Continuous Hypoxia Research Articles

Perioperative Nutritional Support Case Study for a Patient Undergoing Gluteus Maximus Flap Transfer Surgery for Pressure Ulcer

Pressure ulcers are caused by prolonged pressure on local tissues, leading to continuous ischemia, hypoxia, and malnutrition, resulting in tissue necrosis. Patients with pressure ulcers often experience varying degrees of malnutrition due to gut flora imbalance and a hypercatabolic state. This paper documents the case of a patient with a sacral pressure ulcer admitted to the Department of Burn and Plastic Surgery of the Affiliated Hospital of Qinghai University on November 28, 2023. Clinical nutrition treatment began on the second day of admission, including dietary guidance and enteral nutrition intervention. The patient's nutritional status gradually improved, leading to a successful recovery. By reviewing the nutritional treatment process and clinical outcomes, this case study provides valuable insights into the nutritional management of pressure ulcer patients.

Inhibition of cGAS attenuates neonatal hypoxic-ischemic encephalopathy via regulating microglia polarization and pyroptosis.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a condition causing brain injury in newborns with unclear pathogenesis. Cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway and NOD-like receptor protein 3 (NLRP3) mediated pyroptosis are thought to be involved in the pathological process of HIE, but whether these two mechanisms act independently is still unknown. Therefore, we aim to clarify whether there is any interaction between these two pathways and thus synergistically affects the progression of HIE. The HIE model of neonatal rats was established using the Rice-Vannucci method. The potential therapeutic effect of RU.521 targeting cGAS on HIE was explored through rescue experiment. Twenty-four hours after modeling was selected as observation point, sham + vehicle group, HIE + vehicle group and HIE + RU.521 group were established. A complete medium of BV2 cells was adjusted to a glucose-free medium, and the oxygen-glucose deprivation model was established after continuous hypoxia for 4 hours and reoxygenation for 12 to 24 hours. 2,3,5-triphenyl tetrazolium chloride staining was employed to detect ischemic cerebral infarction in rat brain tissue, and hematoxylin and eosin staining was used to observe tissue injury. Immunofluorescence was applied to monitor the expression of cGAS. Real-time quantitative polymerase chain reaction and western blot were utilized to detect the expression of messenger RNA and protein. cGAS expression was increased in brain tissues of neonatal rats with HIE, and mainly localized in microglia. RU.521 administration reduced infarct size and pathological damage in rat HIE. Moreover, blocking cGAS with RU.521 significantly reduced inflammatory conditions in the brain by down-regulating STING expression, decreasing NLRP3 inflammasome activation and reducing microglial pyroptosis both in vivo and in vitro. Besides, RU.521 promoted the switching of BV2 cells towards the M2 phenotype. This study revealed a link between the cGAS/STING pathway and the NLRP3/GSDMD/pyroptosis pathway in neonatal HIE. Furthermore, the small molecule compound RU.521 can negatively regulate cGAS/STING/NLRP3/pyroptosis axis and promote M2 polarization in microglia, which provides a potential therapeutic strategy for the treatment of neuroinflammation in HIE.

Tissue Oxygenation in Individuals with Spinal Cord Injury: A Pilot Study.

Pressure injuries (PI) are debilitating tissue lesions characterised by slow healing and a high risk of severe infection. These injuries result from continued tissue hypoxia, or low tissue oxygen saturation (StO2), which is a consequence of impaired blood circulation caused by continued pressure against tissue. PI result in significant suffering and a substantial financial burden. Therefore, we aim to develop an effective preventive measure. Persons with spinal cord injury (SCI) are at a high risk for PI due to their impaired mobility and lack of sensation to alert them to danger. The aim was to test the feasibility of an alert system based on StO2 monitoring in persons with SCI using a novel textile-based near-infrared spectroscopy (NIRS) sensor.Sensors consisted of two emission and two detection points, each point comprising eight fibres each with three light-coupling bends. Textile integration of fibres was achieved by stitching on a mass-production stitching machine. Emission fibres were connected to LEDs of 740 nm and 810 nm. Detection fibres were connected to avalanche photodiodes. Sensors were attached to the skin in the high-PI-risk buttocks area covering the bony prominences of the ischial tuberosity. StO2 was measured in three healthy subjects and two subjects with SCI during repeated sitting and pressure recovery phases.Our experiments showed decreases in StO2 in both groups during sitting phases: during low-pressure sitting phases, StO2 decreased on average -0.32%/min in the healthy subjects and at -1.24%/min in the SCI subjects. During high-pressure sitting, these rates increased to -1.16%/min for the healthy subjects and -2.16%/min for the SCI subjects. During recovery phases, StO2 returned towards normal values, but did not always reach the initial baseline. No discomfort or skin irritation was observed.These first measurements show physiologically reasonable StO2 values and demonstrate sufficient comfort while sitting on a sensor with no skin irritation or other adverse effects of sitting on the sensor for over 30 min. The nurses involved were satisfied with the easy-of-use, materials used, and patient safety demonstrated during the study. These results show that it is feasible to develop an alert system for PI prevention using a safe, wearable, textile-based NIRS sensor.

Intermittent normobaric hypoxia alters substrate partitioning and muscle oxygenation in individuals with obesity: implications for fat burning.

This single-blind, crossover study aimed to measure and evaluate the short-term metabolic responses to continuous and intermittent hypoxic patterns in individuals with obesity. Indirect calorimetry was used to quantify changes in resting metabolic rate (RMR), carbohydrate (CHOox, %CHO), and fat oxidation (FATox, %FAT) in nine individuals with obesity pre and post: 1) breathing normoxic air [normoxic sham control (NS-control)], 2) breathing continuous hypoxia (CH), or 3) breathing intermittent hypoxia (IH). A mean peripheral oxygen saturation ([Formula: see text]) of 80-85% was achieved over a total of 45 min of hypoxia. Throughout each intervention, pulmonary gas exchanges, oxygen consumption (V̇o2) carbon dioxide production (V̇co2), and deoxyhemoglobin concentration (Δ[HHb]) in the vastus lateralis were measured. Both RMR and CHOox measured pre- and postinterventions were unchanged following each treatment: NS-control, CH, or IH (all P > 0.05). Conversely, a significant increase in FATox was evident between pre- and post-IH (+44%, P = 0.048). Although the mean Δ[HHb] values significantly increased during both IH and CH (P < 0.05), the greatest zenith of Δ[HHb] was achieved in IH compared with CH (P = 0.002). Furthermore, there was a positive correlation between Δ[HHb] and the shift in FATox measured pre- and postintervention. It is suggested that during IH, the increased bouts of muscle hypoxia, revealed by elevated Δ[HHb], coupled with cyclic periods of excess posthypoxia oxygen consumption (EPHOC, inherent to the intermittent pattern) played a significant role in driving the increase in FATox post-IH.

Neuroprotective Effects of Moderate Hypoxia: A Systematic Review.

Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of studies investigating hypoxia (10-16% O2) for ≥14 days in humans, as well as the neurobiological mechanisms triggered by hypoxia in animals, and suggests optimal treatment protocols to guide future studies. We followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020. Searches were performed on PubMed/MEDLINE, PsycInfo, EMBASE, and the Cochrane Library, in May-September 2023. Two authors independently reviewed the human studies with the following tools: (1) revised Cochrane collaboration's risk of bias for randomized trials 2.0; (2) the risk of bias in nonrandomized studies of interventions. We identified 58 eligible studies (k = 8 human studies with N = 274 individuals; k = 48 animal studies) reporting the effects of hypoxia on cognition, motor function, neuroimaging, neuronal/synaptic morphology, inflammation, oxidative stress, erythropoietin, neurotrophins, and Alzheimer's disease markers. A total of 75% of human studies indicated cognitive and/or neurological benefits, although all studies were evaluated ashigh risk of bias due to a lack of randomization and assessor blinding. Low-dose intermittent or continuous hypoxia repeated for 30-240 min sessions, preferably in combination with motor-cognitive training, produced beneficial effects, and high-dose hypoxia with longer (≥6 h) durations and chronic exposure produced more adverse effects. Larger and methodologically stronger translational studies are warranted.

Ferrostatin-1 attenuates hypoxic-ischemic brain damage in neonatal rats by inhibiting ferroptosis.

Hypoxic-ischemic brain damage (HIBD) is a type of brain damage that is caused by perinatal asphyxia and serious damages the central nervous system. At present, there is no effective drug for the treatment of this disease. Besides, the pathogenesis of HIBD remains elusive. While studies have shown that ferroptosis plays an important role in HIBD, its role and mechanism in HIBD are yet to be fully understood. The HIBD model of neonatal rats was established using the Rice-Vannucci method. A complete medium of PC12 cells was adjusted to a low-sugar medium, and the oxygen-glucose deprivation model was established after continuous hypoxia for 12 h. Laser Doppler blood flow imaging was used to detect the blood flow intensity after modeling. 2,3,5-triphenyl tetrazolium chloride staining was employed to detect ischemic cerebral infarction in rat brain tissue, and hematoxylin and eosin staining and transmission electron microscopy were used to observe brain injury and mitochondrial damage. Immunofluorescence was applied to monitor the expression of GFAP. Real-time quantitative polymerase chain reaction, western blot, and immunofluorescence were utilized to detect the expression of messenger RNA and protein. The level of reactive oxygen species (ROS) in cells was detected using the ROS detection kit. The results showed that ferrostatin-1 (Fer-1) significantly alleviated the brain injury caused by hypoxia and ischemia. Fer-1 significantly increased the expression of SLC3A2, SLC7A11, ACSL3, GSS, and GPX4 (P<0.05) and dramatically decreased the expressions of GFAP, ACSL4, TFRC, FHC, FLC, 4-HNE, HIF-1α, and ROS (P<0.05). Fer-1 inhibits ferroptosis and alleviates HIBD by potentially targeting the GPX4/ACSL3/ACSL4 axis; however, its specific mechanism warrants further exploration.

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.

Intermittent hypoxia protects against hypoxic-ischemic brain damage by inducing functional angiogenesis

Ischemic stroke (IS) induces neurological damage due to cerebrovascular occlusion. Restoring blood perfusion to the ischemic brain area in a timely fashion is the most effective treatment strategy. Hypoxia is an effective way of restoring blood perfusion by improving cerebrovascular microcirculation, while the effect varies greatly depending on hypoxic mode. This study aimed to screen for the optimal hypoxic mode to improve cerebrovascular microcirculation and prevent IS. Here, we found that compared with continuous hypoxia (CH), intermittent hypoxia (IH) significantly improved cerebral blood flow and oxygen saturation in mice without causing neurological impairment. By analyzing cerebrovascular microcirculation from mice, we found that the IH mode (13%, 5*10) with 13% O2, 5 min interval, and 10 cycles per day significantly improved the cerebrovascular microcirculation by promoting angiogenesis without affecting the integrity of the blood-brain barrier. In addition, IH (13%, 5*10) treatment of distal middle cerebral artery occlusion (dMCAO) mice significantly alleviated neurological dysfunction and reduced cerebral infarct volume by improving cerebrovascular microcirculation. CH had none of these positive effects. In summary, our study screened for an appropriate intermittent hypoxic mode that could improve cerebrovascular microcirculation, laying a theoretical foundation for the prevention and treatment of IS in clinical practice.

Continuous, but not intermittent, regimens of hypoxia prevent and reverse ataxia in a murine model of Friedreich's ataxia.

Friedreich's ataxia (FA) is a devastating, multi-systemic neurodegenerative disease affecting thousands of people worldwide. We previously reported that oxygen is a key environmental variable that can modify FA pathogenesis. In particular we showed that chronic, continuous normobaric hypoxia (11% FIO2) prevents ataxia and neurological disease in a murine model of FA, although it did not improve cardiovascular pathology or lifespan. Here, we report the pre-clinical evaluation of seven 'hypoxia-inspired' regimens in the shFxn mouse model of FA, with the long-term goal of designing a safe, practical, and effective regimen for clinical translation. We report three chief results. First, a daily, intermittent hypoxia regimen (16hours 11% O2/8hours 21% O2) conferred no benefit, and was in fact harmful, resulting in elevated cardiac stress and accelerated mortality. The detrimental effect of this regimen is likely due to transient tissue hyperoxia that results when daily exposure to 21% O2 combines with chronic polycythemia, as we could blunt this toxicity by pharmacologically inhibiting polycythemia. Second, we report that more mild regimens of chronic hypoxia (17% O2) confer a modest benefit by delaying the onset of ataxia. Third, excitingly, we show that initiating chronic, continuous 11% O2 breathing once advanced neurological disease has already started can rapidly reverse ataxia. Our studies showcase both the promise and limitations of candidate hypoxia-inspired regimens for FA and underscore the need for additional pre-clinical optimization before future translation into humans.

Hypoxia extends lifespan and neurological function in a mouse model of aging.

There is widespread interest in identifying interventions that extend healthy lifespan. Chronic continuous hypoxia delays the onset of replicative senescence in cultured cells and extends lifespan in yeast, nematodes, and fruit flies. Here, we asked whether chronic continuous hypoxia is beneficial in mammalian aging. We utilized the Ercc1 Δ/- mouse model of accelerated aging given that these mice are born developmentally normal but exhibit anatomic, physiological, and biochemical features of aging across multiple organs. Importantly, they exhibit a shortened lifespan that is extended by dietary restriction, the most potent aging intervention across many organisms. We report that chronic continuous 11% oxygen commenced at 4 weeks of age extends lifespan by 50% and delays the onset of neurological debility in Ercc1 Δ/- mice. Chronic continuous hypoxia did not impact food intake and did not significantly affect markers of DNA damage or senescence, suggesting that hypoxia did not simply alleviate the proximal effects of the Ercc1 mutation, but rather acted downstream via unknown mechanisms. To the best of our knowledge, this is the first study to demonstrate that "oxygen restriction" can extend lifespan in a mammalian model of aging.

Sex matters: Gamete-specific contribution of microRNA following parental exposure to hypoxia in zebrafish

Oxygen availability varies among aquatic environments, and oxygen concentration has been demonstrated to drive behavioral, metabolic, and genetic adaptations in numerous aquatic species. MicroRNAs (miRNAs) are epigenetic modulators that act at the interface of the environment and the transcriptome and are known to drive plastic responses following environmental stressors. An area of miRNA that has remained underexplored is the sex specific action of miRNAs following hypoxia exposure and its effects as gene expression regulator in fishes. This study aimed to identify differences in mRNA and miRNA expression in the F1 generation of zebrafish (Danio rerio) at 1 hpf after either F0 parental male or female were exposed to 2 weeks of continuous (45 %) hypoxia. In general, F1 embryos at 1 hpf demonstrated differences in mRNA and miRNAs expression related to the stressor and to the specific sex of the F0 that was exposed to hypoxia. Bioinformatic pathway analysis of predicted miRNA:mRNA relationships indicated responses in known hypoxia signaling and mitochondrial bioenergetic pathways. This research demonstrates the importance of examining the specific male and female contributions to phenotypic variation in subsequent generations and provides evidence that there is both maternal and paternal contribution of miRNA through eggs and sperm.

Hypoxia and Anoxia Tolerance in Diploid and Triploid Eastern Oysters at High Temperature

Increasing reliance on the use of triploid oysters to support aquaculture production relies on their generally superior growth rate and meat quality over that of diploid oysters. Reports of elevated triploid mortality have generated questions about potential trade-offs between growth and tolerance to environmental stressors. These questions are particularly relevant as climate change, coastal activities, and river management impact water salinity, temperature, nutrients, pH, and oxygen levels within key estuarine oyster growing areas. In particular, the co-occurrence of warm water temperatures and low dissolved oxygen concentration (DO) events are increasingly reported in estuaries, with potentially lethal impacts on sessile, oyster resources. To investigate potential differences in DO tolerance, diploid and triploid market-sized or seed oysters were exposed to continuous normoxia (DO > 5.0 mg L–1), hypoxia (DO < 2.0 mg L–1), and anoxia (DO < 0.5 mg L–1) at 28°C and their mortalities were monitored. The hemolymph of the market-sized oysters was collected to measure cellular and biochemical changes in response to hypoxia and anoxia, whereas their valve movements were also measured. In general, about half of market-sized oysters died within about 1 wk under anoxia (LT50: 5.7–8.9 days) and within about 2 wk under hypoxia (LT50: 11.9–19.4 days) with diploid oysters tending to die faster than triploid oysters. Seed oysters took longer to die than market-sized oysters under both anoxia (LT50: 9.5–12.1 days) and hypoxia (LT50: 21.8–25.0 days) with diploid oysters (LT50: 9.5–11.8 days) dying slightly faster than triploid oysters (LT50: 11.8–12.1 days) under anoxia. Hemolymph pH decreased and plasma calcium and glutathione concentrations increased with decreasing DO, with values under anoxia being different than those under normoxia. Hemocyte density was also lower under anoxia than under either normoxia or hypoxia. Overall, few differences in physiological responses to hypoxia and anoxia were found between diploid and triploid oysters suggesting that ploidy (2N versus 3N) had limited effect on the tolerance and response of eastern oysters to low DO.

Asphyxiation of Metarhizium robertsii during mycelial growth produces conidia with increased stress tolerance via increased expression of stress-related genes

Little is known about the impact of hypoxia and anoxia during mycelial growth on tolerance to different stress conditions of developing fungal conidia. Conidia of the insect-pathogenic fungus Metarhizium robertsii were produced on potato dextrose agar (PDA) medium under normoxia (control = normal oxygen concentrations), continuous hypoxia, and transient anoxia, as well as minimal medium under normoxia. The tolerance of the conidia produced under these different conditions was evaluated in relation to wet heat (heat stress), menadione (oxidative stress), potassium chloride (osmotic stress), UV radiation, and 4-nitroquinoline-1-oxide (=4-NQO genotoxic stress). Growth under hypoxic condition induced higher conidial tolerance of M. robertsii to menadione, KCl, and UV radiation. Transient anoxic condition induced higher conidial tolerance to KCl and UV radiation. Nutritional stress (i.e., minimal medium) induced higher conidial tolerance to heat, menadione, KCl, and UV radiation. However, neither of these treatments induced higher tolerance to 4-NQO. The gene hsp30 and hsp101 encoding a heat shock protein was upregulated under anoxic condition. In conclusion, growth under hypoxia and anoxia produced conidia with higher stress tolerances than conidia produced in normoxic condition. The nutritive stress generated by minimal medium, however, induced much higher stress tolerances. This condition also caused the highest level of gene expression in the hsp30 and hsp101 genes. Thus, the conidia produced under nutritive stress, hypoxia, and anoxia had greater adaptation to stress.

Continuous Hypobaric Hypoxia may Promote Atherosclerosis Progression in Apolipoprotein E-deficient Mice.

Background: Intermittent normobaric hypoxia can promote the progression of atherosclerotic plaques. However, the effect of continuous hypobaric hypoxia (CHH), which is a major feature of high-altitude environment, on atherosclerosis has not been investigated thoroughly. Materials and Methods: After eight weeks of high-cholesterol diet, 30 male ApoE-/- mice were randomly divided into control and CHH groups. Mice in the CHH group lived in a hypobaric chamber with an oxygen content of 10% and air pressure of 364 mmhg (equal to 5,800 m altitude above sea level) for 4 weeks, while mice in the control group lived in normoxia condition. Then all mice were euthanized and the atherosclerotic lesion size and plaque stability in the aortic root were assessed. Intraplaque angiogenesis was characterized by immunostaining of CD31 and endomucin, which are identified as specific markers of vascular endothelial cells. Immunohistochemistry and qRT-PCR were performed to measure inflammatory cytokines. Results: Four weeks of CHH exposure promoted the growth of atherosclerotic lesions (p=0.0017) and decreased the stability of atherosclerotic plaques. In CHH group, plaque smooth muscle cells and collagen contents decreased, while plaque macrophages and lipids contents increased significantly (p<0.001). The contents of CD31 (p=0.0379) and endomucin (p=0.0196) in the plaque was higher in the CHH group and correlated with angiogenesis progression. Further, the content of monocyte chemotactic protein-1 (p=0.0376) and matrix metalloproteinase-2 was significantly higher (p=0.0212) in the CHH group. Conclusions: CHH may accelerate atherosclerosis progression in ApoE-/- mice by promoting angiogenesis and inflammation.

Catecholamines modulate the hypoxic ventilatory response of larval zebrafish (Danio rerio).

The hypoxic ventilatory response (HVR) in fish is an important reflex that aids O2 uptake when low environmental O2 levels constrain diffusion. In developing zebrafish (Danio rerio), the acute HVR is multiphasic, consisting of a rapid increase in ventilation frequency (fV) during hypoxia onset, followed by a decline to a stable plateau phase above fV under normoxic conditions. In this study, we examined the potential role of catecholamines in contributing to each of these phases of the dynamic HVR in zebrafish larvae. We showed that adrenaline elicits a dose-dependent β-adrenoreceptor (AR)-mediated increase in fV that does not require expression of β1-ARs, as the hyperventilatory response to β-AR stimulation was unaltered in adrb1-/- mutants, generated by CRISPR/Cas9 knockout. In response to hypoxia and propranolol co-treatment, the magnitude of the rapidly occurring peak increase in fV during hypoxia onset was attenuated (112±14 breaths min-1 without propranolol to 68±17 breaths min-1 with propranolol), whereas the increased fV during the stable phase of the HVR was prevented in both wild type and adrb1-/- mutants. Thus, β1-AR is not required for the HVR and other β-ARs, although not required for initiation of the HVR, are involved in setting the maximal increase in fV and in maintaining hyperventilation during continued hypoxia. This adrenergic modulation of the HVR may arise from centrally released catecholamines because adrenaline exposure failed to activate (based on intracellular Ca2+ levels) cranial nerves IX and X, which transmit O2 signals from the pharyngeal arch to the central nervous system.

The Role of NO Synthase in the Infarct-Limiting Effect of Urgent and Chronic Adaptation to Normobaric Hypoxia.

We studied the role of NO synthase in the infarct-limiting effect of short-term (SNH) and chronic continuous normobaric hypoxia (CNH). In male Wistar rats, SNH (6 sessions of 10-min hypoxia 8% O2 and 10-min reoxygenation) or CNH (12% O2 for 21 days) was modeled. In 30 min after SNH or 24 h after CNH, the rats were subjected to coronary artery occlusion (45 min) and reperfusion (2 h). The following drugs were administered to rats: non-selective NO synthase inhibitor L-NAME (10 mg/kg), inhibitor of inducible NO synthase S-methylthiourea (3 mg/kg), and inhibitor of neuronal NO-synthase 7-nitroindazole (50 mg/kg). NO donor diethylenetriamine was administered intravenously in a dose 2 mg/kg. It was found that L-NAME and S-methylthiourea abolished the infarct-limiting effect of SNH and CNH. Diethylenetriamine increased cardiac tolerance to ischemia/reperfusion. It is believed that inducible NO synthase plays an important role in the cardioprotective effect of normobaric hypoxia.

Continuous Hypoxia Reduces Retinal Ganglion Cell Degeneration in a Mouse Model of Mitochondrial Optic Neuropathy.

To test whether continuous hypoxia is neuroprotective to retinal ganglion cells (RGCs) in a mouse model of mitochondrial optic neuropathy. RGC degeneration was assessed in genetically modified mice in which the floxed gene for the complex I subunit NDUFS4 is deleted from RGCs using Vlgut2-driven Cre recombinase. Beginning at postnatal day 25 (P25), Vglut2-Cre;ndufs4loxP/loxP mice and control littermates were housed under hypoxia (11% oxygen) or kept under normoxia (21% oxygen). Survival of RGC somas and axons was assessed at P60 and P90 via histological analysis of retinal flatmounts and optic nerve cross-sections, respectively. Retinal tissue was also assessed for gliosis and neuroinflammation using western blot and immunofluorescence. Consistent with our previous characterization of this model, at least one-third of RGCs had degenerated by P60 in Vglut2-Cre;ndufs4loxP/loxP mice remaining under normoxia. However, continuous hypoxia resulted in complete rescue of RGC somas and axons at this time point, with normal axonal myelination observed on electron microscopy. Though only partial, hypoxia-mediated rescue of complex I-deficient RGC somas and axons remained significant at P90. Hypoxia prevented reactive gliosis at P60, but the retinal accumulation of Iba1+ mononuclear phagocytic cells was not substantially reduced. Continuous hypoxia achieved dramatic rescue of early RGC degeneration in mice with severe mitochondrial dysfunction. Although complete rescue was not durable to P90, our observations suggest that investigating the mechanisms underlying hypoxia-mediated neuroprotection of RGCs may identify useful therapeutic strategies for optic neuropathies resulting from less profound mitochondrial impairment, such as Leber hereditary optic neuropathy.

Development of cardioprotective effect of chronic continuous hypoxia in rats with induced metabolic syndrome

Background. It is known that adaptation to chronic continuous hypoxia leads to a pronounced cardioprotective effect. The efficiency of acute adaptation to hypoxia is reduced in metabolic syndrome. However, the effectiveness of the myocardial infarct size-limiting effect of chronic continuous hypoxia in metabolic syndrome remains an understudied fact. The aim. To study the effectiveness of the development of the myocardial infarct size-limiting effect of chronic continuous hypoxia in rats with metabolic syndrome. Materials and methods. The study was carried out on 43 Wistar rats. Adaptation of animals to chronic hypoxia was performed during 21 days in a hypoxic chamber (12 % O2, 0.3 % CO2). Metabolic syndrome was modeled by keeping rats on a high-carbohydrate and high-fat diet (proteins 16 %, fats 21 %, carbohydrates 46 % (including fructose 17 %), cholesterol 0.125 %, cholic acid 0.5 %) for 12 weeks with replacement of drinking water with 20% fructose solution. Coronary occlusion-reperfusion was performed in vivo. The effect of chronic hypoxia and metabolic syndrome on myocardial infarct size was assessed. Results. It was found that myocardial infarct size in rats after chronic continuous hypoxia was 38 % less than in animals of the control group. In rats which were kept on a high-carbohydrate and high-fat diet we observed the obesity, decreased glucose tolerance, increased serum triglycerides level, and hypertension. Adaptation to chronic continuous hypoxia in animals on a high-carbohydrate and high-fat diet improved carbohydrate metabolism, but did not affect the severity of other metabolic disorders. At the same time, the myocardial infarct size-limiting effect of chronic hypoxia was not observed in rats with metabolic syndrome. Conclusion. Metabolic syndrome eliminated myocardial infarct size-limiting effect of chronic continuous hypoxia.

Causes of continuous and short-term hypoxia in rivers entering the sea: a case of Minjiang River in Fujian Province

Abstract In the last 10 years, the Minjiang River, which is the longest river in the Fujian Province in Southeast China, has been facing a downward trend of dissolved oxygen (DO) and a frequent occurrence of hypoxia. In this study, the development of the continuous and short-term presence of low DO was investigated by using the water age concept and average DO consumption concept based on a three-dimensional Environmental Fluid Dynamics Code in the Minjiang River. The results revealed that the spatial distribution of DO was affected by temperature, runoff, pollution emission, tidal advection, and hypoxic water discharge from the reservoir bottom. The continuous low DO in the water of the North Channel occurred frequently when the enough pollutants were aerobically decomposed faster than the rate of oxygen reaeration during the high temperature and low river discharge period. In addition, the water age and reaeration time decreased with a rapid increase in the water flow from the Shuikou dam when the reservoir capacity was released via drainage. The results of this study provide scientific insights on the mechanism involved in the occurrence of hypoxia and suggest countermeasures for addressing hypoxic problems in estuaries.

Differential hypoxia tolerance of eastern oysters from the northern Gulf of Mexico at elevated temperature

Increasing prevalence of hypoxia in shallow waters of U.S. Gulf of Mexico (GoM) estuaries can pose a serious threat to eastern oysters (Crassostrea virginica). Their tolerance to hypoxia, however, is not well characterized, especially at elevated temperatures (>30 °C) typical of GoM estuaries in summer. Moreover, it is unknown whether differences in hypoxia tolerance exist between GoM oyster populations growing in estuaries differing in local environmental conditions. Wild oyster broodstocks were collected from four estuarine sites in Texas (Packery Channel, PC and Aransas Bay, AB) and Louisiana (Calcasieu Lake, CL and Vermilion Bay, VB) and their adult progenies (F1) were tested (Study 1) under continuous hypoxia (<2.0 mg O2 L−1) at 32 °C. Significant differences in hypoxia tolerance were found between F1 populations with calculated median lethal time (LT50) ranging from 3.9 to 12.5 days. PC and CL oysters were the most and least tolerant populations, respectively. The study was repeated twice more (Studies 2 and 3) using PC and CL oysters, and their responses at the organismic, cellular, and biochemical levels were investigated. Valve movement was monitored, and oysters were sampled to measure hemocyte density, plasma protein, calcium and glutathione concentrations, and digestive gland alanine and succinate concentrations after either 3–5 days (Study 2) or 1–3 days (Study 3) of hypoxia exposure. From the onset of hypoxia until their death, oysters stayed opened 13–32% of the time compared to 53–64% under normoxia, but no differences between populations were detected under hypoxia. PC oyster but not CL oyster plasma glutathione concentrations increased significantly in both studies. Under longer (3–5 days) hypoxia exposure, plasma calcium and glutathione concentrations of PC oysters were significantly higher than CL oysters. These results suggest PC oysters were better able to protect tissues against acidosis and oxidative damage during hypoxia and high temperature stress than CL oysters. Overall, our results indicate that oyster populations originating from the GoM vary in their response to hypoxia and high temperature stress and possess differential tolerance.