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Purpose: The purpose of this study was to evaluate the accuracy of peripheral oxygen saturation (SpO2) measurements from Polar Elixir™ pulse oximetry technology compared with arterial oxygen saturation (SaO2) measurements during acute stepwise steady-state inspired hypoxia at rest. A post hoc objective was to determine if SpO2 measurements could be improved by recalibrating the Polar Elixir™ algorithm with SaO2 values from a random subset of participants. Methods: The International Organization for Standardization (ISO) protocol (ISO 80601-2-61:2017) for evaluating the SpO2 accuracy of pulse oximeter equipment was followed whereby five plateaus of SaO2 between 70% and 100%were achieved using stepwise reductions in inspired O2 during supine rest. Blood samples drawn through a radial arterial catheter from 25 participants were first used to compare SaO2 with SpO2 measurements from Polar Elixir™. Then the Polar Elixir™ algorithm was recalibrated using SaO2 data from 13 random participants, and SpO2 estimates were recalculated for the other 12 participants. For SaO2 values between 70%and 100%, root mean square error, intraclass correlation coefficients (ICC), Pearson correlations, and Bland--Altman plots were used to assess the accuracy, agreement, and strength of relationship between SaO2 values and SpO2 values from Polar Elixir™. Results: The initial root mean square error for Polar Elixir™ was 4.13%. After recalibrating the algorithm, the RMSE was improved to 2.67%. The ICC revealed excellent levels of agreement between SaO2 and Polar Elixir™SpO2 values both before (ICC(1,3) = 0.837, df = 574, P < 0.001) and after (ICC(1,3) = 0.942, df = 287, P < 0.001) recalibration. Conclusions: Relative to ISO standards, Polar Elixir™ yielded accurate SpO2 measurements during stepwise inspired hypoxia at restwhen comparedwith SaO2 values, which were improved by recalibrating the algorithm using a subset of the SaO2 data. [ABSTRACT FROM AUTHOR]

Neural cell damage is an important cause of exacerbation of depression symptoms caused by hypoxia, but the mechanism behind it is still unclear. The purpose of this study is to elucidate the role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)/mitofusin-2 (MFN2) signaling axis in the development of depression in mice under hypoxia.

We sought to determine the effects of acute simulated altitude on the maximal lactate steady state (MLSS) and physiological responses to cycling at and 10 W above the MLSS-associated power output (PO) (MLSSp and MLSSp+10, respectively). Eleven (4 females) participants (means [SD]; 28 [4] yr; V̇ o 2max: 54.3 [6.9] mL·kg−1·min−1) acclimatized to ∼1,100 m performed 30-min constant PO trials in simulated altitudes of 0 m sea level (SL), 1,111 m mild altitude (MILD), and 2,222 m moderate altitude (MOD). MLSSp, defined as the highest PO with stable (<1 mM change) blood lactate concentration ([BLa]) between 10 and 30 min, was significantly lower in MOD (209 [54] W) compared with SL (230 [56] W; P < 0.001) and MILD (225 [58] W; P = 0.001), but MILD and SL were not different (P = 0.12). V̇ o 2 and V̇ co 2 decreased at higher simulated altitudes due to lower POs (P < 0.05), but other end-exercise physiological responses (e.g., [BLa], ventilation [V̇ e ], heart rate [HR]) were not different between conditions at MLSSp or MLSSp + 10 (P > 0.05). At the same absolute intensity (MLSSp for MILD), [BLa], HR, and V̇E and all perceptual variables were exacerbated in MOD compared with SL and MILD (P < 0.05). Maximum voluntary contraction, voluntary activation, and potentiated twitch forces were exacerbated at MLSSp + 10 relative to MLSSp within conditions (P < 0.05); however, condition did not affect performance fatiguability at the same relative or absolute intensity (P > 0.05). As MLSSp decreased in hypoxia, adjustments in PO are needed to ensure the same relative intensity across altitudes, but common indices of exercise intensity may facilitate exercise prescription and monitoring in hypoxia. NEW & NOTEWORTHY: This study demonstrates the power output and metabolic rate associated with the maximal lactate steady-state (MLSS) decline in response to simulated altitude; however, common indices of exercise intensity remained unchanged when cycling was performed at the work rate associated with MLSS at each simulated altitude. These results support previous studies that investigated the effects of hypoxia on alternative measures of the critical intensity of exercise and will inform exercise prescription/monitoring across altitudes. [ABSTRACT FROM AUTHOR]

This study investigated the responses of glucolipid metabolism in gibel carp, the CAS III strain (A strain, 7.14 ± 0.23 g) and the Dongting strain (DT strain, 7.72 ± 0.54 g), following acute hypoxia/reoxygenation. The effects of hypoxia (0.39 ± 0.02 mg/L) and reoxygenation (8.30 ± 0.30 mg/L) were examined in both strains after exposure for 2 h. The results revealed significantly enhanced PI3K/AKT pathway and AMPK/HIF-1α pathways, along with upregulated expression of glucose-6-phosphatase (g6pase) and lipid synthesis-related genes (acc and fas) in both gibel carp strains following acute hypoxia (P < 0.05). The observed increase in plasma glucose levels during acute hypoxia may be related to elevated expression of g6pase (P < 0.05). Regarding the genotype, the A strain exhibited significantly higher expression of glucose metabolism-related genes (pk and pepck) in the liver compared to the DT strain (P < 0.05). Conversely, the expression of lipid metabolism-related genes (hsl, lpl, pparα, cpt1a, and aco3) were significantly lower in the A strain compared to the DT strain (P < 0.05). In both strains of gibel carp, reoxygenation resulted in significant activation of the PI3K/AKT and AMPK/mTOR pathways, accompanied by upregulated expression of glucose metabolism-related genes (gk, 6pfk, foxo1a, fbpase, and pepck) and lipid synthesis-related genes (srebp-1, acly, and acc) (P < 0.05). Notably, the A strain exhibited increased transcripts of glucose metabolism-related genes (gk, pk, foxo1a, g6pase, and pepck) and lipid metabolism-related genes (acly, fas, and cpt1a) compared to the DT strain (P < 0.05). Overall, this study revealed distinct regulation patterns of glucolipid metabolism in the gibel carp with different genotype under acute hypoxia/reoxygenation.

Background/aim: Ischemic heart diseases continue to be a significant global cardiovascular problem in today's world. Myocardial reperfusion (R) is provided with an effective and rapid treatment; however, it can lead to fatal results, as well as ischemia (I). This study aims to use proteomic analysis to assess proteins and pathways in H9C2 cardiomyoblast cells exposed to hypoxic conditions, followed by reoxygenation, representing I/R injury for both short and long terms, reflecting acute and chronic hypoxia, respectively. Utilizing advanced techniques, our goal is to identify and characterize key proteins undergoing alterations during these critical phases. Materials and methods: H9C2 cardiomyoblasts, a commonly used cell line for simulating in vivo I/R damage, were exposed to normoxia and hypoxia (0.4% O2) in six experimental groups: normoxia (3h), acute hypoxia (3h), acute hypoxia (3h) + reoxygenation (3h), normoxia (21h), chronic hypoxia (21h), and chronic hypoxia (21h) + reoxygenation (3h). Analyses were conducted using Nano LC/MSMS from tryptic digest of the whole cell lysates. Proteins were quantified using the label-free quantification (LFQ) algorithm in Proteome Discoverer 2.4. Results: Proteomic analysis resulted in identification of 2383 protein groups. Proteins that differentially expressed in the various groups were identified (p < 0.05 among mean values for groups). Short-term hypoxia induces mitochondrial damage, energy demand, and cytoskeletal modifications. Chronic hypoxia triggers metabolic shifts, stress-response proteins, and extracellular matrix alterations. Data are available via ProteomeXchange with identifier PXD047994. Conclusion: Our research provides in-depth insights into how H9C2 cardiomyoblasts respond to both short-term and prolonged oxygen deprivation. Understanding hypoxia-related pathophysiology provides avenues for therapeutic intervention in hypoxia-related disorders. [ABSTRACT FROM AUTHOR]

Hypoxia signaling plays an important role in physiological and pathological conditions. Hypoxia in the heart tissue can produce different consequences depending on the duration of exposure to the hypoxic state. While acute hypoxic exposure leads to a reversible acclimatization in heart tissue with normal systemic oxygen supply, chronic hypoxia exacerbates cardiac dysfunction, leads to a destruction of the tissue. Extracellular vesicles (EVs) are small membrane vesicles that act as mediators of intercellular communication. EVs are secreted by different cell types and those produced by oral cavity-derived mesenchymal stem cells (MSCs), including human gingival MSCs (hGMSCs), have pro-angiogenic and anti-inflammatory effects and showed therapeutic role in tissue regeneration. The aim of the present work was to evaluate the potential protective and regenerative role of EVs produced by hGMSCs, in an in vitro model of hypoxia-conditioned HL-1 cardiomyocytes through the expression analysis of following inflammatory, oxidative stress, angiogenesis, cell survival and apoptotic markers: HIF-1α, P300, NFkB, CCL2, IL1B, IL6, NRF2, CASP-3, BAX and VEGF. Results showed that hGMSCs-derived EVs exerted protection HL-1 cardiomyocytes exposed to both pre and post hypoxic conditions. Moreover, modulation of CASP3 and BAX expression demonstrated that EVs reduced the apoptosis. The analysis of microRNAs in EVs derived from hGMSCs was performed to assess the epigenetic regulation of the presented markers. The following microRNAs: hsa-miR-138-5p, hsa-miR-17-5p, hsa-miR-18a-5p, hsa-miR-21-5p, hsa-miR-324-5p, hsa-miR-133a-3p, hsamiR-150-5p, hsa-miR-199a-5p, hsa-miR-128-3p and hsa-miR-221-3p can directly or indirectly target the studied genes by determining their modulation obtained in our study. The data from this study suggested that EVs obtained from hGMSCs may be considered for the cell free treatment option in hypoxia-driven cardiac tissue dysfunction. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Exposure to high ambient altitudes above 10,000 ft (3048 m) over sea level during aviation can present the risk of hypobaric hypoxia. Hypoxia can impair sensory and cognitive functions, degrading performance and leading to mishaps. Military aircrew undergo regular hypoxia familiarization training to recognize their symptoms and understand the consequences of hypoxia. However, over the years, aviators have come to believe that individuals have a "personal hypoxia signature." The idea is that intraindividual variability in symptom experience during repeated exposure is low. In other words, individuals will experience the same symptoms during hypoxia from day to day, year to year. METHODS: We critically reviewed the existing literature on this hypothesis. Most studies that claim to support the notion of a signature only examine group-level data, which do not inform individual-level consistency. Other studies use inappropriate statistical methods, while still others do not control for accuracy of recall over the period of years. To combat these shortcomings, we present a dataset of 91 individuals who completed nearly identical mask-off, normobaric hypoxia exposures days apart. RESULTS: We found that for every symptom on the Hypoxia Symptom Questionnaire, at least half of the subjects reported the symptom inconsistently across repeated exposure. This means that, at best, 50% of subjects did not report the same symptom across exposures. DISCUSSION: These data provide compelling evidence against the existence of hypoxia signatures. We urge that hypoxia familiarization training incorporate these findings and encourage individuals to expect a wide range of hypoxia symptoms upon repeated exposure. [ABSTRACT FROM AUTHOR]

Hypoxia leads to metabolic changes at the cellular, tissue, and organismal levels. The molecular mechanisms for controlling physiological changes during hypoxia have not yet been fully studied. Erythroid cells are essential for adjusting the rate of erythropoiesis and can influence the development and differentiation of immune cells under normal and pathological conditions. We simulated high-altitude hypoxia conditions for mice and assessed the content of erythroid nucleated cells in the spleen and bone marrow under the existing microenvironment. For a pure population of CD71+ erythroid cells, we assessed the production of cytokines and the expression of genes that regulate the immune response. Our findings show changes in the cellular composition of the bone marrow and spleen during hypoxia, as well as changes in the composition of the erythroid cell subpopulations during acute hypoxic exposure in the form of a decrease in orthochromatophilic erythroid cells that are ready for rapid enucleation and the accumulation of their precursors. Cytokine production normally differs only between organs; this effect persists during hypoxia. In the bone marrow, during hypoxia, genes of the C-lectin pathway are activated. Thus, hypoxia triggers the activation of various adaptive and compensatory mechanisms in order to limit inflammatory processes and modify metabolism. [ABSTRACT FROM AUTHOR]

Fish meal and fish oil are important sources of protein and lipid in feeds. The lack of fish meal and fish oil supply has become an important limiting factor for the aquaculture industry. The proportion of fish oil and fish meal used in commercial feeds for farmed fish and crustaceans is continually decreasing, while the carbohydrate content is increasing. Carbohydrates are one of the three major nutrients that provide energy for the body. They have a much lower production price than protein and fat. Starch is a polymeric carbohydrate made from glucose molecules; it is the most commonly used in aquatic feeds and can replace fish meal and fish oil to reduce feed cost. Therefore, it is important to fully explore the nutritional function of carbohydrates for aquaculture. Hypoxia is a common stress in aquaculture, and acute hypoxia may lead to massive mortality of cultured fish in a short period of time resulting in serious economic losses to aquaculture. Therefore, it is crucial to find ways to improve the acute hypoxia tolerance of fish. Fish mainly use glucose for energy under acute hypoxia. Hypoxia inhibits oxidative phosphorylation in mitochondria and activates the anaerobic glycolysis pathway. Glucose degrades to produce lactate and ATP. Carnivorous fishes have limited absorption and utilization capacities to feed carbohydrates, unlike omnivorous fishes. Dextrin is an intermediate starch hydrolysis product, with a molecular weight between starch and glucose; it has good adhesion properties and is more easily digested and absorbed than starch. Therefore, we hypothesized that the use of easily digestible carbohydrate in the feed is an effective way to improve the acute hypoxia tolerance of fish. Takifugu rubripes is loved by Japanese and Korean consumers owing to its delicious taste and high nutritional value. It is a characteristic species of Chinese mariculture fish. It is mainly cultured in a high-density factory, and the dissolved oxygen in the water often relies on water exchange and an oxygenation pump; its gill cover is degraded and is at risk of acute hypoxia. This study determined the effect of the addition of corn starch or dextrin (corn starch hydrolysate) to the feed on growth performance, acute hypoxia survival rate, metabolite content, and the hypoxia inducible factor (HIF) signaling pathway of T. rubripes after 8 weeks of feeding. There were no significant differences in weight gain, feed conversion ratio, hepatosomatic index, viscerosomatic index, condition factor, and body composition between the starch group and the dextrin group (P > 0.05). However, the survival rate during acute hypoxia of the dextrin group was significantly higher than that of the starch group (P < 0.05). There were no significant differences in the liver glycogen and lactate contents, and lactate dehydrogenase A4 (ldha) gene expression between the starch group and dextrin group (P > 0.05) during normoxia. However, the lactate content and ldha gene expression were significantly higher in the liver of the dextrin group than those in the starch group (P < 0.05) during hypoxia. This indicated that feeding dextrin strongly activated anaerobic glycolysis to provide more energy under hypoxia. The serum triglyceride (TG) content significantly increased in the dextrin group compared with the normoxia groups, although the TG content in the serum and liver significantly decreased in the starch group after acute hypoxia (P < 0.05). This suggested that feeding starch promoted lipid catabolism and oxygen consumption. There was no significant difference in the total soluble protein content of the muscle between the starch group and the dextrin group (P > 0.05) during normoxia. However, the total soluble protein content of the muscle decreased in the dextrin group compared with the starch group (P < 0.05) after acute hypoxia. Meanwhile, the total muscle soluble protein content, and the gene expression of liver v-akt murine thymoma viral oncogene homolog 1 (akt1), and mechanistic target of rapamycin kinase (mtor) significantly decreased in the dextrin group after hypoxia compared with the normoxia group. However, the liver mtor gene expression significantly increased in the starch group after hypoxia (P < 0.05). This data demonstrated that protein synthesis was inhibited in the dextrin group under hypoxia. Hypoxia inducible factor (HIF) is the most critical transcription factor in cellular response to hypoxic stress. The dextrin group had higher hypoxia inducible factor 1 subunit alpha like (hif-3α) gene expression in the liver and lower hypoxia inducible factor 1 subunit alpha a (hif-1α) gene expression in the muscle (P < 0.05) compared with the starch group during normoxia. The gene expression of liver hif-1α and hif-3α and muscle hif-1α and vascular endothelial growth factor A (vegfa) significantly increased in the dextrin group compared with the starch group (P < 0.05) during hypoxia. This proved that feeding dextrin strongly activated the HIF signaling pathway under hypoxia. In summary, replacing starch with easily digestible dextrin in the feed did not affect the growth performance. Instead, it activated the HIF signaling pathway and anaerobic glycolysis to provide more energy for fish. Meanwhile, feeding dextrin inhibited lipid catabolism and protein synthesis, and reduced oxygen consumption to improve the acute hypoxia tolerance of T. rubripes. The study provides important guidance for the formulation design of hypoxia-tolerant feed and healthy development of aquaculture.

Hypoxia signaling plays an important role in physiological and pathological conditions. Hypoxia in the heart tissue can produce different consequences depending on the duration of exposure to the hypoxic state. While acute hypoxic exposure leads to a reversible acclimatization in heart tissue with normal systemic oxygen supply, chronic hypoxia exacerbates cardiac dysfunction, leads to a destruction of the tissue. Extracellular vesicles (EVs) are small membrane vesicles that act as mediators of intercellular communication. EVs are secreted by different cell types and those produced by oral cavity-derived mesenchymal stem cells (MSCs), including human gingival MSCs (hGMSCs), have pro-angiogenic and anti-inflammatory effects and showed therapeutic role in tissue regeneration. The aim of the present work was to evaluate the potential protective and regenerative role of EVs produced by hGMSCs, in an in vitro model of hypoxia-conditioned HL-1 cardiomyocytes through the expression analysis of following inflammatory, oxidative stress, angiogenesis, cell survival and apoptotic markers: HIF-1α, P300, NFkB, CCL2, IL1B, IL6, NRF2, CASP-3, BAX and VEGF. Results showed that hGMSCs-derived EVs exerted protection HL-1 cardiomyocytes exposed to both pre and post hypoxic conditions. Moreover, modulation of CASP3 and BAX expression demonstrated that EVs reduced the apoptosis. The analysis of microRNAs in EVs derived from hGMSCs was performed to assess the epigenetic regulation of the presented markers. The following microRNAs: hsa-miR-138-5p, hsa-miR-17-5p, hsa-miR-18a-5p, hsa-miR-21-5p, hsa-miR-324-5p, hsa-miR-133a-3p, hsa-miR-150-5p, hsa-miR-199a-5p, hsa-miR-128-3p and hsa-miR-221-3p can directly or indirectly target the studied genes by determining their modulation obtained in our study. The data from this study suggested that EVs obtained from hGMSCs may be considered for the cell free treatment option in hypoxia-driven cardiac tissue dysfunction.

Simple Summary: The greater amberjack (Seriola dumerili) is an economically important fish with high farming value. This species is intolerant to hypoxia, which makes it susceptible to mass mortality and hinders the progress of amberjack cultivation. Based on a comparative analysis of the liver transcriptome between acute hypoxia-tolerant (HT) and intolerant (HS) groups, this study first explored the molecular mechanisms of acute hypoxia in greater amberjack. The results showed that the glycolipid metabolism, antioxidant activity, and apoptotic pathways of greater amberjack significantly responded when exposed to acute hypoxia. In addition, the relative downregulation of apoptosis and autophagy-related genes, such as endog, hm13, and casp6, was also detected in the HT group. The NF-kB pathway was partly promoted in the HT group relative to the HS group to resist apoptosis. This investigation will offer significant technical assistance in the prevention of death caused by acute hypoxia and the subsequent reduction in financial losses. Acute hypoxia is a common abiotic stress in commercial aquaculture and has significant effects on fish physiology and metabolism. Due to its large size and rapid growth, the greater amberjack (Seriola dumerili) is an economically important fish with high farming value. This species is intolerant to hypoxia, which makes it susceptible to mass mortality and hinders the progress of amberjack cultivation. Based on a comparative analysis of the liver transcriptome between acute hypoxia-tolerant (HT) and -intolerant (HS) groups, this study first explored the molecular mechanisms of acute hypoxia in greater amberjack. By simulating the acute hypoxic environment and using RNA sequencing (RNA-Seq), the differences in liver transcriptional changes between the acute hypoxia-tolerant (HT) and hypoxia-intolerant (HS) groups of greater amberjack were probed. Based on differential expression analysis, 829 differentially expressed genes (DEGs) were screened in both groups. Relative to the HS group, 374 DEGs were upregulated and 455 were downregulated in the HT group. Compared with the HS group, genes such as slc2a5 and prkaa2 related to promoting sugar transport and inhibiting lipid syntheses were upregulated, while genes that inhibit gluconeogenesis and promote lipid syntheses, such as pgp and aacs, were downregulated. The expression of odc1 was significantly and relatively downregulated in the HT group, which would lead to the inhibition of intracellular antioxidant activity and decreased scavenging of ROS. The NF-kB pathway was also promoted to some extent in individuals in the HT group relative to the HS group to resist apoptosis. In addition, the relative downregulation of apoptosis and autophagy-related genes, such as endog, hm13, and casp6, was also detected in the HT group. The present findings first reported the regulation mechanism by which liver tissue coped with the acute hypoxia stress in greater amberjack, which will provide important technical support for preventing acute hypoxia-induced death in advance and reducing economic losses. [ABSTRACT FROM AUTHOR]

Abstract Background Despite constant advances in regenerative medicine, the closure of chronic wounds is still challenging. Therapeutic approaches using locally administered MSCs have been considered a promising option. However, the viability of these cells is seriously threatened by acute hypoxic stress linked to wound healing. In this work, we aimed to study the tolerance of Menstrual blood-derived stromal cells (MenSCs) to acute hypoxia and their therapeutic paracrine effect. Methods Isolated MenSCs were phenotypically characterized and evaluated in terms of proliferation, viability, and gene expression, under acute hypoxia (AH) compared with conventional cultured condition or normoxia (N). A step further, the secretome of MenSCs under acute hypoxia was analyzed with respect to their miRNAs content and by in vitro functional assays. For the analysis of differences between the two groups, Student’s t-test was performed and one-way ANOVA and Tukey’s multiple comparisons test for multiple groups were used. Results Our results revealed that the viability of MenSCs was not affected under acute hypoxia, although proliferation rate slowed down. Gene analysis revealed 5 up-regulated (BNIP3, ANGPTL4, IL6, IL1B, and PDK1) and 4 down-regulated genes (IDO1, HMOX1, ANGPTL2, and HGF) in AH compared to N. Global gene expression analysis revealed a decrease in the gene ontology functions of migration and wound response with respect to the normoxic condition. In contrast, functions such as angiogenesis were enriched under the AH condition. Regarding the secretome analysis, two miRNAs involved in angiogenic processes (hsa-miR-148a-3p and hsa-miR-378a-3p), were significantly up-expressed when compared to the normoxic condition, being MYC gene, the unique target of both. Functional assays on HUVECs revealed a potential pro-angiogenic capacity of MenSCs cultured in both oxygen conditions (N and AH) based on the wound closure and tube formation results of their released paracrine factors. However, when compared to normoxia, the paracrine factors of MenSCs under acute hypoxia slightly reduced the proliferation, migration, and in vitro wound closure of HUVECs. Conclusions MenSC exhibited a good survival capacity under acute hypoxic conditions as well as beneficial properties applicable in the field of tissue regeneration through their secretome, which makes them a potential cell source for wound healing interventions.

Background: The altering effects of hypoxia on aerobic/anaerobic performance are well documented and form the basis of this study. Application of hyperoxic gases (inspiratory fraction of oxygen [FiO2] > 0.2095) prior to competition or training (hyperoxic preconditioning) can compensate for the negative influence of acute hypoxia. Purpose: To investigate whether oxygen supplementation immediately prior to exercise (FiO2 = 1.0) improves all-out exercise performance in normobaric hypoxia (3500 m) in highly skilled skiers. Methods: In this single-blind, randomized, crossover study, 17 subjects performed a 60-second constant-load, all-out test in a normobaric hypoxic chamber. After a short period of adaptation to hypoxia (60 min), they received either pure oxygen or chamber air for 5 minutes prior to the all-out test (hyperoxic preconditioning vs nonhyperoxic preconditioning). Capillary blood was collected 3 times, and muscle oxygenation was assessed with near-infrared spectroscopy. Results: Absolute and relative peak power (P =.073 vs P =.103) as well as mean power (P =.330 vs P =.569) did not significantly differ after the hyperoxic preconditioning phase. PaO2 increased from 51.3 (3) to 451.9 (89.0) mm Hg, and SaO2 increased from 88.2% (1.7%) to 100% (0.2%) and dropped to 83.8% (4.2%) after the all-out test. Deoxygenation (P =.700) and reoxygenation rates (P =.185) did not significantly differ for both preconditioned settings. Conclusions: Therefore, the authors conclude that hyperoxic preconditioning did not enhance 60-second all-out exercise performance in acute hypoxia (3500 m). [ABSTRACT FROM AUTHOR]

Mitochondria are a main source of cellular energy. Oxidative phosphorylation (OXPHOS) is the major process of aerobic respiration. Enzyme complexes of the electron transport chain (ETC) pump protons to generate a protonmotive force (Δp) that drives OXPHOS. Complex I is an electron entry point into the ETC. Complex I oxidizes nicotinamide adenine dinucleotide (NADH) and transfers electrons to ubiquinone in a reaction coupled with proton pumping. Complex I also produces reactive oxygen species (ROS) under various conditions. The enzymatic activities of complex I can be regulated by metabolic conditions and serves as a regulatory node of the ETC. Complex I ROS plays diverse roles in cell metabolism ranging from physiologic to pathologic conditions. Progress in our understanding indicates that ROS release from complex I serves important signaling functions. Increasing evidence suggests that complex I ROS is important in signaling a mismatch in energy production and demand. In this article, we review the role of ROS from complex I in sensing acute hypoxia.

Hypoxia is a common factor of numerous ocular diseases that lead to dysfunctions and loss of retinal ganglion cells (RGCs) with subsequent vision loss. High-voltageactivated calcium channels are the main source of calcium entry into neurons. Their activity plays a central role in dierent signaling processes in health and diseases, such as enzyme activation, gene transcription, synaptic transmission, or the onset of cell death. This study aims to establish and evaluate the initial eect of the early stage of acute hypoxia on somatic HVA calcium currents in cultured RGCs. HVA calcium currents were recorded in RGCs using the whole-cell patchclamp technique in the voltage-clamp mode. The fast local superfusion was used for a brief (up to 270 s) application of the hypoxic solution (pO2 < 5 mmHg). The switch from normoxic to hypoxic solutions and vice versa was less than 1 s. The HVA calcium channel activity was inhibited by acute hypoxia in 79% of RGCs (30 of 38 RGCs) in a strong voltage-dependent manner. The level of inhibition was independent of the duration of hypoxia or repeated applications. The hypoxiainduced inhibition of calcium currents had a strong correlation with the duration of hypoxia and showed the transition from reversible to irreversible at 75 s of hypoxia and longer. The results obtained are the first demonstration of the phenomena of HVA calcium current inhibition by acute hypoxia in RGCs and provide a conceptual framework for further researc [ABSTRACT FROM AUTHOR]

Oxygen level is an important environmental factor affecting the circadian rhythm. However, little is known about the molecular mechanism by which clock genes regulate the circadian rhythm in fish under hypoxia. To explore changes in the transcription and expression of clock genes and related molecular regulatory mechanisms in pearl gentian grouper under hypoxia, liver transcriptome data were analyzed after exposure to acute hypoxic stress (dissolved oxygen 0.5 mg/L) for 1, 3, 6, and 9 h. miR-210 and m0044-5p inhibited the expression of period3 (per3) and casein kinase 1 delta b (csnk1db) in the core loop of the circadian clock, respectively. The nuclear receptor subfamily 1 group d member 1 (nr1d1) and RAR-related orphan receptor b (rorb) genes in the auxiliary loop were jointly up-regulated by three miRNAs (miR-144-3p/5p, miR-361-5p, and miR-133) and the transcription factor nuclear receptor subfamily 1 group d member 2 (Nr1d2). The pearl gentian grouper maintains the stability of circadian clock systems and normal physiological metabolism under hypoxic stress by regulating the transcriptional expression of these genes via miRNAs and transcription factors to improve hypoxic tolerance. These findings provide important basic data for future research on hypoxic tolerance in pearl gentian grouper and provide new insights into the interaction between hypoxia and the circadian rhythm in fish. [ABSTRACT FROM AUTHOR]

The onset of regular, strong, and progressive uterine contractions may result in both mechanical (compression of the fetal head and/or umbilical cord) and hypoxic (repetitive and sustained compression of the umbilical cord or reduction in uteroplacental oxygenation) stresses to a human fetus. Most fetuses are able to mount effective compensatory responses to avoid hypoxic-ischemic encephalopathy and perinatal death secondary to the onset of anaerobic metabolism within the myocardium, culminating in myocardial lactic acidosis. In addition, the presence of fetal hemoglobin, which has a higher affinity for oxygen even at low partial pressures of oxygen than the adult hemoglobin, especially increased amounts of fetal hemoglobin (ie, 180–220 g/L in fetuses vs 110–140 g/L in adults), helps the fetus to withstand hypoxic stresses during labor. Different national and international guidelines are currently being used for intrapartum fetal heart rate interpretation. These traditional classification systems for fetal heart rate interpretation during labor are based on grouping certain features of fetal heart rate (ie, baseline fetal heart rate, baseline variability, accelerations, and decelerations) into different categories (eg, category I, II, and III tracings, "normal, suspicious, and pathologic" or "normal, intermediary, and abnormal"). These guidelines differ from each other because of the features included within different categories and because of their arbitrary time limits stipulated for each feature to warrant an obstetrical intervention. This approach fails to individualize care because the "ranges of normality" for stipulated parameters apply to the population of human fetuses and not to the individual fetus in question. Moreover, different fetuses have different reserves and compensatory responses and different intrauterine environments (presence of meconium staining of amniotic fluid, intrauterine inflammation, and the nature of uterine activity). Pathophysiological interpretation of fetal heart rate tracing is based on the application of the knowledge of fetal responses to intrapartum mechanical and/or hypoxic stress in clinical practice. Both experimental animal studies and observational human studies suggest that, just like adults undertaking a treadmill exercise, human fetuses show predictable compensatory responses to a progressively evolving intrapartum hypoxic stress. These responses include the onset of decelerations to reduce myocardial workload and preserve aerobic metabolism, loss of accelerations to abolish nonessential somatic body movements, and catecholamine-mediated increases in the baseline fetal heart rate and effective redistribution and centralization to protect the fetal central organs (ie, the heart, brain, and adrenal glands), which are essential for intrauterine survival. Moreover, it is essential to incorporate the clinical context (progress of labor, fetal size and reserves, presence of meconium staining of amniotic fluid and intrauterine inflammation, and fetal anemia) and understand the features suggestive of fetal compromise in nonhypoxic pathways (eg, chorioamnionitis and fetomaternal hemorrhage). It is important to appreciate that the timely recognition of the speed of onset of intrapartum hypoxia (ie, acute, subacute, and gradually evolving) and preexisting uteroplacental insufficiency (ie, chronic hypoxia) on fetal heart rate tracing is crucial to improve perinatal outcomes. [ABSTRACT FROM AUTHOR]

Hypoxia is linked to disease progression and poor prognosis in several cancers, including breast cancer. Cancer cells can encounter acute, chronic, and/or intermittent periods of oxygen deprivation and it is poorly understood how the different breast cancer subtypes respond to such hypoxia regimes. Here, we assessed the response of representative cell lines for the luminal and basal A subtype to acute (24 h) and chronic hypoxia (5 days). High throughput targeted transcriptomics analysis showed that HIF-related pathways are significantly activated in both subtypes. Indeed, HIF1⍺ nuclear accumulation and activation of the HIF1⍺ target gene CA9 were comparable. Based on the number of differentially expressed genes: (i) 5 days of exposure to hypoxia induced a more profound transcriptional reprogramming than 24 h, and (ii) basal A cells were less affected by acute and chronic hypoxia as compared to luminal cells. Hypoxia-regulated gene networks were identified of which hub genes were associated with worse survival in breast cancer patients. Notably, while chronic hypoxia altered the regulation of the cell cycle in both cell lines, it induced two distinct adaptation programs in these subtypes. Mainly genes controlling central carbon metabolism were affected in the luminal cells whereas genes controlling the cytoskeleton were affected in the basal A cells. In agreement, in response to chronic hypoxia, lactate secretion was more prominently increased in the luminal cell lines which were associated with the upregulation of the GAPDH glycolytic enzyme. This was not observed in the basal A cell lines. In contrast, basal A cells displayed enhanced cell migration associated with more F-actin stress fibers whereas luminal cells did not. Altogether, these data show distinct responses to acute and chronic hypoxia that differ considerably between luminal and basal A cells. This differential adaptation is expected to play a role in the progression of these different breast cancer subtypes. [ABSTRACT FROM AUTHOR]

Background: Despite constant advances in regenerative medicine, the closure of chronic wounds is still challenging. Therapeutic approaches using locally administered MSCs have been considered a promising option. However, the viability of these cells is seriously threatened by acute hypoxic stress linked to wound healing. In this work, we aimed to study the tolerance of Menstrual blood-derived stromal cells (MenSCs) to acute hypoxia and their therapeutic paracrine effect. Methods: Isolated MenSCs were phenotypically characterized and evaluated in terms of proliferation, viability, and gene expression, under acute hypoxia (AH) compared with conventional cultured condition or normoxia (N). A step further, the secretome of MenSCs under acute hypoxia was analyzed with respect to their miRNAs content and by in vitro functional assays. For the analysis of differences between the two groups, Student's t-test was performed and one-way ANOVA and Tukey's multiple comparisons test for multiple groups were used. Results: Our results revealed that the viability of MenSCs was not affected under acute hypoxia, although proliferation rate slowed down. Gene analysis revealed 5 up-regulated (BNIP3, ANGPTL4, IL6, IL1B, and PDK1) and 4 down-regulated genes (IDO1, HMOX1, ANGPTL2, and HGF) in AH compared to N. Global gene expression analysis revealed a decrease in the gene ontology functions of migration and wound response with respect to the normoxic condition. In contrast, functions such as angiogenesis were enriched under the AH condition. Regarding the secretome analysis, two miRNAs involved in angiogenic processes (hsa-miR-148a-3p and hsa-miR-378a-3p), were significantly up-expressed when compared to the normoxic condition, being MYC gene, the unique target of both. Functional assays on HUVECs revealed a potential pro-angiogenic capacity of MenSCs cultured in both oxygen conditions (N and AH) based on the wound closure and tube formation results of their released paracrine factors. However, when compared to normoxia, the paracrine factors of MenSCs under acute hypoxia slightly reduced the proliferation, migration, and in vitro wound closure of HUVECs. Conclusions: MenSC exhibited a good survival capacity under acute hypoxic conditions as well as beneficial properties applicable in the field of tissue regeneration through their secretome, which makes them a potential cell source for wound healing interventions. [ABSTRACT FROM AUTHOR]

Hypoxia is a common factor of numerous ocular diseases that lead to dysfunctions and loss of retinal ganglion cells (RGCs) with subsequent vision loss. High-voltage-activated calcium channels are the main source of calcium entry into neurons. Their activity plays a central role in different signaling processes in health and diseases, such as enzyme activation, gene transcription, synaptic transmission, or the onset of cell death. This study aims to establish and evaluate the initial effect of the early stage of acute hypoxia on somatic HVA calcium currents in cultured RGCs. HVA calcium currents were recorded in RGCs using the whole-cell patch-clamp technique in the voltage-clamp mode. The fast local superfusion was used for a brief (up to 270 s) application of the hypoxic solution (pO2 < 5 mmHg). The switch from normoxic to hypoxic solutions and vice versa was less than 1 s. The HVA calcium channel activity was inhibited by acute hypoxia in 79% of RGCs (30 of 38 RGCs) in a strong voltage-dependent manner. The level of inhibition was independent of the duration of hypoxia or repeated applications. The hypoxia-induced inhibition of calcium currents had a strong correlation with the duration of hypoxia and showed the transition from reversible to irreversible at 75 s of hypoxia and longer. The results obtained are the first demonstration of the phenomena of HVA calcium current inhibition by acute hypoxia in RGCs and provide a conceptual framework for further research.

Dissolved oxygen (DO) is an essential ecological factor encountered by fish and other aquatic animals, and hypoxia can adversely affect the physiology, biochemistry and behavior of aquatic animals. Blood is an essential tissue for oxygen transportation and plays a key role in maintaining homeostasis and adapting the organism to hypoxia. However, studies focusing on the molecular regulatory mechanisms of blood under hypoxia are scant. Therefore, to explore the hypoxia adaptive mechanisms in the blood, we used RNA-Seq technology to investigate the transcriptome changes in the blood of Takifugu rubripes under acute hypoxia. In our study, 20 fish were selected and divided into four groups, including a control group (PPM5.4) and three experimental groups (PPM4, PPM2 and PPM0). In addition to GO and KEGG enrichment analysis, we further used GSEA enrichment analysis to screen the pathways mediated in T. rubripes under hypoxia. Results revealed that hypoxia had a greater effect on blood than other tissues, and T. rubripes could inhibit cell proliferation and down-regulated immune-related pathways (including IL-17 signaling pathway, C-type lectin receptor signaling pathway, B cell receptor signaling pathway and Toll-like receptor signaling pathway). However, the blood of T. rubripes could positively modulate the genes expression involved in energy regulation, angiogenesis and oxidative stress to resist hypoxic damage. Furthermore, T. rubripes could also up-regulate apoptosis and JAK−STAT signaling pathway to conduct self-protection in response to hypoxia. In conclusion, all these results indicated that immune processes, energy metabolism, angiogenesis and oxidative stress were significantly altered in the blood of acute hypoxic T. rubripes, which contributed to maintain cellular energy balance and oxygen supply during hypoxic conditions. The key regulatory genes and pathways identified in this study not only reveal the mechanism of hypoxia tolerance in T. rubripes, but also provide a theoretical basis for breeding hypoxia-tolerant T. rubripes and other fish.

Hypoxia leads to metabolic changes at the cellular, tissue, and organismal levels. The molecular mechanisms for controlling physiological changes during hypoxia have not yet been fully studied. Erythroid cells are essential for adjusting the rate of erythropoiesis and can influence the development and differentiation of immune cells under normal and pathological conditions. We simulated high-altitude hypoxia conditions for mice and assessed the content of erythroid nucleated cells in the spleen and bone marrow under the existing microenvironment. For a pure population of CD71+ erythroid cells, we assessed the production of cytokines and the expression of genes that regulate the immune response. Our findings show changes in the cellular composition of the bone marrow and spleen during hypoxia, as well as changes in the composition of the erythroid cell subpopulations during acute hypoxic exposure in the form of a decrease in orthochromatophilic erythroid cells that are ready for rapid enucleation and the accumulation of their precursors. Cytokine production normally differs only between organs; this effect persists during hypoxia. In the bone marrow, during hypoxia, genes of the C-lectin pathway are activated. Thus, hypoxia triggers the activation of various adaptive and compensatory mechanisms in order to limit inflammatory processes and modify metabolism.

It is well known that acute hypoxia has negative effects on balance performance. An attempt to compensate for the influence of hypoxia on competition performance was made by the application of hyperoxic gases (inspiratory fraction of oxygen > 0.2095) prior to exercise. Purpose: To investigate whether hyperoxic preconditioning (pure-oxygen supplementation prior to exercise) improves balance ability and postural stability during normobaric hypoxia (3500 m) in highly skilled skiers. Methods: In this single-blind randomized, crossover study, 19 subjects perlormed a 60-s balance test (MFT S3-Check) in a normobaric hypoxic chamber. After a short period of adaptation to hypoxia (60 min), they received either pure oxygen or chamber air for 5 min prior to a balance test (hyperoxic preconditioning vs nonhyperoxic preconditioning). Capillary blood was collected 3 times. Results: Balance performance, indexed by sensory (P = .097), stability (P = .937), and symmetry (P = .202) scores, was not significantly different after the hyperoxic preconditioning phase. Balance performance decreased over time (no group difference). After hyperoxic preconditioning, arterial partial pressure of oxygen increased from 52.7 (4.5) mm Hg to 212.5 (75.8) mm Hg, and oxygen saturation of hemoglobin increased from 85.8% (3.5%) to 98.9% (0.7%) and remained significantly elevated to 90.1% (2.0%) after the balance test. Conclusion: A hyperoxic preconditioning phase does not affect balance performance under hypoxic environmental conditions. A performance-enhancing effect, at least in terms of coordinative functions, was not supported by this study. [ABSTRACT FROM AUTHOR]

Background: Sodium bicarbonate injection can prevent brain trauma and serious internal problems. Since brain neuronal damage can be caused by an acute event such as hypoxia or cardio-respiratory arrest, prevention of severe acidosis can protect brain cells. Methods: We used Mus Masculus and BALB / C mice weighing 25 -35 g, aged 8 to 12 weeks old, from the Shohada-e-Tajrish Laboratory Animal Center, Tehran, Iran. Sodium bicarbonate (SB) (4meq / kg) was injected to the mice at different times and the rate of immobility and respiratory arrest induced by acute hypoxia was measured. Result: In the study group, we first developed acute hypoxia inside the anesthesia chamber and completed hypoxia by adding CO2. The experimental group underwent acute hypoxia, and showed slightly longer resistance than the control group. Bicarbonate (4meq / kg, IP) was injected to animals 60 min, 6 h, 12 h, and 24 h before acute hypoxia. Conclusion: In this study, SB at doses above 4meq / kg had a significant effect on hypoxia and led increased resistance to acute hypoxia. [ABSTRACT FROM AUTHOR]

Dünnwald, T, Morawetz, D, Faulhaber, M, Gatterer, H, Birklbauer, C, Koller, A, Weiss, G, and Schobersberger, W. Supplemental O2 during recovery does not improve repeated maximal concentric-eccentric strength-endurance performance in hypoxia. J Strength Cond Res 36(11): 3065–3073, 2022—An alpine ski racing training session typically includes repeated bouts of maximal exercise at high altitude. We evaluated whether hyperoxic recovery between 5 sets of high-intensity strength-endurance exercises, which resembled ski racing activity and were performed in hypoxia, has beneficial effects on performance and acid-base status. In this randomized, single blinded crossover study, 15 highly skilled ski athletes (4 f/11 m; 29.7 ± 5.7 years) performed 5 90 seconds flywheel sets (S) in a normobaric hypoxic chamber (3,500 m). The flywheel sets were separated by 4 15-minute recovery periods. During recovery, subjects received either 100% O2 (hyperoxic setting [HS]) or hypoxic air (nonhyperoxic setting [NHS]; FiO2: 0.146). Performance outcomes (e.g., power output [PO], concentric peak power [Conpeak], and eccentric peak power [Eccpeak]) and physiological parameters (e.g., heart rate, blood gases, and blood lactate) were evaluated. Mean PO, Conpeak, and Eccpeak from S1 to S5 did not differ between settings (146.9 ± 45 W and 144.3 ± 44 W, 266.9 ± 80 W and 271.2 ± 78 W, and 271.0 ± 93 W and 274.1 ± 74 W for HS and NHS, respectively; p ≥ 0.05). SpO2, PaO2, and CaO2 were higher during recovery in HS than in NHS (p ≤ 0.001). Lactate levels were significantly lower in the last recovery phase in HS than in NHS (p = 0.016). Hyperoxic recovery has no impact on performance in a setting resembling alpine ski racing training. Positive effects on arterial oxygen content and cellular metabolism, as indicated by reduced blood lactate levels during recovery in the hyperoxic setting, seem to be insufficient to generate a direct effect on performance. [ABSTRACT FROM AUTHOR]

Hypoxia has been linked to elevated instances of therapeutic resistance in breast cancer. The exposure of proliferating cancer cells to hypoxia has been shown to induce an aggressive phenotype conducive to invasion and metastasis. Regions of the primary tumors in the breast may be exposed to different types of hypoxia including acute, chronic or intermittent. Intermittent hypoxia (IH), also called cyclic hypoxia, is caused by exposure to cycles of hypoxia and reoxygenation (H-R cycles). Importantly, there is currently no consensus amongst the scientific community on the total duration of hypoxia, the oxygen level, and the possible presence of H-R cycles. In this review, we discuss current methods of hypoxia research, to explore how exposure regimes used in experiments are connected to signaling by different hypoxia inducible factors (HIFs) and to distinct cellular responses in the context of the hallmarks of cancer. We highlight discrepancies in the existing literature on hypoxia research within the field of breast cancer in particular and propose a clear definition of acute, chronic, and intermittent hypoxia based on HIF activation and cellular responses: (i) acute hypoxia is when the cells are exposed for no more than 24 h to an environment with 1% O2 or less; (ii) chronic hypoxia is when the cells are exposed for more than 48 h to an environment with 1% O2 or less and (iii) intermittent hypoxia is when the cells are exposed to at least two rounds of hypoxia (1% O2 or less) separated by at least one period of reoxygenation by exposure to normoxia (8.5% O2 or higher). Our review provides for the first time a guideline for definition of hypoxia related terms and a clear foundation for hypoxia related in vitro (breast) cancer research. [ABSTRACT FROM AUTHOR]

Microglia modulate cardiorespiratory activities during chronic hypoxia. It has not been clarified whether microglia are involved in the cardiorespiratory responses to acute hypoxia. Here we investigated this issue by comparing cardiorespiratory responses to two levels of acute hypoxia (13% O2 for 4 min and 7% O2 for 5 min) in conscious unrestrained rats before and after systemic injection of minocycline (MINO), an inhibitor of microglia activation. MINO increased blood pressure but not lung ventilation in the control normoxic condition. Acute hypoxia stimulated cardiorespiratory responses in MINO-untreated rats. MINO failed to significantly affect the magnitude of hypoxia-induced blood pressure elevation. In contrast, MINO tended to suppress the ventilatory responses to hypoxia. We conclude that microglia differentially affect cardiorespiratory regulation depending on the level of blood oxygenation. Microglia suppressively contribute to blood pressure regulation in normoxia but help maintain ventilatory augmentation in hypoxia, which underscores the dichotomy of central regulatory pathways for both systems. [ABSTRACT FROM AUTHOR]

This study investigates whether a functional single nucleotide polymorphism of HMOX2 (heme oxygenase-2) (rs4786504 T>C) is involved in individual chemosensitivity to acute hypoxia, as assessed by ventilatory responses, in European individuals. These responses were obtained at rest and during submaximal exercise, using a standardized and validated protocol for exposure to acute normobaric hypoxia. Carriers of the ancestral T allele (n = 44) have significantly lower resting and exercise hypoxic ventilatory responses than C/C homozygous carriers (n = 40). In the literature, a hypoxic ventilatory response threshold to exercise has been identified as an independent predictor of severe high altitude-illness (SHAI). Our study shows that carriers of the T allele have a higher risk of SHAI than carriers of the mutated C/C genotype. Secondarily, we were also interested in COMT (rs4680 G > A) polymorphism, which may be indirectly involved in the chemoreflex response through modulation of autonomic nervous system activity. Significant differences are present between COMT genotypes for oxygen saturation and ventilatory responses to hypoxia at rest. In conclusion, this study adds information on genetic factors involved in individual vulnerability to acute hypoxia and supports the critical role of the ≪ O2 sensor ≫ - heme oxygenase-2 - in the chemosensitivity of carotid bodies in Humans.

Acute hypoxia is a common abiotic stress in commercial aquaculture and has significant effects on fish physiology and metabolism. Due to its large size and rapid growth, the greater amberjack (Seriola dumerili) is an economically important fish with high farming value. This species is intolerant to hypoxia, which makes it susceptible to mass mortality and hinders the progress of amberjack cultivation. Based on a comparative analysis of the liver transcriptome between acute hypoxia-tolerant (HT) and -intolerant (HS) groups, this study first explored the molecular mechanisms of acute hypoxia in greater amberjack. By simulating the acute hypoxic environment and using RNA sequencing (RNA-Seq), the differences in liver transcriptional changes between the acute hypoxia-tolerant (HT) and hypoxia-intolerant (HS) groups of greater amberjack were probed. Based on differential expression analysis, 829 differentially expressed genes (DEGs) were screened in both groups. Relative to the HS group, 374 DEGs were upregulated and 455 were downregulated in the HT group. Compared with the HS group, genes such as slc2a5 and prkaa2 related to promoting sugar transport and inhibiting lipid syntheses were upregulated, while genes that inhibit gluconeogenesis and promote lipid syntheses, such as pgp and aacs, were downregulated. The expression of odc1 was significantly and relatively downregulated in the HT group, which would lead to the inhibition of intracellular antioxidant activity and decreased scavenging of ROS. The NF-kB pathway was also promoted to some extent in individuals in the HT group relative to the HS group to resist apoptosis. In addition, the relative downregulation of apoptosis and autophagy-related genes, such as endog, hm13, and casp6, was also detected in the HT group. The present findings first reported the regulation mechanism by which liver tissue coped with the acute hypoxia stress in greater amberjack, which will provide important technical support for preventing acute hypoxia-induced death in advance and reducing economic losses.

Oxygen level is an important environmental factor affecting the circadian rhythm. However, little is known about the molecular mechanism by which clock genes regulate the circadian rhythm in fish under hypoxia. To explore changes in the transcription and expression of clock genes and related molecular regulatory mechanisms in pearl gentian grouper under hypoxia, liver transcriptome data were analyzed after exposure to acute hypoxic stress (dissolved oxygen 0.5 mg/L) for 1, 3, 6, and 9 h. miR-210 and m0044-5p inhibited the expression of period3 (per3) and casein kinase 1 delta b (csnk1db) in the core loop of the circadian clock, respectively. The nuclear receptor subfamily 1 group d member 1 (nr1d1) and RAR-related orphan receptor b (rorb) genes in the auxiliary loop were jointly up-regulated by three miRNAs (miR-144-3p/5p, miR-361-5p, and miR-133) and the transcription factor nuclear receptor subfamily 1 group d member 2 (Nr1d2). The pearl gentian grouper maintains the stability of circadian clock systems and normal physiological metabolism under hypoxic stress by regulating the transcriptional expression of these genes via miRNAs and transcription factors to improve hypoxic tolerance. These findings provide important basic data for future research on hypoxic tolerance in pearl gentian grouper and provide new insights into the interaction between hypoxia and the circadian rhythm in fish.

Continuous utero-placental circulation, and patent umbilical blood vessels ensure an uninterrupted transfer of oxygen and nutrients to the fetus as well as clearance of metabolic waste products. The onset of labour characterized by progressive and strong uterine contractions poses a threat to fetal oxygenation as a result of collapsing the spiral arterioles traversing the myometrium to supply the placental bed, and repetitive compression of the blood vessels within the umbilical cord. Human fetuses are equipped with compensatory mechanisms to cope with transient interruptions of blood supply during labour. The ability to compensate may be blunted in cases of poor fetal reserves, increased metabolic demand (macrosomia or maternal fever), and due to non-hypoxic pathways (e.g. chorioamniontis or fetal hypovolumia-hypotension syndrome). Intrapartum fetal surveillance involves prompt recognition of the features that signal the onset of fetal decompensation on the cardiotocograph (CTG) to ensure a timely intervention to avoid hypoxic-ischaemic encephalopathy (HIE) or perinatal deaths. This article summarises a 'physiological approach' to the interpretation of the CTG which, in places, conflicts with other current UK guidance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This experiment simulated the hypoxic environment caused by actual production operations in fish farming (i.e., catching, gathering, transferring, and weighting) to study the effects of acute hypoxic conditions on the physiological and metabolic responses of triploid rainbow trout (O. mykiss). Two groups of fish weighting 590 g were sampled in the normoxia group (dissolved oxygen above 7 mg/L) and hypoxia group (dissolved oxygen ranged from 2 to 5 mg/L for 10 min). The results showed that 1) regarding stress response, hypoxia increased plasma levels of cortisol, heat shock protein 70 (HSP-70), lysozyme, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine phosphokinase (CPK); induced the expression of hepatic genes encoding nuclear factor erythroid 2 related factor 2 (Nrf2), interferon γ (IFN-γ) and interleukin-1β (IL-1β). 2) Regarding metabolism response, hypoxia increased plasma levels of globulin (GLOB), glucose (GLU), triglyceride (TG) and lactate dehydrogenase (LDH); upregulated the hepatic gene expression of phosphoenolpyruvate carboxykinase, (PEPCK), pyruvate dehydrogenase kinase (PDK1), acetyl-CoA carboxylase (ACC) and acetyl-CoA oxidase (ACO); downregulated the hepatic gene expression of carnitine palmitoyl transferase 1 (CPT1); and unchanged the expression of hepatic genes in glycolysis and autophagy. 3) In response to hypoxia-inducible factors (HIFs), the hepatic HIF-2α gene was activated in the hypoxia group, but HIF-1α gene expression remained unchanged. Thus, during acute hypoxic stress, triploid rainbow trout were in a defensive state, with an enhanced immune response and altered antioxidant status. Additionally, the hepatic mitochondrial oxidation of glucose- and lipid-derived carbon in trout was suppressed, and hepatic gluconeogenesis and lipid synthesis were activated, which might be regulated by the HIF-2α pathway. [ABSTRACT FROM AUTHOR]

Hypobaric hypoxia (pO2 65 mm Hg, duration 4 h) induced a significant increase in the number of cardiomyocytes expressing р53, beclin-1, endothelial NO synthase and accumulation and degranulation of mast cells in the epicardium in hearts of prepubertal female rats (age 45-47 days); the number of cardiomyocytes with nucleoli decreased, while the number of single-nucleolar cardiomyocytes increased after this exposure. Five-fold administration of non-opiate analogue of leu-enkephalin (NALE peptide: Phe–D-Ala–Gly–Phe–Leu–Arg; 100 μg/kg) during the neonatal period reduced the severity of the post-hypoxic changes in the heart. Neonatal administration of NALE (100 μg/kg) against the background of NO synthase blockade with L-NAME (50 mg/kg) did not abolish the cardioprotective effects of the peptide. A similar correction of posthypoxic changes in the heart was observed after neonatal administration of original peptide G (Phe–D-Ala–Gly–Phe–Leu–Gly; 100 μg/kg). Thus, NO synthase—NO system and C-terminal amino acid Arg in the molecule of non-opiate analogue of leu-enkephalin are not required for the cardioprotective effects of peptides. Non-opiate leu-enkephalin analogs, peptides NALE and G, can be considered as promising substances for increasing heart resistance to hypoxia during later age periods. [ABSTRACT FROM AUTHOR]

This experiment simulated the hypoxic environment caused by actual production operations in fish farming (i.e., catching, gathering, transferring, and weighting) to study the effects of acute hypoxic conditions on the physiological and metabolic responses of triploid rainbow trout (O. mykiss). Two groups of fish weighting 590 g were sampled in the normoxia group (dissolved oxygen above 7 mg/L) and hypoxia group (dissolved oxygen ranged from 2 to 5 mg/L for 10 min). The results showed that 1) regarding stress response, hypoxia increased plasma levels of cortisol, heat shock protein 70 (HSP-70), lysozyme, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatine phosphokinase (CPK); induced the expression of hepatic genes encoding nuclear factor erythroid 2 related factor 2 (Nrf2), interferon γ (IFN-γ) and interleukin-1β (IL-1β). 2) Regarding metabolism response, hypoxia increased plasma levels of globulin (GLOB), glucose (GLU), triglyceride (TG) and lactate dehydrogenase (LDH); upregulated the hepatic gene expression of phosphoenolpyruvate carboxykinase, (PEPCK), pyruvate dehydrogenase kinase (PDK1), acetyl-CoA carboxylase (ACC) and acetyl-CoA oxidase (ACO); downregulated the hepatic gene expression of carnitine palmitoyl transferase 1 (CPT1); and unchanged the expression of hepatic genes in glycolysis and autophagy. 3) In response to hypoxia-inducible factors (HIFs), the hepatic HIF-2α gene was activated in the hypoxia group, but HIF-1α gene expression remained unchanged. Thus, during acute hypoxic stress, triploid rainbow trout were in a defensive state, with an enhanced immune response and altered antioxidant status. Additionally, the hepatic mitochondrial oxidation of glucose- and lipid-derived carbon in trout was suppressed, and hepatic gluconeogenesis and lipid synthesis were activated, which might be regulated by the HIF-2α pathway.

The suppressor of cytokine signaling (SOCS) gene family is a group of genes involved in the negative regulation of cytokine signal transduction. The members of this family play a crucial role in regulating immune and inflammatory processes. However, comprehensive investigations of these genes have not yet been conducted in the economically significant fish large yellow croaker (Larimichthys crocea). In this study, a total of 13 SOCS genes (LcSOCS1a, LcSOCS1b, LcSOCS2, LcSOCS3a, LcSOCS3b, LcSOCS4, LcSOCS5a, LcSOCS5b, LcSOCS6, LcSOCS7a, LcSOCS7b, LcCISHa and LcCISHb) were identified and analyzed in L. crocea. The phylogenetic tree revealed a high conservation of SOCS genes in evolution, and the gene structure and motif analysis indicated a high similarity in the structure of LcSOCSs in the same subfamily. In addition, the expression patterns of LcSOCSs showed that LcSOCS1b was significantly down-regulated in all time under acute hypoxia stress, but it was markedly up-regulated throughout the entire process after P. plecoglossicida infection, revealing its different immune effects to two stresses. Besides, LcSOCS2a , LcSOCS6 and LcSOCS7a only participated in acute hypoxic stress, while LcSOCS5a was more sensitive to P. plecoglossicida infection. In summary, these results indicated that SOCS genes were involved in stress responses to both biological and non-biological stimuli, setting the foundation for deeper study on the functions of SOCS genes. • A total of 13 SOCS genes were identified in Large yellow croaker. • The phylogenetic relationship of SOCSs were highly conserved in teleost. • LcSOCSs showed significant differential expression respectively in immune responses. • LcSOCSs might regulate immunity responses under Pseudomonas plecoglossicida infection and acute hypoxia stress. [ABSTRACT FROM AUTHOR]

Developing a novel tool capable of real‐time monitoring and simultaneous quantitation of multiple molecules in mitochondria across the whole brain of freely moving animals is the key bottleneck for understanding the physiological and pathological roles that mitochondria play in the brain events. Here we built a Raman fiber photometry, and created a highly selective non‐metallic Raman probe based on the triple‐recognition strategies of chemical reaction, charge transfer, and characteristic fingerprint peaks, for tracking and simultaneous quantitation of mitochondrial O2.−, Ca2+ and pH at the same location in six brain regions of free‐moving animal upon hypoxia. It was found that mitochondrial O2.−, Ca2+ and pH changed from superficial to deep brain regions upon hypoxia. It was discovered that hypoxia‐induced mitochondrial O2.− burst was regulated by ASIC1a, leading to mitochondrial Ca2+ overload and acidification. Furthermore, we found the overload of mitochondrial Ca2+ was mostly attributed to the influx of extracellular Ca2+. [ABSTRACT FROM AUTHOR]

Extremely high temperature and hypoxia are mounting problems affecting the world’s coastal waters under the global warming environment, with severe consequences for marine life. Scallop is one of the most fragile species to hypoxia stress for their high respiration rate and lack of self-protection ability such as long-time shell closing. Circulatory physiology rhythm is sensitive to environmental stress and is an important means for shellfish to quickly respond to environmental stress. Therefore, monitoring the circulatory physiology indexes of Chlamys nobilis under hypoxia and high temperature stress is helpful to quickly diagnose its stress state and reveal the response process of circulatory system to the stress. In this study, using real-time Doppler ultrasonography technique, we continuously monitored the circulatory physiological indexes [heart rate (HR), blood flow volume (FV), blood velocity (PS and ED), resistance index (RI) and S/D ratio) of the scallop organs (gill, mantle and adductor muscle) under hypoxia (mild 4 mg/L DO, moderate 3 mg/L DO and severe 2 mg/L DO)] and fluctuating high temperature stress (29-31°C). Important metabolic function indexes [adenosine triphosphate (ATP), pyruvate kinase (PK) and cytochrome C oxidase (COX)] of various tissues were measured simultaneously. The results show that scallops are very sensitive to the changes of temperature and dissolved oxygen. Both high temperature and hypoxia will increase the HR, and severe hypoxia will bring greater load to the heart of the scallop. Hypoxia stress mainly caused the changes of PS, and the RI and S/D of the gill gradually increased. At 2mg/L DO level, the total blood flow of the mantle and adductor muscle decreased, but the blood flow supply in the gill was stable. The scallop is very sensitive to the change of high temperature and can make adjustments immediately. High temperature increased blood flow in various organs and preferentially supplied to the gill. The RI and S/D of branchial vessels under high temperature were lower than those under hypoxia. The ATP content of the mantle was continuous accumulated under high temperature and was significantly higher than that of the gill and adductor muscle, indicating the specificity of tissue metabolism. The overall circulatory physiological indexes of the gill showed a more positive response to the stress environment than the mantle and adductor muscle. All the results proved that the gill has the best resistance to the hypoxia and high temperature stress. Our study revealed the circulatory physiology regulation mechanism of the noble scallop C. nobilis under environmental stress, and provide effective data and technique supports for the timely diagnose of stress condition of the species, so as to formulate necessary handling strategies for the scallop farm.

To investigate the effects of pathological, physiological, biochemical and metabolic enzymes CYP3A4 on the pharmacokinetics of sildenafil under acute hypoxia, rats were randomly divided into the plain group (50 m above sea level), acute plateau group 1 (2300 m above sea level), and acute plateau group 2 (4300 m above sea level), and blood samples and liver tissues were collected. Our results showed that the blood gas, physiological and biochemical indexes of rats changed under acute hypoxia, and the protein expression of CYP3A4 enzyme decreased. The process of absorption, distribution, metabolism and excretion of sildenafil in rats has changed. Compared with the P group, the area under the drug-time curve and the average resident in the H2 group increased to 213.32 and 72.34%, respectively. The half-life and peak concentration increased by 44.27 and 133.67%, respectively. The clearance rate and apparent distribution volume decreased to 69.13 and 46.75%, respectively. There were no statistical differences in the pharmacokinetic parameters between the P group and the H1 group. In conclusion, the pharmacokinetic changes of sildenafil have a multi-factor regulation mechanism, and changes in blood gas, pathology, and biochemical indicators and metabolic enzymes affect the absorption, distribution, excretion, and metabolism of sildenafil, respectively. This study provides experimental evidence and new ideas for the rational use of sildenafil under acute hypoxic conditions. Changes in CYP3A4 enzyme expression and biochemical markers under acute hypoxia affect the pharmacokinetics of sildenafil. [ABSTRACT FROM AUTHOR]

Background: Acute hypoxia exposure is associated with an elevation of pulmonary artery pressure (PAP), resulting in an increased hemodynamic load on the right ventricle (RV). In addition, hypoxia may exert direct effects on the RV. However, the RV responses to such challenges are not fully characterized. The aim of this systematic review was to describe the effects of acute hypoxia on the RV in healthy lowland adults. Methods: We systematically reviewed PubMed and Web of Science and article references from 2005 until May 2021 for prospective studies evaluating echocardiographic RV function and morphology in healthy lowland adults at sea level and upon exposure to simulated altitude or high-altitude. Results: We included 37 studies in this systematic review, 12 of which used simulated altitude and 25 were conducted in high-altitude field conditions. Eligible studies reported at least one of the RV variables, which were all based on transthoracic echocardiography assessing RV systolic and diastolic function and RV morphology. The design of these studies significantly differed in terms of mode of ascent to high-altitude, altitude level, duration of high-altitude stay, and timing of measurements. In the majority of the studies, echocardiographic examinations were performed within the first 10 days of high-altitude induction. Studies also differed widely by selectively reporting only a part of multiple RV parameters. Despite consistent increase in PAP documented in all studies, reports on the changes of RV function and morphology greatly differed between studies. Conclusion: This systematic review revealed that the study reports on the effects of acute hypoxia on the RV are controversial and inconclusive. This may be the result of significantly different study designs, non-compliance with international guidelines on RV function assessment and limited statistical power due to small sample sizes. Moreover, the potential impact of other factors such as gender, age, ethnicity, physical activity, mode of ascent and environmental factors such as temperature and humidity on RV responses to hypoxia remained unexplored. Thus, this comprehensive overview will promote reproducible research with improved study designs and methods for the future large-scale prospective studies, which eventually may provide important insights into the RV response to acute hypoxia exposure. [ABSTRACT FROM AUTHOR]

Anxiety‐related diseases are more than twice as common in women than in men, and in women, symptoms may be exacerbated during the late luteal phase of the menstrual cycle. Despite this, most research into the underlying mechanisms, which drives drug development, have been carried out using male animals. In an effort to redress this imbalance, we compared responses of male and female Wistar rats during exposure to two unconditioned threatening stimuli that evoke panic‐related defensive behaviours: confrontation with a predator (Bothrops alternatus) and acute exposure to hypoxia (7% O2). Threatened by venomous snake, male and female rats initially displayed defensive attention, risk assessment, and cautious interaction with the snake, progressing to defensive immobility to overt escape. Both males and females displayed higher levels of risk assessment but less interaction with the predator. They also spent more time in the burrow, displaying inhibitory avoidance, and more time engaged in defensive attention, and non‐oriented escape behaviour. In females, anxiety‐like behaviour was most pronounced in the oestrous and proestrus phases whereas panic‐like behaviour was more pronounced during the dioestrus phase, particularly during late dioestrus. Acute hypoxia evoked panic‐like behaviour (undirected jumping) in both sexes, but in females, responsiveness in late dioestrus was significantly greater than at other stages of the cycle. The results reveal that females respond in a qualitatively similar manner to males during exposure to naturally occurring threatening stimuli, but the responses of females is oestrous cycle dependent with a significant exacerbation of panic‐like behaviour in the late dioestrus phase. [ABSTRACT FROM AUTHOR]

Vignati, Carlo, Massimo Mapelli, Benedetta Nusca, Alice Bonomi, Elisabetta Salvioni, Irene Mattavelli, Susanna Sciomer, Andrea Faini, Gianfranco Parati, and Piergiuseppe Agostoni. A breathtaking lift: sex and body mass index differences in cardiopulmonary response in a large cohort of unselected subjects with acute exposure to high altitude. High Alt Med Biol. 22:379–385, 2021. Background: Every year, thousands of people travel to high altitude and experience hypoxemia. At high altitude, the partial pressure of oxygen decreases. The aim of this observational study was to determine if there is a relationship between anthropometric features and basic cardiorespiratory variables, including oxygen saturation (SpO2), heart rate (HR), and blood pressure (BP), following acute exposure to high altitude. Materials and Methods: At the 3,466 m top of a cableway station, we installed an automated system for measuring peripheral SpO2, HR, BP, height, weight, and body mass index (BMI). Results: Between January and October 2020, out of 4,874 volunteers (age 39.9 ± 15.4 years, male 54.4%), 3,267 provided complete data (1,808 cases during winter and 1,459 during summer). SpO2 was 86.8% ± 6.8%. At multivariable analysis, SpO2 was significantly associated with age, sex, season, BMI, and HR but not with BP. We identified 391 (12%) subjects with SpO2 ≤80%: they were older, with a higher BMI and HR but without sex or BP differences. Finally, winter season was associated with greater frequency of SpO2 ≤80% (13.3% vs. 10.3%, p = 0.008). Conclusion: Our data show that high BMI, older age, and male sex were associated with greater degrees of hypoxemia following exposure to high altitude, particularly during the winter. [ABSTRACT FROM AUTHOR]

Purpose: Following an acute exposure to hypoxia, sympathetic nerve activity remains elevated. However, this elevated sympathetic nerve activity does not elicit a parallel increase in vascular resistance suggesting a blunted sympathetic signaling [i.e. blunted sympathetic neurovascular transduction (sNVT)]. Therefore, we sought to quantify spontaneous sympathetic bursts and related changes in total peripheral resistance following hypoxic exposure. We hypothesized that following hypoxia sNVT would be blunted. Methods: Nine healthy participants (n = 6 men; mean age 25 ± 2 years) were recruited. We collected data on muscle sympathetic nerve activity (MSNA) using microneurography and beat-by-beat total peripheral resistance (TPR) via finger photoplethysmography at baseline, during acute hypoxia and during two periods of recovery (recovery period 1, 0–10 min post hypoxia; recovery period 2, 10–20 min post hypoxia). MSNA burst sequences (i.e. singlets, doublets, triplets and quads+) were identified and coupled to changes in TPR over 15 cardiac cycles as an index of sNVT for burst sequences. A sNVT slope for each participant was calculated from the slope of the relationship between TPR plotted against normalized burst amplitude. Results: The sNVT slope was blunted during hypoxia [Δ 0.0044 ± 0.0014 (mmHg/L/min)/(a.u.)], but unchanged following termination of hypoxia [recovery 1, Δ 0.031 ± 0.0019 (mmHg/L/min)/(a.u.); recovery 2, Δ 0.0038 ± 0.0014 (mmHg/L/min)/(a.u.) compared to baseline (Δ 0.038 ± 0.0015 (L/min/mmHg)/(a.u.)] (main effect of group p = 0.012). Conclusions: Contrary to our hypothesis, we have demonstrated that systemic sNVT is unchanged following hypoxia in young healthy adults. [ABSTRACT FROM AUTHOR]

Introduction: Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system (RAS) that has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). Enhancing ACE2 activity using GSK2586881, a recombinant form of human ACE2, could be beneficial in diseases such as ARDS but may blunt the hypoxic pulmonary vasoconstriction (HPV) response and potentially impact systemic and tissue oxygenation. This study aimed to evaluate the effect of GSK2586881 0.8 mg/kg on HPV response in healthy adult volunteers during exercise under hypoxic conditions. Methods: In this phase I, randomised, double-blind (sponsor open) study, GSK2586881 or placebo was administered as a single intravenous (IV) dose in a two-period crossover design. Treatment periods were separated by a washout period of 3–14 days. The primary endpoint was change from baseline in pulmonary artery systolic pressure (PASP) measured by echocardiography. Secondary endpoints included RAS peptides and oxygen saturation. Results: Seventeen adults aged 18–40 years were randomised to treatment. There were no clinically relevant differences (defined as a reduction of ≥ 5 mmHg) in change from baseline in PASP between GSK2586881 and placebo. GSK2586881 was well tolerated, with no serious adverse events, no worsening of hypoxaemia and no evidence of immunogenicity. The study was terminated early after review of the data, which showed that the predefined success criteria had not been met. Following GSK2586881 administration, levels of the RAS peptide angiotensin II decreased while angiotensin (1-7) increased, as expected, indicating that GSK2586881 was pharmacologically active. Conclusions: A single IV dose of GSK2586881 0.8 mg/kg was well tolerated but did not impact the acute HPV response in healthy volunteers. [ABSTRACT FROM AUTHOR]

BACKGROUND: Severe acute hypoxia results in a rapid deterioration of cognitive functioning and thus poses a risk for human operations in high altitude environments. This study aimed at investigating the effects of oxygen system failure during a highaltitude high-opening (HAHO) parachute jump scenario from 30,000 ft (9144 m) on human physiology and cognitive performance using a noncontact eye-tracking task. METHODS: Nine healthy male volunteers (ages 27–48) were recruited from the Norwegian Special Operations Commandos. Eye-tracking data were collected to derive information on cognitive performance in the context of rapid dynamic changes in pressure altitude while performing a modified King-Devick test. The baseline data was collected at 8000 ft (2438 m) while breathing 100% oxygen during decompression. For every test, the corresponding arterial blood gas analysis was performed. RESULTS: The study subjects endured severe hypoxia, which resulted in significant prolongations of fixation time (range: 284.1–245.6 ms) until 23,397 ft (131 m) and fixation size (range: 34.6–32.4 mm) until 25,389 ft (7739 m) as compared to the baseline (217.6 ± 17.8 ms and 27.2 ± 4.5 mm, respectively). The increase in the saccadic movement and decrease in the saccadic velocity was observed until 28,998 ft and 27,360 ft (8839 and 8339 m), respectively. DISCUSSION: This is the first study to investigate cognitive performance from measured oculometric variables during severe hypobaric hypoxia in a simulated high-altitude airdrop mission scenario. The measurement of altered oculometric variables under hypoxic conditions represents a potential avenue to study altered cognitive performance using noncontact sensors that can derive information and serve to provide the individual with a warning from impending incapacitation. [ABSTRACT FROM AUTHOR]

Background: Acute hypoxia exposure is associated with an elevation of pulmonary artery pressure (PAP), resulting in an increased hemodynamic load on the right ventricle (RV). In addition, hypoxia may exert direct effects on the RV. However, the RV responses to such challenges are not fully characterized. The aim of this systematic review was to describe the effects of acute hypoxia on the RV in healthy lowland adults.Methods: We systematically reviewed PubMed and Web of Science and article references from 2005 until May 2021 for prospective studies evaluating echocardiographic RV function and morphology in healthy lowland adults at sea level and upon exposure to simulated altitude or high-altitude.Results: We included 37 studies in this systematic review, 12 of which used simulated altitude and 25 were conducted in high-altitude field conditions. Eligible studies reported at least one of the RV variables, which were all based on transthoracic echocardiography assessing RV systolic and diastolic function and RV morphology. The design of these studies significantly differed in terms of mode of ascent to high-altitude, altitude level, duration of high-altitude stay, and timing of measurements. In the majority of the studies, echocardiographic examinations were performed within the first 10 days of high-altitude induction. Studies also differed widely by selectively reporting only a part of multiple RV parameters. Despite consistent increase in PAP documented in all studies, reports on the changes of RV function and morphology greatly differed between studies.Conclusion: This systematic review revealed that the study reports on the effects of acute hypoxia on the RV are controversial and inconclusive. This may be the result of significantly different study designs, non-compliance with international guidelines on RV function assessment and limited statistical power due to small sample sizes. Moreover, the potential impact of other factors such as gender, age, ethnicity, physical activity, mode of ascent and environmental factors such as temperature and humidity on RV responses to hypoxia remained unexplored. Thus, this comprehensive overview will promote reproducible research with improved study designs and methods for the future large-scale prospective studies, which eventually may provide important insights into the RV response to acute hypoxia exposure.

To investigate the effects of pathological, physiological, biochemical and metabolic enzymes CYP3A4 on the pharmacokinetics of sildenafil under acute hypoxia, rats were randomly divided into the plain group (50 m above sea level), acute plateau group 1 (2300 m above sea level), and acute plateau group 2 (4300 m above sea level), and blood samples and liver tissues were collected. Our results showed that the blood gas, physiological and biochemical indexes of rats changed under acute hypoxia, and the protein expression of CYP3A4 enzyme decreased. The process of absorption, distribution, metabolism and excretion of sildenafil in rats has changed. Compared with the P group, the area under the drug-time curve and the average resident in the H2 group increased to 213.32 and 72.34%, respectively. The half-life and peak concentration increased by 44.27 and 133.67%, respectively. The clearance rate and apparent distribution volume decreased to 69.13 and 46.75%, respectively. There were no statistical differences in the pharmacokinetic parameters between the P group and the H1 group. In conclusion, the pharmacokinetic changes of sildenafil have a multi-factor regulation mechanism, and changes in blood gas, pathology, and biochemical indicators and metabolic enzymes affect the absorption, distribution, excretion, and metabolism of sildenafil, respectively. This study provides experimental evidence and new ideas for the rational use of sildenafil under acute hypoxic conditions.

Hypoxia in water that caused by reduced levels of oxygen occurred frequently, due to the complex aquatic environment. Hypoxia tolerance for fish depends on a complete set of coping mechanisms such as oxygen perception and gene-protein interaction regulation. The present study examined the short-term effects of hypoxia on the brain in Takifugu rubripes. We sequenced the transcriptomes of the brain in T. rubripes to study their response mechanism to acute hypoxia. A total of 167 genes were differentially expressed in the brain of T. rubripes after exposed to acute hypoxia. Gene ontology and KEGG enrichment analysis indicated that hypoxia could cause metabolic and neurological changes, showing the clues of their adaptation to acute hypoxia. As the most complex and important organ, the brain of T. rubripes might be able to create a self-protection mechanism to resist or reduce damage caused by acute hypoxia stress. [ABSTRACT FROM AUTHOR]