Duration Of Hypoxia Research Articles

Reduced circulating growth hormone and insulin-like growth factor-1 and delayed growth of premature rats are aggravated by longer daily duration of chronic intermittent hypoxia exposure.

This study mainly aimed to investigate the effect of daily duration of chronic intermittent hypoxia (CIH) exposure on circulating growth hormone (GH)/insulin-like growth factor-1 (IGF-1) concentrations and body weight changes of premature rats. 40 healthy male SD rats aged six weeks were enrolled in this study. These rats were randomly divided into four groups (n = 10 per group), including normal control (NC) group (normal oxygen exposure every day), CIH-1 group (daily CIH exposure for 2 h), CIH-2 group (daily CIH exposure for 4 h), and CIH-3 group (daily CIH exposure for 8 h). The serum GH/IGF-1 concentrations and body weights in all rats were determined after 30 days of normal oxygen or CIH exposure. No significant difference was found with respect to the baseline body weight among the four groups of rats. After establishments of animal models with a duration of 30 days, significant differences were found respect to body weight, body weight changes, and serum GH/IGF-1 concentrations among the four groups of rats with a same trend (all P < 0.05): the highest values were all in NC group rats, followed CIH-1 group, CIH-2 group, and CIH-3 group rats. Among all the rats, the body weight changes correlated significantly with both serum GH and IGF-1 concentrations (both P < 0.05). CIH decreases circulating GH/IGF-1 concentrations and causes growth delay in premature rats. Such effects could be aggravated by increased daily duration of CIH exposures.

The Impact of Heterogeneous Cell Density in Hypoxic Tumors Treated with Radiotherapy.

Hypoxia is frequently found in solid tumors and is known to increase the resistance to several kinds of treatment modalities including radiation therapy. Besides, the treatment response is also largely determined by the total number of clonogenic cells, i.e., cells with unlimited proliferative capacity. Depending on the duration of hypoxia, the rate of proliferation and hence also the clonogen density could be expected to differ in hypoxic compartments. The combination at the microscale between heterogeneous tumor oxygenation and clonogen density could therefore be crucial with respect to the outcome of a radiotherapy treatment. In this study it was investigated the impact of heterogeneous clonogen density on the outcome of stereotactic radiotherapy treatments of hypoxic tumors. A recently developed three-dimensional model for tissue vasculature and oxygenation was used to create realistic in silico tumors with heterogeneous oxygenation. Stereotactic radiotherapy treatments were simulated, and cell survival was calculated on a voxel-level accounting for the oxygenation. For a tumor with a diameter of 1 cm and a baseline clonogenic density of 107/cm3 for the normoxic subvolume, when the relative density for the hypoxic cells drops by a factor of 10 the tumor control probability (TCP) decreases by about 10% when relatively small hypoxic volumes and few fractions are considered; longer treatments tend to level out the results. With increasing size of the hypoxic subvolume, the TCP decreased overall as expected, and the difference in TCP between a homogeneous and a heterogeneous distribution of cells increased. The results demonstrate a delicate interplay between the heterogeneous distribution of tumor oxygenation and clonogenic cells that could significantly impact on the treatment outcome of radiotherapy.

Effects of Hypoxia on Coupled Carbon and Iron Cycling Differ Between Weekly and Multiannual Timescales in Two Freshwater Reservoirs

AbstractFreshwater lakes and reservoirs play a disproportionate role in the global organic carbon (OC) budget, as active sites for carbon processing and burial. Associations between OC and iron (Fe) are hypothesized to contribute substantially to the stabilization of OC in sediment, but the magnitude of freshwater Fe‐OC complexation remains unresolved. Moreover, global declines in bottom‐water oxygen concentrations have the potential to alter OC and Fe cycles in multiple ways, and the net effects of low‐oxygen (hypoxic) conditions on OC and Fe are poorly characterized. Here, we measured the pool of Fe‐bound OC (Fe‐OC) in surficial sediments from two eutrophic reservoirs, and we paired whole‐ecosystem experiments with sediment incubations to determine the effects of hypoxia on OC and Fe cycling over multiple timescales. Our experiments demonstrated that short periods (2–4 weeks) of hypoxia can increase aqueous Fe and OC concentrations while decreasing OC and Fe‐OC in surficial sediment by 30%. However, exposure to seasonal hypoxia over multiple years was associated with a 57% increase in sediment OC and no change in sediment Fe‐OC. These results suggest that the large sediment Fe‐OC pool (∼30% of sediment OC in both reservoirs) contains both oxygen‐sensitive and oxygen‐insensitive fractions, and over multiannual timescales OC respiration rates may play a more important role in determining the effect of hypoxia on sediment OC than Fe‐OC dissociation. Consequently, we anticipate that global declines in oxygen concentrations will alter OC and Fe cycling, with the direction and magnitude of effects dependent upon the duration of hypoxia.

Cerebral microangiopathy in men with obstructive sleep apnea syndrome

To determine factors associated with the development of small vessel disease (SVD) in patients with obstructive sleep apnea syndrome (OSA). One hundred and fifty-two patients with risk factors for the development of cerebrovascular diseases were examined. Based on the results of polysomnography, patients were divided into groups with- (n=84) and without (n=68) OSA. The groups were matched by age, prevalence of arterial hypertension and diabetes mellitus. SVD was diagnosed using brain MRI. Laboratory tests included an assessment of parameters of lipid metabolism, glucose metabolism, concentration of C-reactive protein (CRP), levels of homocysteine and creatinine with the calculation of glomerular filtration rate (GFR). Patients with OSA, compared with those without OSA, were characterized by a statistically significant number of gliosis foci, with their large sizes, more frequent changes on the Fazekas scales and the Hassan scale. The most severe degree of damage according to the Hassan scale in patients with OSA was detected more often (55 (66%) and 27 (39%) OR=2.89, 95% CI 1.47-5.67, p=0.002). More pronounced atrophic changes in the brain, an increase in the size of the III ventricle and the index of the anterior horns, significantly lower GFR and higher levels of CRP were noted in the OSA group. Patients with OSA and duration of nocturnal hypoxia for more than 2 minutes were more likely to have hyperintensity of subcortical regions. In patients with OSAS, pronounced manifestations of SMD were associated with a significantly higher level of morning systolic blood pressure (MAP): 140 [120; 150] vs. 127 [120; 130] p=0.029; increased levels of blood homocysteine: 14 [11; 17.8] vs. 13 [9.7; 12.5] p=0.049; a decrease in GFR: 79 [71; 87.3] vs. 89.8 [80.3; 94] p=0.002, respectively. OSA and intermittent nocturnal hypoxia are independent risk factors for SMD. A more severe micro-focal vascular lesion in OSA is associated with a decrease in renal filtration function, an increase in morning blood pressure and an elevation in homocysteine level.

Time Under 90% Oxygen Saturation and Systemic Hypertension in Patients with Obstructive Sleep Apnea Syndrome.

The diagnosis and severity of obstructive sleep apnea (OSA) are commonly based on the apnea hypopnea index (AHI). However, patients with similar severity AHIs may show widely varying comorbidities and risks for cardiovascular disease, which may be associated with different severities of nocturnal hypoxia. The percentage of cumulative time with oxygen saturation below 90% in total sleep time (T90) is receiving increasing attention in OSA research because it describes the duration and degree of hypoxia during the whole sleep. This study aimed to explore the distribution of T90 in OSA patients with similar severity and to evaluate the relationship between T90 and hypertension. A total of 775 patients with OSA were enrolled in this study, all participants were divided into groups according to the T90 value: light hypoxia (T90≤5%), mild hypoxia (T90 accounted for 5-10%), moderate hypoxia (T90 accounted for 10-25%), and severe hypoxia (T90>25%). Multivariate logistic regression analysis was performed to assess the association between T90 and hypertension. Of the patients with mild OSA, 94.33% had light hypoxia, and 88.64% of moderate OSA patients had light hypoxia. The proportions of light, mild, moderate, and severe hypoxia among patients with severe OSA were 28.60%, 17.69%, 21.40%, and 32.31%, respectively. After adjustment for potential confounders, the risk of hypertension in patients with severe OSA increased according to the severity categories of T90. The odds ratio for T90 accounting for 10-25% relative to T90≤5% was 2.544 (95%confidence interval, 1.254-5.164; P=0.010) and as high as 2.692 (95%confidence interval, 1.403-5.166; P=0.003) in patients with T90>25%. OSA patients with similar degree of AHI may have different T90 values, especially in severe OSA. A higher T90 was independently associated with the risk of hypertension after adjustment for traditional risk factors in patients with severe OSA. Our findings highlight the potential role for T90 in predicting hypertension in patients severe OSA.

A Tale of Two: When Neural Stem Cells Encounter Hypoxia.

Normoxia is defined as an oxygen concentration of 20.9%, as in room air, whereas hypoxia refers to any oxygen concentration less than this. Any physiological oxygen deficiency or tissue oxygen deficiency relative to demand is called hypoxia. Neural stem cells (NSCs) are multipotent stem cells that can differentiate into multiple cell lines such as neurons, oligodendrocytes, and astrocytes. Under hypoxic conditions, the apoptosis rate of NSCs increases remarkably in vitro or in vivo. However, some hypoxia promotes the proliferation and differentiation of NSCs. The difference is related to the oxygen concentration, the duration of hypoxia, the hypoxia tolerance threshold of the NSCs, and the tissue source of the NSCs. The main mechanism of hypoxia-induced proliferation and differentiation involves an increase in cyclin and erythropoietin concentrations, and hypoxia-inducible factors play a key role. Multiple molecular pathways are activated during hypoxia, including Notch, Wnt/β-catenin, PI3K/Akt, and altered microRNA expression. In addition, we review the protective effect of exogenous NSCs transplantation on ischemic or anoxic organs, the therapeutic potential of hypoxic preconditioning on exogenous NSCs and clinical application of NSCs.

Nasal high-flow therapy to Optimise Stability during Intubation: the NOSI pilot trial

ObjectiveIn adult patients with acute respiratory failure, nasal high-flow (NHF) therapy at the time of intubation can decrease the duration of hypoxia. The objective of this pilot study was to...

Hypoxic breathing produces more intense hypoxemia in elderly women than in elderly men.

Background: Brief hypoxic exposures are increasingly applied as interventions for aging-related conditions. To optimize the therapeutic impact of hypoxia, knowledge of the sex-related differences in physiological responses to hypoxia is essential. This study compared hypoxia-induced hypoxemic responses in elderly men and women. Methods: Seven elderly men (70.3 ± 6.0years old) and nine women (69.4 ± 5.5years old) breathed 10% O2 for 5min while arterial (SaO2; transcutaneous photoplethysmography) and cerebral tissue O2 saturation (ScO2; near-infrared spectroscopy), ventilatory frequency, tidal volume, minute-ventilation, and partial pressures of end-tidal O2 (PETO2) and CO2 (mass spectrometry) were continuously monitored. Cerebral tissue oxygen extraction fraction (OEF) equaled (SaO2-ScO2)/SaO2. Results: During 5min hypoxia SaO2 fell from 97.0 ± 0.8% to 80.6 ± 4.6% in the men and from 96.3 ± 1.4% to 72.6 ± 4.0% in the women. The slope ΔSaO2/min was steeper in the women than the men (-4.71 ± 0.96 vs. -3.24 ± 0.76%/min; p = 0.005). Although SaO2 fell twice as sharply per unit decrease in PETO2 in the women than the men (-1.13 ± 0.11 vs. -0.54 ± 0.06%/mmHg; p = 0.003), minute-ventilation per unit hypoxemia increased less appreciably in the women (-0.092 ± 0.014 vs. -0.160 ± 0.021L/min/%; p = 0.023). OEF fell with hypoxia duration in the women, but remained stable in the men. Conclusion: During 5min hypoxic breathing, elderly women experience more intense hypoxemia and reduced chemoreflex sensitivity vs. their male counterparts, which may lower OEF stability in women despite augmented O2 dissociation from hemoglobin during hypoxia. These sex-related differences merit attention when implementing brief hypoxic exposures for therapeutic purposes.

VOLUMETRIC CAPNOGRAPHY FOR RESPIRATORY MONITORING OF PATIENTS DURING ROUTINE COLONOSCOPY WITH ROOM-AIR AND CARBON DIOXIDE INSUFFLATION.

Capnography and carbon dioxide (CO2) insufflation during gastrointestinal endoscopy under sedation are associated with safety and comfort improvements, respectively. Capnography can provide early detection of apnea and hypoxemia, whereas CO2 insufflation causes lower periprocedural discomfort. This is the first study to report the application of volumetric capnography in colonoscopy. This study aimed to evaluate the use of volumetric capnography with room air (RA) and CO2 insufflation during routine colonoscopy. In this prospective cohort study, 101 patients who underwent routine colonoscopy under sedation with volumetric capnography monitoring were included. Insufflation with RA was used to distend the intestinal lumen in group 1 (n=51), while group 2 (n=50) used CO2 insufflation. The primary endpoints were episodes of hypoxia, alveolar hypoventilation, and end-tidal CO2 (EtCO2). The secondary endpoints were tidal volume per minute, consumption of sedation medications, and post-procedure pain using the Gloucester modified pain scale. The number of episodes of hypoxia (SpO2<90%) was similar between the groups: four episodes in Group 1 and two episodes in Group 2. The duration of hypoxia was significantly longer in group 2 (P=0.02). Hypoalveolar ventilation (EtCO2) occurred more frequently in Group 2 than in Group 1 (27 vs 18 episodes, P=0.05). Regarding EtCO2, Group 2 showed higher values in cecal evaluation (28.94±4.68 mmHg vs 26.65±6.12 mmHg, P=0.04). Regarding tidal volume per minute, Group 2 had significantly lower values at the cecal interval compared to Group 1 (2027.53±2818.89 vs 970.88±1840.25 L/min, P=0.009). No episodes of hypercapnia (EtCO2 > 60 mmHg) occurred during the study. There was no difference in the consumption of sedation medications between the groups. Immediately after colonoscopy, Group 2 reported significantly less pain than Group 1 (P=0.05). In our study, volumetric capnography during colonoscopy was feasible and effective for monitoring ventilatory parameters and detecting respiratory complications. CO2 insufflation was safe and associated with less pain immediately after colonoscopy.

Cerebral Hemodynamics and Regional Oxygen Metabolism during Ductus Arteriosus Ligation in Preterm Infants

Introduction: Neurodevelopmental impairment is a growing concern for preterm infants who received surgical ligation of patent ductus arteriosus (PDA). We aimed to explore the cerebral hemodynamics during the critical period of PDA ligation. Methods: Very-low-birth-weight (VLBW) preterm infants who underwent PDA ligation were prospectively enrolled. Patients were monitored preoperatively and until 72 h post-ligation. Middle cerebral artery (MCA) flow, regional cerebral oxygen saturation (rcSO₂), and cardiac output were measured through Doppler ultrasound, near-infrared spectroscopy, and electrical cardiometry, respectively. Using rcSO₂ <55% indicating cerebral hypoxia, the duration (% of time) and burden (cumulative negative quantity of rsSO₂ <55% × the period [minutes]) were estimated. An abnormal MCA was defined as an MCA flow of <10th percentile of flow velocity or >90th percentile of pulsatility or resistance index. Poor outcomes were defined as in-hospital death or neurologic disorders, either neuroimaging or functional abnormalities, upon discharge. Results: Thirty-two VLBW infants were examined, and 15 (46.9%) had poor outcomes. Infants with poor outcomes had significantly longer duration of cerebral hypoxia (5.4 [2.2–32.3] vs. 1.8 [0.4–5.6] %, p = 0.033) and worse hypoxic burden (2,118 [684–13,549] vs. 622 [88–1,669] %minutes, p = 0.027). In a linear mixed model, rcSO₂ was positively correlated with arterial saturation (β 0.860, 95% CI: 0.649–1.070) and negatively correlated with abnormal MCA flow (β −5.287, 95% CI: −8.238 to −2.335). Conclusion: Longer duration of cerebral hypoxia and worse hypoxic burden post-ligation was associated with an increased risk of in-hospital mortality or neurologic disorders upon discharge in VLBW preterm infants.

Exercise and hypoxia unmask pulmonary vascular disease and right ventricular dysfunction in a 10- to 12-week-old swine model of neonatal oxidative injury.

Prematurely born young adults who experienced neonatal oxidative injury (NOI) of the lungs have increased incidence of cardiovascular disease. Here, we investigated the long‐term effects of NOI on cardiopulmonary function in piglets at the age of 10–12 weeks. To induce NOI, term‐born piglets (1.81 ± 0.06 kg) were exposed to hypoxia (10–12% FiO2), within 2 days after birth, and maintained for 4 weeks or until symptoms of heart failure developed (range 16–28 days), while SHAM piglets were normoxia raised. Following recovery (>5 weeks), NOI piglets were surgically instrumented to measure haemodynamics during hypoxic challenge testing (HCT) and exercise with modulation of the nitric‐oxide system. During exercise, NOI piglets showed a normal increase in cardiac index, but an exaggerated increase in pulmonary artery pressure and a blunted increase in left atrial pressure – suggesting left atrial under‐filling – consistent with an elevated pulmonary vascular resistance (PVR), which correlated with the duration of hypoxia exposure. Moreover, hypoxia duration correlated inversely with stroke volume (SV) during exercise. Nitric oxide synthase inhibition and HCT resulted in an exaggerated increase in PVR, while the PVR reduction by phosphodiesterase‐5 inhibition was enhanced in NOI compared to SHAM piglets. Finally, within the NOI piglet group, prolonged duration of hypoxia was associated with a better maintenance of SV during HCT, likely due to the increase in RV mass. In conclusion, duration of neonatal hypoxia appears an important determinant of alterations in cardiopulmonary function that persist further into life. These changes encompass both pulmonary vascular and cardiac responses to hypoxia and exercise. Key points Children who suffered from neonatal oxidative injury, such as very preterm born infants, have increased risk of cardiopulmonary disease later in life.Risk stratification requires knowledge of the mechanistic underpinning and the time course of progression into cardiopulmonary disease.Exercise and hypoxic challenge testing showed that 10‐ to 12‐week‐old swine that previously experienced neonatal oxidative injury had increased pulmonary vascular resistance and nitric oxide dependency.Duration of neonatal oxidative injury was a determinant of structural and functional cardiopulmonary remodelling later in life.Remodelling of the right ventricle, as a result of prolonged neonatal oxidative injury, resulted in worse performance during exercise, but enabled better performance during the hypoxic challenge test.Increased nitric oxide dependency together with age‐ or comorbidity‐related endothelial dysfunction may contribute to predisposition to pulmonary hypertension later in life.

Intermittent Hypoxia and Atherosclerosis: From Molecular Mechanisms to the Therapeutic Treatment.

Intermittent hypoxia (IH) has a dual nature. On the one hand, chronic IH (CIH) is an important pathologic feature of obstructive sleep apnea (OSA) syndrome (OSAS), and many studies have confirmed that OSA-related CIH (OSA-CIH) has atherogenic effects involving complex and interacting mechanisms. Limited preventive and treatment methods are currently available for this condition. On the other hand, non-OSA-related IH has beneficial or detrimental effects on the body, depending on the degree, duration, and cyclic cycle of hypoxia. It includes two main states: intermittent hypoxia in a simulated plateau environment and intermittent hypoxia in a normobaric environment. In this paper, we compare the two types of IH and summarizes the pathologic mechanisms and research advances in the treatment of OSA-CIH-induced atherosclerosis (AS), to provide evidence for the systematic prevention and treatment of OSAS-related AS.

Clinical case control study analysis of vestibular function in patients with obstructive sleep apnea-hypopnea syndrome.

To investigate the effects of hypoxia degree and sleep duration on vestibular function in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients. We made further study of the low oxygen levels of OSAHS and hypoxic duration on the impact of vestibular function, and further studied the OSAHS the longest apnea time and Vestibular Evoked Myogenic Potential (VEMP) abnormal rate and the relationship between the vestibular function of canal paralysis (CP). A total of 87 OSAHS patients and 47 healthy individuals were enrolled in this study. There was no difference in gender, age and body mass index (BMI) values in matched experimental groups. Other diseases of other systems were excluded. All the participants completed sleepiness questionnaires (i.e., the Epworth sleepiness scale and the STOP-BANG questionnaire) and the Dizziness Handicap Inventory (DHI). Additionally, a caloric test, positional test, electrocochleogram, and VEMP test were administered to evaluate the vestibular function of all the participants. A polysomnography (PSG) was also performed. The current investigation generated the following three major findings: (I) there was a significant correlation between body mass index and canal paresis [CP; P=0.014, odds ratio (OR) =1.791, 95% confidence interval (CI): 1.125-2.851] and a significant positive correlation between the DHI score and VEMP results (P=0.0061, OR =3.667, 95% CI: 1.449-9.276); (II) the CP abnormality rate of the OSAHS group was significantly higher than that of the control group (P<0.05); (III) there was a significant correlation between the longest apnea duration and the DHI score (r=-0.191, P<0.05). The abnormality rate of the vestibular function of OSAHS patients is higher than that of healthy people. OSAHS intermittent hypoxia can affect vestibular function in the inner ear, and the longer the duration of prolonged hypoxia, the more serious the vestibular function damage.

Fetoplacental oxygen homeostasis in pregnancies with maternal diabetes mellitus and obesity.

Despite improvements in clinical management, pregnancies complicated by pre-existing diabetes mellitus, gestational diabetes mellitus or obesity carry substantial risks for parent and offspring. Some of the endocrine and metabolic changes in parent and fetus in diabetes mellitus and obesity lead to fetal oxygen deficit, mostly due to insulin-induced accelerated fetal metabolism. The human fetus deals with reduced oxygenation through a wide range of adaptive responses that act at various levels in the placenta as well as the fetus. These responses ensure adequate oxygen delivery to the fetus, increase the oxygen transport capacity of fetal blood and redistribute oxygen-rich blood to vital organs such as the brain and heart. The liver has a central role in adapting to reduced oxygenation by increasing its oxygen extraction and stimulating erythropoietin synthesis to increase haematocrit. The type of adaptive response depends on the onset and duration of hypoxia and the severity of the metabolic disturbance. In pregnancies characterized by diabetes mellitus or obesity, these adaptive systems come under additional strain owing to the increased maternal supply of glucose and resultant fetal hyperinsulinaemia, both of which stimulate oxidative metabolism. In the rare situation that the adaptive responses are overwhelmed, stillbirth can ensue.

Maternal and Fetal Outcome of Normal and Abnormal Cardiotocographic Findings at A Tertiary Hospital in Ghana

Background: Cardiotocography (CTG) provides important information about the interaction between fetal cerebral and cardiac activities which are both modified by hypoxia. The duration and severity of hypoxia and associated biochemical abnormalities allinfluence the manifestations of fetal heart rate abnormalities. Antenatal fetal heart rate monitoring with CTG has potential in preventing intrauterine fetal death.Aim: The aim of the study was to compare the maternal and fetal outcome of pregnancies with normal and abnormal antepartum CTG tracings.Methodology: This descriptive retrospective review compared 200 consecutive women with normal and 200 with abnormal CTG tracings. The study lasted six months and spanned a period of time from beginning of January to end of June 2011. Demographic, pregnancy and delivery outcome data were retrieved from participants' charts and simple descriptive analysis was performed. Means and their standard deviations of continuous variables were calculated and difference between group mean were compared using the student test. Categorical variables were summarized as proportions and the chi-square test used to test for difference between groups. A p-value &lt; 0.05 was considered statistically significant.Results: Women with normal and abnormal CTG tracings were comparable in their demographic characteristics. Abnormal CTG tracings were associated with higher rate of preterm delivery (38.8% vs 18.8%, p = 0.001), caesarean section (77.9% vs 47.0%, p = 0.001)low birth weight (25.5% vs 9.1%, p = 0.001) and NICU admissions (36.5% vs 17.6%, p = 0.001). There was no difference in Apgar score or stillbirth rate between the two groups. Pregnancies with abnormal tracing were delivered about a week earlier than those with normaltracing. (37.8±2.9 vrs 38.3±2.6, p=0.001). Longer interval between tracing and delivery was associated with stillbirth.Conclusion: Abnormal antepartum CTG tracing was associated with higher preterm delivery, caesarean section, low birth weight and NICU admission. Longer interval between abnormal tracing and delivery was associated with higher stillbirth rate. Active and adequate resuscitation of babies with abnormal tracing can reduce perinatal morbidity.

Timing Neonatal Hypoxic-Ischemic Encephalopathy

Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy initiated within six hours after birth effectively prevents neurodevelopmental impairments in some but not all infants. In part, this may be related to the timing of hypoxia before birth relative to the initiation of cooling. Metabolic acidosis at birth (suggesting acute hypoxia-ischemia) is required for treatment with hypothermia. However, placental evidence suggests that some infants also have chronic hypoxemia or poor perfusion before birth. Furthermore, although fetal distress is often noted during labor, timing the inciting event is difficult without a discrete sentinel event (such as umbilical cord prolapse). Another potential method of timing the onset of fetal hypoxia is through the evaluation of neonatal nucleated red blood cell counts. Fetal hypoxia induces production of erythropoietin and then nucleated red blood cells. These cells first appear in the blood at 24-36 hours after administration of darbepoetin in newborn infants,1Christensen R.D. Lambert D.K. Richards D.S. Estimating the nucleated red blood cell ‘emergence time’ in neonates.J Perinatol. 2014; 34: 116-119https://doi.org/10.1038/jp.2013.113Crossref PubMed Scopus (20) Google Scholar suggesting that elevated counts at birth reflect hypoxic events at least 24 hours earlier. In this volume of The Journal of Pediatrics, Bahr et al. report that infants with sentinel events during labor did not have elevated nucleated red cell counts at birth (>95% for age) and that normal counts were associated with somewhat better neurodevelopmental outcomes. Further work in this area, perhaps combined with biomarker studies and placental evaluations, may help researchers identify infants with a longer duration of fetal hypoxia who may not respond to therapeutic hypothermia alone. Research on new therapies could then be targeted to those who are most likely to benefit. Article page 12

Regulating DNA methylation could reduce neuronal ischemia response and apoptosis after ischemia-reperfusion injury

BackgroundIschemia-reperfusion injury (IRI) is an important pathophysiological condition that can cause cell injury and large-scale tissue injury in the nervous system. Previous studies have shown that epigenetic regulation may play a role in the pathogenesis of IRI. MethodsIn this study, we isolated mouse cortical neurons and constructed an oxygen-glucose deprivation/reoxygenation (OGD) model to explore the change in DNA methylation and its effect on the expression of corresponding genes. ResultsWe found that DNA methylation in neurons increased with hypoxia duration and that hypermethylation of numerous promoters and 3′-untranslated regions increased. We performed Gene Ontology enrichment analysis to study gene function and Kyoto Encyclopedia of Genes and Genomes pathway analysis to identify the pathways associated with gene regulation. The results showed that hypermethylation-related genes expressed after OGD were related to physiological pathways such as neuronal projection, ion transport, growth and development, while hypomethylation-related genes were related to pathological pathways such as the external apoptosis signaling pathway, neuronal death regulation, and regulation of oxidative stress. However, the changes in DNA methylation were specific for certain genes and may have been related to OGD-induced neuronal damage. Importantly, we integrated transcription and DNA methylation data to identify several candidate target genes, including hypomethylated Apoe, Pax6, Bmp4, and Ptch1 and hypermethylated Adora2a, Crhr1, Stxbp1, and Tac1. This study further indicated the effect of DNA methylation on gene function in brain IRI from the perspective of epigenetics, and the identified genes may become new targets for achieving neuroprotection in the brain after IRI.

Regional projection of climate warming effects on coastal seas in east China

The coastal region in east China experiences massive anthropogenic eutrophication, and the bottom water off the Changjiang River Estuary in the East China Sea faces the threat of severe seasonal hypoxia. We find that projected future climate changes will work in parallel with anthropogenic eutrophication to exacerbate current hypoxia and increase shelf vulnerability to bottom hypoxia. We use a coupled physical-biogeochemical regional model to investigate the differences of shelf hydrography and oxygen dynamics between present and future projected states. Model results indicate that the Yellow Sea Cold Water Mass which plays essential roles in nekton migration and shellfish farming practically disappears by the end of the 21st century, and shelf vertical stratification strengthens by an average of 12.7%. Hypoxia off the Changjiang River Estuary is exacerbated with increased (by one month) hypoxia duration, lower dissolved oxygen minima, and significant lateral (202%) and vertical (60%) expansions of hypoxic water. Reduced oxygen solubility, and accelerated oxygen consumption under increased primary production and rising water temperature contribute 42% and 58%, respectively, of bottom dissolved oxygen decrease in the East China Sea. Model results also show increased vertical diffusion of oxygen, despite vertical stratification strengthening, due to increased surface-bottom oxygen concentration gradient associated with increased oxygen release in surface water and exacerbated oxygen consumption in subsurface water.

Effects of Altitude and Duration of Differing Levels of Hypoxic Exposure on Hypoxia-Inducible Factor-1α in Rat Tissues.

Li, Xiao-lin, Wei-gang Wang, Mao-xing Li, Tian-long Liu, Xiu-yu Tian, and Lan Wu. Effects of altitude and duration of differing levels of hypoxic exposure on hypoxia-inducible factor-1α in rat tissues. High Alt Med Biol. 23:173-184, 2022. Objective: This research aimed to evaluate the effects of hypoxia at different altitudes and durations on the expression of hypoxia-inducible factor-1α (HIF-1α) in rat tissues. Methods: A total of 72 Wistar rats were used to investigate the effect of hypoxia at different durations on rat tissues and 72 Wistar rats were used to investigate the effect of hypoxia at different altitudes. Hematoxylin and Eosin (HE) staining was performed to observe the pathological changes of hippocampus tissues, and the expression of HIF-1α of rats under conditions of hypoxia was detected by quantitative real-time polymerase chain reaction and western blotting. Results: According to the pathological results, we found that the degree of the brain, lung, and heart damage and HIF-1α expression, showed an increasing trend as the altitude (1,500, 3,000, 4,500, 6,000, 7,500, and 8,000 m for 12 hours) and duration (0, 6, 12, 24, 36, and 72 hours at 7,500 m) of hypoxia increased. Although there is a significant difference at 8,000 m, considering model stability, animal ethics and cost, we chose 7,500 m as a fixed altitude during hypoxia at different durations. Compared with the normoxic group, the expression of HIF-1α mRNA in the 7,500 m significantly increased by 30.48%, 21.00%, and 12.62%, in brain, lung, and heart tissue (p < 0.01), and HIF-1α mRNA in the 72-hour hypoxic exposure group significantly increased by 52.58%, 20.39%, 27.88% in tissues (p < 0.05). Compared with the normoxic group, HIF-1α protein expressions in the 7,500 m significantly increased by 10.26%, 31.71%, and 13.33% in brain, lung, and heart tissue (p < 0.01, p < 0.01, p < 0.05), and HIF-1α protein expressions in the 72-hour hypoxic exposure group significantly increased by 18.89%, 22.89%, and 29.75% in tissues (p < 0.05). Conclusion: HIF-1α expression in the rat was correlated with altitude and duration of hypoxic exposure.

Executive Functions and Mood States in Athletes Performing Exercise Under Hypoxia.

Hypoxia can impair cognitive performance, whereas exercise can enhance it. The effects of hypoxia on cognitive performance during exercise appear to be moderated by exercise duration and intensity and by severity and duration of hypoxia and cognitive task. In normal individuals, exercise under hypoxia can evoke adverse post-exercise mood states, such as tension and fatigue. However, little is known about the effects of hypoxia during exercise in trained athletes. The purpose of this study was to investigate how hypoxia affected executive functions and mood states, assessed, respectively, during and post-exercise and to explore the role of motivation moderators, such as inhibition and activation systems (BIS-BAS). Two different sessions of exercise in normoxia and hypoxia (FiO2 13%), each lasting 18 min, were randomly assigned in a counterbalanced order and administered to seventeen male athletes. During exercise bouts, participants performed a mental task (BST) aimed to produce cognitive interference and suppression. Reaction times and accuracy of responses were recorded. After 5 min, all participants completed two questionnaires assessing mood states (ITAMS) and incidence of symptoms potentially related to hypoxia (AMS-C). The results show that hypoxia impairs cognitive performance in terms of slower reaction times, but a high BAS attenuates this effect. Participants with high BAS show an equivalent cognitive performance under hypoxia and normoxia conditions. No effects were found on mood states. Further research is required to investigate the role of BAS, cognitive abilities, and mood states in prolonged hypoxic conditions.