood vessels were dilated, and the cells were obviously swollen; the anoxic injury in the Biantie group and the medication group was lighter, and the anoxic injury in the Biantie+inhibitor group was more obvious than that in the Biantie group. Compared with the blank group, the serum PHD2 content in the model group was decreased and the HIF-1α content was increased (P<0.05), and the content of VEGF in serum and VEGF protein and mRNA expressions in brain were increased (P<0.05). Compared with the model group, the content of PHD2 in serum in the Biantie group and the medication group was increased (P<0.05), and the level of HIF-1α was decreased (P<0.05), and the content of VEGF in serum as well as VEGF protein and mRNA expressions in brain were decreased (P<0.05). Compared with the Biantie group, the serum PHD2 content in the Biantie+inhibitor group was decreased and HIF-1α level were increased (P<0.05), and the content of VEGF in serum as well as VEGF mRNA expression in brain were increased (P<0.05). Biantie at "Taiyuan" (LU 9), "Neiguan" (PC 6) and "Renying" (ST 9) could regulate serum PHD2/HIF-1α to down-regulate VEGF expression, reduce brain edema and enhance anti-hypoxia ability, so as to achieve the purpose of preventing brain injury at high altitude.