Periods Of Hypoxia Research Articles

Hypoxia-driven Hif2a coordinates mouse liver regeneration by coupling parenchymal growth to vascular expansion.

Oxygen is a key regulator of liver regeneration. Hypoxia-inherent to the expansion of parenchyme-activates Hif2a to couple hepatocyte mitosis with the angiogenic phase. Hif2a acts as a safeguard to initiate sinusoidal reconstruction only upon successful hepatocyte mitosis, thereby enforcing a timely order onto cell type-specific regeneration patterns. These findings portray the hypoxia-driven Hif2a-Vegf axis as a prime node in coordinating sinusoidal endothelial cell-hepatocyte crosstalk during liver regeneration. (Hepatology 2016;64:2198-2209).

Low Oxygen Levels Slow Embryonic Development of Limulus polyphemus.

The American horseshoe crab Limulus polyphemus typically spawns in the upper intertidal zone, where the developing embryos are exposed to large variations in abiotic factors such as temperature, humidity, salinity, and oxygen, which affect the rate of development. It has been shown that embryonic development is slowed at both high and low salinities and temperatures, and that late embryos close to hatching tolerate periodic hypoxia. In this study we investigated the influence of hypoxia on both early and late embryonic development in L. polyphemus under controlled laboratory conditions. Embryos were exposed to four different oxygen levels and their developmental stage was scored every second day. Embryos developed more slowly at both 5% O2 and 10% O2 than at the 21% O2 treatment; late development was arrested when oxygen was reduced to 2%. Our study confims that L. polyphemus not only tolerates pronounced hypoxia in later embryonic developmental stages, but also in earlier, previously unexplored, developmental stages.

Unusual Diversity of Myoglobin Genes in the Lungfish.

Myoglobin is a respiratory protein that serves as a model system in a variety of biological fields. Its main function is to deliver and store O2 in the heart and skeletal muscles, but myoglobin is also instrumental in homeostasis of nitric oxide (NO) and detoxification of reactive oxygen species (ROS). Almost every vertebrate harbors a single myoglobin gene; only some cyprinid fishes have two recently duplicated myoglobin genes. Here we show that the West African lungfish Protopterus annectens has at least seven distinct myoglobin genes (PanMb1-7), which diverged early in the evolution of lungfish and showed an enhanced evolutionary rate. These myoglobins are lungfish specific, and no other globin gene was found amplified. The myoglobins are differentially expressed in various lungfish tissues, and the brain is the main site of myoglobin expression. The typical myoglobin-containing tissues, the skeletal muscle and the heart, have much lower myoglobin mRNA levels. Muscle and heart express distinct myoglobins (PanMb1 and PanMb3, respectively). In cell culture, lungfish myoglobins improved cellular survival under hypoxia albeit with different efficiencies and reduced the production of reactive oxygen species. Only Mb2 and Mb6 enhanced the energy status of the cells. The unexpected diversity of myoglobin hints to a functional diversification of this gene: some myoglobins may have adapted to the O2 requirements of the specific tissue and help the lungfish to survive hypoxic periods; other myoglobins may have taken over the roles of neuroglobin and cytoglobin, which appear to be missing in the West African lungfish.

Aerobic scope and oxygen regulation of New Zealand geoduck (Panopea zelandica) in response to progressive hypoxia

Recent efforts to cultivate subtidal New Zealand geoducks (Panopea zelandica Quoy and Gaimard, 1835) in intertidal areas have been challenged due to daily hypoxia. Hence, further understanding of physiological responses of geoducks of different sizes under different oxygen partial pressures (PO2) is required to optimize their husbandry. Without this knowledge, the risk of increasing cultivation costs due to growth depression and mortality may increase in both magnitude and frequency. Hence, this study investigated the respiration, aerobic scope, critical oxygen partial pressure (PcO2), and oxygen regulation capacity from normoxia to hypoxia in two size classes of fed and starved P. zelandica. The PcO2 was determined to be ~4kPa for all geoduck groups. The respiration rates of fed small geoducks decreased significantly from normoxia (16.7–~21kPa) to mild hypoxia (PcO2–16.7kPa). Conversely, the respiration rates of starved geoducks from both size classes, and large fed geoducks were maintained at a constant level when exposed to the same change in oxygen concentration. However, all geoducks experienced decreased respiration rates during severe hypoxia (0kPa–PcO2). In addition, overall oxyregulatory capacity, assessed using a regulation index, was affected by size rather than by nutritional stress. Large geoducks maintain oxygen consumption across an oxygen gradient more effectively than small geoducks. Also, the aerobic scope of small geoducks decreased significantly with declining PO2, while large geoducks maintained their aerobic scope under hypoxia. Hence, to avoid stress and maximize growth potential of cultivated geoducks, smaller individuals should be grown in areas that remain normoxic, whereas larger individuals may be transferred to on-growing sites that experience periodic hypoxia, potentially including tidal emersion. Statement of relevanceThe New Zealand geoduck clam (Panopea zelandica) has been identified as an emerging aquaculture species. However, efforts to cultivate geoducks intertidally have been challenged due to daily hypoxia. Hence, this study reports on physiological responses (respiration, aerobic scope, critical oxygen partial pressure, and oxygen regulation capacity) of geoducks of different sizes under different oxygen partial pressures to optimize their husbandry.

Effect of hemic hypoxia on dynamics of GFAP concentrations in the structures of the brain and blood serum of rats

This article clarifies the questions on study of hypoxic influence on distribution of filament and soluble forms of GFAP in various structures of the brain (neocortex, cerebellum, hippocampus, striatum, middle brain, pons) and blood of the rats. Quantitative analysis of the contents of GFAP in the brain structures of hypoxic rats has established that hemic hypoxia results in changes in intracellular levels of GFAP forms and also in updating their ratio, which allows one to assume not only a change in astroglial cells, but also testifies to reorganization in the system of intermediate filaments of astrocytes. The level of GFAP substantially changed in all cerebral formations, which was already investigated in the early terms of hypoxic period. Observations showed that hemic hypoxia exerted a varied influence on expression of neurospecific protein in the different structures of cerebrum of rats. Differences in expression of GFAP can be caused by the regional differences in astroglial cellular population, and also their internal features that define the possible answers to hypoxic damage in different functional and morphological structures of the brain. An increase in expression of the investigated form of protein can explain strengthening of astroglial reactivity, a feature of the brain that appears in various types of pathologies of the CNS. Reactive asters in such exhibit hypertrophy and are characterized by an increased level of GFAP, which is an early and reliable indicator of astroglial pathology. An increase in expression of the investigated form of protein may be explained by strengthening of astroglial reactivity, a feature of the brain that appears in various types of pathologies of the CNS. The contents of GFAP in the blood of adult rats, as a result of the hypoxic influence received from it, can indicate a release of GFAP from damaged astrocytes in the blood flow.

Cause and prevention of demyelination in a model multiple sclerosis lesion.

ObjectiveDemyelination is a cardinal feature of multiple sclerosis, but it remains unclear why new lesions form, and whether they can be prevented. Neuropathological evidence suggests that demyelination can occur in the relative absence of lymphocytes, and with distinctive characteristics suggestive of a tissue energy deficit. The objective was to examine an experimental model of the early multiple sclerosis lesion and identify pathogenic mechanisms and opportunities for therapy.MethodsDemyelinating lesions were induced in the rat spinal dorsal column by microinjection of lipopolysaccharide, and examined immunohistochemically at different stages of development. The efficacy of treatment with inspired oxygen for 2 days following lesion induction was evaluated.ResultsDemyelinating lesions were not centered on the injection site, but rather formed 1 week later at the white–gray matter border, preferentially including the ventral dorsal column watershed. Lesion formation was preceded by a transient early period of hypoxia and increased production of superoxide and nitric oxide. Oligodendrocyte numbers decreased at the site shortly afterward, prior to demyelination. Lesions formed at a site of inherent susceptibility to hypoxia, as revealed by exposure of naive animals to a hypoxic environment. Notably, raising the inspired oxygen (80%, normobaric) during the hypoxic period significantly reduced or prevented the demyelination.InterpretationDemyelination characteristic of at least some early multiple sclerosis lesions can arise at a vascular watershed following activation of innate immune mechanisms that provoke hypoxia, and superoxide and nitric oxide formation, all of which can compromise cellular energy sufficiency. Demyelination can be reduced or eliminated by increasing inspired oxygen to alleviate the transient hypoxia. Ann Neurol 2016;79:591–604

Mécanismes de résistance à la castration : l’hypoxie intratumorale stimule l’expression du récepteur aux androgènes

Tumor hypoxia and its biological consequence lead to microenvironment adaptation of tumor initiation, promotion and progression. The aim of the study was to observe the influence of hypoxia on the expression of the androgen receptor (AR), using an original model of multicellular spheroids obtained from castration-resistant prostate tumor cells. Two human castration-resistant prostate cancer cell lines have been used to generate multicellular tumor spheroids (MTS). The conditions and duration of incubation modulated the final size of the MTS and the intrinsic hypoxia gradient. The expression of AR was studied by immunohistochemistry (IHC) and secretion of PSA measured in the culture medium. The IHC expression of AR was characterized by a decreasing gradient from the periphery to the center of MTS (less intense in central hypoxic zone), corresponding to a nuclear translocation of activated AR. This result was proportionally correlated with the duration of hypoxic incubation period. Hypoxia caused significant increase in AR expression at 6h of oxygen deprivation. This activation of AR was correlated with transcriptional activity increase of target genes, including increased secretion of PSA. This demonstration of activation, increased expression and increased transcriptional activity of AR by hypoxia is the first to have been made with an original model of hypoxia, closer to reality than previous models, i.e. close to tissue hypoxia observed in primary prostate cancer. 4.

The interplay between the surface and bottom water environment within the Benguela Upwelling System over the last 70 ka

AbstractThe Benguela Upwelling System (BUS), located between 30 and 20°S, is one of the fundamental high‐productivity systems of the world ocean. The BUS has previously been studied in terms of primary productivity and ecology over glacial‐interglacial timescales; however, the response and coupling with the benthic environment have received little attention. Here, for the first time, we present a high‐resolution reconstruction of the BUS highlighting the link between surface and benthic productivity and their response to climatic and oceanographic changes over the last 70 ka. The study is based on benthic foraminiferal faunal analysis together with analyses of diatom assemblages, grain size of the terrigenous fraction, and stable O and C isotopic and bulk biogenic components of core GeoB3606‐1. We reveal significant shifts in benthic foraminiferal assemblage composition. Tight coupling existed between the surface and bottom water environment especially throughout marine isotope stages 4 and 3 (MIS4 and MIS3). Due to the high export production, the site has essentially experienced continuous low oxygen conditions; however, there are time periods where the hypoxic conditions were even more notable. Two of these severe hypoxic periods were during parts of MIS4 and MIS3 where we find an inverse relationship between diatom and benthic foraminifera accumulation, meaning that during times of extremely high phytodetritus export we note strongly suppressed benthic productivity. We also stress the importance of food source for the benthos throughout the record. Shifts in export productivity are attributed not only to upwelling intensity and filament front position, but also, regional‐global climatic and oceanographic changes had significant impact on the BUS dynamics.

MR Imaging–derived Oxygen-Hemoglobin Dissociation Curves and Fetal-Placental Oxygen-Hemoglobin Affinities

Purpose To generate magnetic resonance (MR) imaging-derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level-dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. Materials and Methods All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%-10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%-100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of three-dimensional gradient-echo T2*- and T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2* values were derived for each tissue. MR imaging-based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2*divided by R2*at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2* divided by R2*at baseline scaled (y) equals 0.5. Results The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P < .0001]). The placenta showed a reduction of 18% ± 4 in mean apparent P50 values from day 14.5 to day 17.5 (P = .003). Reproduction of the MR imaging-based oxygen-hemoglobin dissociation curves with a shorter protocol that excluded the hypoxic periods was demonstrated. Conclusion MR imaging-based oxygen-hemoglobin dissociation curves and oxygen-hemoglobin affinity information were derived for pregnant mice by using 9.4-T MR imaging, which suggests a potential to overcome the need for direct sampling of fetal or maternal blood. Online supplemental material is available for this article.

Eukaryotic translation initiation factor 5A (eIF5A) is essential for HIF-1α activation in hypoxia

The eukaryotic initiation factor 5A (eIF5A) is an essential protein involved in translation elongation and cell proliferation. eIF5A undergoes several post-translational modifications including hypusination and acetylation. Hypusination is indispensable for the function of eIF5A. On the other hand, the precise function of acetylation remains unknown, but it may render the protein inactive since hypusination blocks acetylation. Here, we report that acetylation of eIF5A increases under hypoxia. During extended hypoxic periods an increase in the level of eIF5A acetylation correlated with a decrease in HIF-1α, suggesting involvement of eIF5A activity in HIF-1α expression under hypoxia. Indeed, suppression of eIF5A by siRNA oligo-mediated knockdown or treatment with GC7, a deoxyhypusine synthase inhibitor, led to significant reduction of HIF-1α activity. Furthermore, knockdown of eIF5A or GC7 treatment reduced tumor spheroid formation with a concomitant decrease in HIF-1α expression. Our results suggest that functional, hypusinated eIF5A is necessary for HIF-1α expression during hypoxia and that eIF5A is an attractive target for cancer therapy.

Cell-Assisted Skin Grafting: Improving Texture and Elasticity of Skin Grafts through Autologous Cell Transplantation.

Full-thickness skin grafts are widely used in plastic and reconstructive surgery. Their poor textural durability and associated contracture make them less desirable than skin flaps. Currently, stromal vascular fraction cells hold great promise because of their angiogenic potential, which may ameliorate the hypoxic period after skin grafting. In this study, autologous transplantation of stromal vascular fraction cells was used in combination with skin grafts to determine whether it improved the texture and other physical property of skin grafts. Stromal vascular fraction cells were isolated and injected under full-thickness skin grafts in a cohort of 20 rats; a second cohort of 20 rats served as controls. Skin grafts were harvested and analyzed on days 14, 30, and 90 after injections. Bioluminescent imaging with luciferase-stromal vascular fraction cells was used for cell tracing. Contracture ratios, elasticity modulus, and the stiffness of each graft were evaluated. Angiogenesis was evaluated using immunohistochemical techniques against vascular endothelial growth factor. Blood flow signals of the graft were also measured, and expression of vascular endothelial growth factor, hepatocyte growth factor, and basic fibroblast growth factor was assessed in all grafts. Stromal vascular fraction cells markedly decreased the contracture of skin grafts and improved their resilience and elasticity after 1 month. Histologically, the cells enhanced skin thickness and skin vascularization. Moreover, expression of vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor also increased in the stromal vascular fraction group. Autologous stromal vascular fraction cell transplantation enhances angiogenesis after skin grafting and improves the texture and elasticity of skin grafts.

Early tranexamic acid administration: A protective effect on gut barrier function following ischemia/reperfusion injury.

The mucus barrier is a critical component of the gut barrier and may be disrupted by pancreatic enzymes following trauma/hemorrhagic shock (T/HS). Luminal strategies against pancreatic enzyme activation or contact with the intestine are protective of the mucus layer and gut barrier integrity following T/HS. There is increasing evidence the use of tranexamic acid (TA) attenuates inflammatory responses in cardiac surgery and is readily absorbed from the gut. We therefore postulated that systemic administration of TA would attenuate mucus degradation and gut barrier failure following T/HS. This was studied in an in vitro model. Confluent monolayers of HT29-MTX (mucus-producing clone) and Caco-2 cocultures were exposed to 90 minutes of hypoxia followed by reoxygenation (H/R), luminal trypsin (5 μM), or both treatment groups. In a subset of experiments, TA (40 μM or 150 μM) was added to the basal chamber (systemic side) of intestinal cell cultures immediately following the hypoxic period. Mucus barrier function was indexed by rheologic measurement of both mucus thickness and viscosity (G', dyne/cm) and oxidant stress. Intestinal cell barrier integrity was indexed by transepithelial electrical resistance, permeability to fluorescein isothiocyanate-dextran, and apoptosis by flow cytometry. Exposure to both trypsin and H/R of Caco-2/HT29-MTX cocultures led to the most severe effect on mucus barrier function. Administration of TA immediately following hypoxia abrogated the effects noted on mucus barrier function. The epithelial barrier was also most severely impacted by both trypsin and H/R. Addition of TA after the hypoxic event was shown to be protective. Intestinal mucus physiochemical properties and intestinal barrier function were most severely impacted by exposure to both trypsin (concentration related) and H/R. The "systemic" administration of TA immediately after the hypoxic period was protective and suggests an additional role for early administration of TA in trauma patients in shock.

Genetic and Pharmacological Modulation of Akt1 for Improving Ovarian Graft Revascularization in a Mouse Model.

Ovarian tissue cryopreservation and transplantation is one of a few available treatments for fertility preservation in women diagnosed with cancer. Rapid revascularization is essential for reducing hypoxic damage after grafting and protecting the primordial follicles reserve. Using a mouse model of heterotopic ovarian graft transplantation, we have delineated the role of endothelial Akt1 expression using longitudinal magnetic resonance imaging follow-up to quantify angiogenic response. Endothelial Akt1 activation in ovarian grafts promoted angiogenesis to support the graft during posttransplantation hypoxic period. Similarly, simvastatin therapy activated Akt1 at the transplantation site and improved the revascularization and vascular support of ovarian grafts. These results serve as an important first step toward pharmacological intervention to improve revascularization of ovarian grafts and restoration of fertility in cancer survivors. The pro-angiogenic effects reported here may extend beyond improving ovarian graft reception in fertility preservation and could potentially be used for different organ or tissue transplantation.

Early adenosine release contributes to hypoxia-induced disruption of stimulus-induced sharp wave-ripple complexes in rat hippocampal area CA3.

We investigated the effects of hypoxia on sharp wave-ripple complex (SPW-R) activity and recurrent epileptiform discharges in rat hippocampal slices, and the mechanisms underlying block of this activity. Oxygen levels were measured using Clark-style oxygen sensor microelectrodes. In contrast to recurrent epileptiform discharges, oxygen consumption was negligible during SPW-R activity. These network activities were reversibly blocked when oxygen levels were reduced to 20% or less for 3min. The prolongation of hypoxic periods to 6min caused reversible block of SPW-Rs during 20% oxygen and irreversible block when 0% oxygen (anoxia) was applied. In contrast, recurrent epileptiform discharges were more resistant to prolonged anoxia and almost fully recovered after 6min of anoxia. SPW-Rs were unaffected by the application of 1-butyl-3-(4-methylphenylsulfonyl) urea, a blocker of KATP channels, but they were blocked by activation of adenosine A1 receptors. In support of a modulatory function of adenosine, the amplitude and incidence of SPW-Rs were increased during application of the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Interestingly, hypoxia decreased the frequency of miniature excitatory post-synaptic currents in CA3 pyramidal cells, an effect that was converted into increased frequency by the adenosine A1 agonist DPCPX. In addition, DPCPX also delayed the onset of hypoxia-mediated block of SPW-Rs. Our data suggest that early adenosine release during hypoxia induces a decrease in pre-synaptic glutamate release and that both might contribute to transient block of SPW-Rs during hypoxia/anoxia in area CA3.

Responses of Coastal Largemouth Bass to Episodic Hypoxia

AbstractThe river systems inhabited by coastal populations of Largemouth Bass Micropterus salmoides in North Carolina and along the Atlantic and Gulf coast regions exhibit episodic (i.e., several times per year) fluctuations in environmental conditions (e.g., dissolved oxygen [DO]). Laboratory studies have documented the effects of low DO (hypoxia) on Largemouth Bass, yet few field studies have examined these effects in open systems. The objective of this study was to determine the effects of episodic hypoxia on Largemouth Bass distribution, survival, and feeding success in an open coastal system. We collected 45 Largemouth Bass from four tributaries of the Chowan River and tagged them with acoustic transmitters. Fish movements were monitored using active tracking and passive receivers, and these data were compared with DO levels recorded in the tributaries and main‐stem Chowan River. We found that tagged Largemouth Bass exhibited avoidance behavior at DO concentrations below 1.8 mg/L, with some seeking higher DO in the main stem or near tributary mouths during hypoxic events in the tributaries. The natural mortality rate of Largemouth Bass was low compared with rates reported in other studies, indicating that Largemouth Bass in coastal systems are able to survive hypoxic events. Analysis of stomach contents collected during hypoxic and non‐hypoxic periods indicated that Largemouth Bass had less food in their stomachs under hypoxic conditions; however, the CPUE (fish/h of pedal time) of potential prey fishes was not lower during hypoxic periods relative to non‐hypoxic periods, and thus a change in foraging opportunities did not appear to drive Largemouth Bass movement.

Hypoxic Preconditioning Mitigates Diaphragmatic Skeletal Muscle Fatigue during Reoxygenation via ROS and ERK Signaling

Reoxygenation of skeletal muscle after hypoxia has been shown to induce tissue damage and lead to muscle dysfunction. For instance, oxygen levels are depleted during periods of intense exercise and the subsequent flow of oxygenated blood can induce oxidative stress. However, the mechanism for reoxygenation-induced fatigue or injury in skeletal muscle has not been fully elucidated. In addition, limited research has focused on the potential of hypoxic preconditioning (HPC; alternating periods of hypoxia and normoxia) as an effective method for reducing muscle fatigue during reoxygenation. PURPOSE: This study investigated the hypothesis that HPC protects diaphragmatic muscle function during reoxygenation through ROS and ERK signaling. METHODS: Isolated mouse diaphragm muscle strips were either non-treated (n = 10), treated with HPC (n = 7), or exposed to a combination of the antioxidants Tiron and N-acetyl cysteine (NAC) (1mM each, n = 4) or an ERK inhibitor (PD98059, 100 μM, n = 5) prior to HPC treatment followed by a 30 min hypoxic period (PO2 = 5 Torr) and subsequent reoxygenation. The muscle strips were electrically stimulated in a myograph device containing Ringer’s solution during reoxygenation. Data were analyzed using a multi-way ANOVA, and expressed as means ± SE. P < 0.05 was the criterion level for significance. RESULTS: Our results demonstrated that HPC significantly increases muscle function during reoxygenation (37.7 ± 8.5% for treated vs. 9.8 ± 2.5% for control, P < 0.05; expressed as percent of the maximal force at the end of the contraction protocol). Inhibition of ROS signaling (5.22 ± 0.2% for treated vs. 9.8 ± 2.5% for control) and ERK activation (13.4 ± 4.4% for treated vs. 9.8 ± 2.5% for control) abolished the protective HPC effect on the muscle force development. CONCLUSION: We propose that HPC may reduce diaphragmatic skeletal muscle fatigue during reoxygenation through ROS signaling and the activation of the ERK pathway.

Oxygen limitations on marine animal distributions and the collapse of epibenthic community structure during shoaling hypoxia.

Deoxygenation in the global ocean is predicted to induce ecosystem-wide changes. Analysis of multidecadal oxygen time-series projects the northeast Pacific to be a current and future hot spot of oxygen loss. However, the response of marine communities to deoxygenation is unresolved due to the lack of applicable data on component species. We repeated the same benthic transect (n = 10, between 45 and 190 m depths) over 8 years in a seasonally hypoxic fjord using remotely operated vehicles equipped with oxygen sensors to establish the lower oxygen levels at which 26 common epibenthic species can occur in the wild. By timing our surveys to shoaling hypoxia events, we show that fish and crustacean populations persist even in severe hypoxia (<0.5 mL L(-1) ) with no mortality effects but that migration of mobile species occurs. Consequently, the immediate response to hypoxia expansion is the collapse of community structure; normally partitioned distributions of resident species coalesced and localized densities increased. After oxygen renewal and formation of steep oxygen gradients, former ranges re-established. High frequency data from the nearby VENUS subsea observatory show the average oxygen level at our site declined by ~0.05 mL L(-1) year(-1) over the period of our study. The increased annual duration of the hypoxic (<1.4 mL L(-1) ) and severely hypoxic periods appears to reflect the oxygen dynamics demonstrated in offshore source waters and the adjacent Strait of Georgia. Should the current trajectory of oxygen loss continue, community homogenization and reduced suitable habitat may become the dominant state of epibenthic systems in the northeast Pacific. In situ oxygen occurrences were not congruent with lethal and sublethal hypoxia thresholds calculated across the literature for major taxonomic groups indicating that research biases toward laboratory studies on Atlantic species are not globally applicable. Region-specific hypoxia thresholds are necessary to predict future impacts of deoxygenation on marine biodiversity.

Contribution of Nutrient and Organic Matter Sources to the Development of Periodic Hypoxia in a Tributary Estuary

The seasonal formation of periodic hypoxia within tributary estuaries is influenced by multiple nutrient and organic matter sources, both autochthonous and allochthonous. In contrast to lakes and flowing rivers, allochthonous inputs to estuaries include those from near-field sources in the watershed as well as far-field sources from adjacent marine systems that contribute nutrients, organic matter, and hypoxic water via estuarine circulation. This study utilized a reduced-complexity eutrophication model to quantify the contribution of individual sources to hypoxia in the York River estuary (YRE), and assess the reductions necessary to mitigate hypoxic conditions. Results indicate that portions of the oligohaline YRE are influenced by organic loading from the watershed, while the lower mesohaline region is influenced by both internal phytoplankton production and watershed loads. In the high mesohaline, watershed organic matter and internal phytoplankton production play an equally important role during the spring; however, in summer and fall oxygen concentrations appear to respond strongly to dissolved organic carbon (DOC) entering via advection from Chesapeake Bay (CB). The polyhaline region, which is frequently the site of reoccurring hypoxia, responded primarily to advected DOC from CB. Results indicate that different regions of the YRE may require different management strategies, and highlight the strong relationship between periodic hypoxia in the lower YRE and advection of labile organic matter from CB, a far-field input that requires a regional management approach. A cross-system comparison of nutrient budgets indicates that far-field sources can comprise a large portion of total system inputs in numerous tributary estuaries.

Heart rate and blood pressure responses during hypoxic cycles of a 3-week intermittent hypoxia breathing program in patients at risk for or with mild COPD.

The aim of this study was to provide information on heart rate and blood pressure responses during a 3-week intermittent hypoxia breathing program in COPD patients. Sixteen participants with COPD symptoms were randomly assigned to a hypoxia or control group and completed a 3-week intermittent hypoxia breathing program (five sessions per week, each consisting of three to five breathing cycles, each cycle lasting 3–5 minutes with 3-minute breaks between cycles). During the breathing cycles, the hypoxia group received hypoxic air (inspired fraction of oxygen 15%–12%), whereas the control group received normal air (sham hypoxia). During the breaks, all participants breathed normoxic room air. Arterial oxygen saturation, systolic and diastolic blood pressure, and heart rate were measured during the normoxic and hypoxic/sham hypoxic periods. For each breathing cycle, changes from normoxia to hypoxia/sham hypoxia were calculated, and changes were averaged for each of the 15 sessions and for each week. Changes in arterial oxygen saturation were significantly different between groups in the course of the 3 weeks (two-way analysis of variance for repeated measures), with post hoc differences in weeks 1, 2, and 3. During the course of the intermittent hypoxia application, no between-group differences were detected for blood pressure or rate pressure product values. Changes in heart rate were significantly different between groups in the course of the 3 weeks (two-way analysis of variance for repeated measures), with post hoc differences only in week 3. Averages over all 15 sessions were significantly higher in the hypoxia group for heart rate and rate pressure product, and tended to be increased for systolic blood pressure. The applied intermittent hypoxia breathing program resulted in specific and moderate heart rate and blood pressure responses, and did not provoke a progressive increase in blood pressure during the hypoxic cycles in the course of the application.

Interstitial lactate, lactate/pyruvate and glucose in rat muscle before, during and in the recovery from global hypoxia.

BackgroundHypoxia results in an imbalance between oxygen supply and oxygen consumption. This study utilized microdialysis to monitor changes in the energy-related metabolites lactate, pyruvate and glucose in rat muscle before, during and after 30 minutes of transient global hypoxia. Hypoxia was induced in anaesthetised rats by reducing inspired oxygen to 6% O2 in nitrogen.ResultsBasal values for lactate, the lactate/pyruvate ratio and glucose were 0.72 ± 0.04 mmol/l, 10.03 ± 1.16 and 3.55 ± 0.19 mmol/l (n = 10), respectively. Significant increases in lactate and the lactate/pyruvate ratio were found in the muscle after the induction of hypoxia. Maximum values of 2.26 ± 0.37 mmol/l for lactate were reached during early reperfusion, while the lactate/pyruvate ratio reached maximum values of 35.84 ± 7.81 at the end of hypoxia. Following recovery to ventilation with air, extracellular lactate levels and the lactate/pyruvate ratio returned to control levels within 30–40 minutes. Extracellular glucose levels showed no significant difference between hypoxia and control experiments.ConclusionsIn our study, the complete post-hypoxic recovery of metabolite levels suggests that metabolic enzymes of the skeletal muscle and their related cellular components may be able to tolerate severe hypoxic periods without prolonged damage. The consumption of glucose in the muscle in relation to its delivery seems to be unaffected.