Increase In Oxygen Tension Research Articles

Electroacupuncture improves articular microcirculation and attenuates cartilage hypoxia in a male rabbit model of knee osteoarthritis

Background and aimHypoxia of the cartilage has been considered as a potential pathogenic factor in knee osteoarthritis (KOA). Studies have shown that impaired blood perfusion of joint leads to cartilage hypoxia. Electroacupuncture (EA) has proven effects on pain relief and improving microcirculation. This study aimed to explore the effect of EA on articular microcirculation and cartilage anoxic and the underlying mechanisms. ProceduresVideman's method was used for 6 weeks to establish the KOA model. EA intervention was performed in four points around the knee for 3 weeks after KOA modeling. The Lequesne MG score was used to assess ethology. We recorded the oxygen tension of synovial fluid and the synovial microcirculation in vivo. HE-staining was used to assess cartilage morphology, and immunohistochemistry (IHC), Western blotting, and RT-PCR were used to assess expression of the major glycolytic enzymes glucosetransporter1 (GLUT1), pyruvate kinase M2(PKM2), and lactate dehydrogenase A (LDHA). Enzyme-linked immunosorbent assay (Elisa) was used to detect lactate content. Results and conclusionThere was a significant decrease in Lequesne MG score and improvement in Mankin score after EA intervention (P < 0.01), a significant increase in synovial microcirculation (P < 0.05) and synovial fluid oxygen tension (P < 0.01), and there was significant decrease in the expression of GLUT1, PKM2 and LDHA (P < 0.01) and lactate (P < 0.05). This study suggested that EA ameliorate cartilage hypoxia and regulate glycolytic metabolism in chondrocytes in KOA model rabbits by improving articular microcirculation and oxygen tension.

Ozone Therapy for Breast Cancer: An Integrative Literature Review.

Breast cancer is the most prevalent form of cancer in women. Despite significant advances in conventional treatment, additional safer complementary treatment options are needed. Recently, ozone therapy has been considered as a type of medical adjunctive treatment that could inhibit cancer cell survival and reduce chemoresistance. However, only a few studies have been conducted on its use in breast cancer, and the optimal dosage and time of administration are unknown. Currently, preclinical studies suggest that ozone alone or in combination with chemotherapy is an effective method for inhibiting breast cancer cell growth. However, rather than investigating the effects of ozone as an antitumor therapy, current clinical trials have generally assessed its effect as an adjunctive therapy for reducing chemotherapy-induced side effects, increasing oxygen tension, normalizing blood flow, restoring blood lymphocytes more rapidly, and reducing fatigue symptoms. In this article, the use of ozone as a medical adjunctive treatment for breast cancer and its role in integrative therapy are summarized and discussed.

Neurogenic Regulation of Cerebral Blood Flow

The brain has a well-developed vascular network, which allows it to consume up to 15% of the cardiac output with a low mass relative to the whole-body weight. Normally, the metabolic demands of the brain depend considerably on the intensity of functioning of its different departments, which requires constant regulation of the local blood flow level. On the other hand, the state of systemic hemodynamics can have a significant impact on the organ blood flow. Complex and multilevel mechanisms of the regulation of organ cerebral blood flow are aimed at minimizing the possible adverse effects of systemic hemodynamics impairment. The importance of precise and prompt regulation of cerebral blood flow is reinforced by the absence of energy reserves or substrates for its autonomous production in the nervous tissue. The main mechanisms of cerebral blood flow regulation include: myogenic regulation, influence of local humoral influences and vasoactive substances (hormones, metabolites) of systemic blood flow, changes in blood gas composition (increase or decrease in blood oxygen or carbon dioxide tension). In addition, endothelium-dependent mechanisms of regulation are distinguished. Finally, one more level of cerebral arterial tone regulation is represented by the effect of neurotransmitters released from vasomotor fibers terminals of sympathetic and parasympathetic sections of autonomic nervous system, as well as from subcortical neurons and cortical interneurons terminals. In the present review, the principles of neurogenic regulation of cerebral blood flow are considered. The neurogenic regulation of vascular tone is the most complex regulatory circuit. The autonomic innervation of cerebral vessels has significant features that distinguish it from that in most other organs of the great circulatory circle. In addition to the autonomic innervation proper, the vessels of the brain receive sensory innervation, and the small intracerebral arterioles are also innervated -directly by subcortical neurons and cortical interneurons. In this connection, a deeper understanding of the molecular mechanisms of the neurogenic regulation of cerebral blood flow may serve as a basis for the development of new methods of treatment of severe brain diseases based on neuromodulation in the long term.

Mathematical model for glutathione dynamics in the retina

The retina is highly susceptible to the generation of toxic reactive oxygen species (ROS) that disrupt the normal operations of retinal cells. The glutathione (GSH) antioxidant system plays an important role in mitigating ROS. To perform its protective functions, GSH depends on nicotinamide adenine dinucleotide phosphate (NADPH) produced through the pentose phosphate pathway. This work develops the first mathematical model for the GSH antioxidant system in the outer retina, capturing the most essential components for formation of ROS, GSH production, its oxidation in detoxifying ROS, and subsequent reduction by NADPH. We calibrate and validate the model using experimental measurements, at different postnatal days up to PN28, from control mice and from the rd1 mouse model for the disease retinitis pigmentosa (RP). Global sensitivity analysis is then applied to examine the model behavior and identify the pathways with the greatest impact in control compared to RP conditions. The findings underscore the importance of GSH and NADPH production in dealing with oxidative stress during retinal development, especially after peak rod degeneration occurs in RP, leading to increased oxygen tension. This suggests that stimulation of GSH and NADPH synthesis could be a potential intervention strategy in degenerative mouse retinas with RP.

ПРИМЕНЕНИЕ ГИПЕРБАРИЧЕСКОЙ ОКСИГЕНОТЕРАПИИ В КОМПЛЕКСНОМ ЛЕЧЕНИИ ЖЕЛЕЗОДЕФИЦИТНОЙ ПОСЛЕРОДОВОЙ АНЕМИИ

Iron deficiency is the most common cause of postpartum anemia due to food habits, insufficient maternal iron reserves at the beginning of pregnancy, in-creased iron requirements associated with pregnancy, and blood loss during childbirth. As a non-drug treatment the use of hyperbaric oxygen therapy (HBO) is proposed. The main essence of the action of HBO is reduced to a rapid in-crease in oxygen tension in tissues due to an increase in the amount of dissolved oxygen in the blood, an increase in its diffusion rate between the blood and the hypoxic tissue site. Non-specific adaptive reactions developing during the use of HBO provide a wide range of therapeutic effects. At the same time, along with the beneficial effect, hyperoxia can also have a toxic effect, the clinic of which de-pends on the duration of exposure, individual sensitivity to oxygen, on the influ-ence of concomitant factors: temperature environment, physical activity, density of the gas mixture. The implementation of the compensatory capabilities of HBO is promising only with timely optimal use of the method.

Increasing oxygen tension in tumor tissue using ultrasound sensitive O2 microbubbles.

Low tissue oxygenation significantly impairs the effectiveness of cancer therapy and promotes a more aggressive phenotype. Many strategies to improve tissue oxygenation have been proposed throughout the years, but only a few showed significant effects in clinical settings. We investigated stability and ultrasound pulse (UP) triggered oxygen release from phospholipid coated oxygen microbubbles (OMB) in vitro and in murine tumors in vivo using EPR oximetry. In solution, the investigated microbubbles are stable and responsive to ultrasound pulse. The addition of the OMB solution alone resulted in an increase in pO2 of approximately 70mmHg which was further increased for an additional 80mmHg after the application of UP. The in vivo kinetic study revealed a substantial, up to 120mmHg, increase in tumor pO2 after UP application and then pO2 was decreasing for 20min for intravenous injection and 15min for intratumoral injection. A significant increase was also observed in groups that received microbubbles filled with nitrogen and ultrasound pulse and OMB without UP, but the effect was much lower. Oxygen microbubbles lead to a decrease in HIF-1a and VEGF-A both at the level of mRNA and protein. Toxicity analysis showed that intravenous injection of OMB does not cause oxidative damage to the heart, liver, or kidneys. However, elevated levels of oxidative damage to lipids and proteins were observed short-term in tumor tissue. In conclusion, we have demonstrated the feasibility of oxygen microbubbles in delivering oxygen effectively and safely to the tumor in living animals. Such treatment might enhance the effectiveness of other anticancer therapies.

Enhancing bacterial cellulose production with hypoxia-inducible factors.

Komagataeibacter xylinus is an aerobic strain that produces bacterial cellulose (BC). Oxygen levels play a critical role in regulating BC synthesis in K. xylinus, and an increase in oxygen tension generally means a decrease in BC production. Fumarate nitrate reduction protein (FNR) and aerobic respiration control protein A (ArcA) are hypoxia-inducible factors, which can signal whether oxygen is present in the environment. In this study, FNR and ArcA were used to enhance the efficiency of oxygen signaling in K. xylinus, and globally regulate the transcription of the genome to cope with hypoxic conditions, with the goal of improving growth and BC production. FNR and ArcA were individually overexpressed in K. xylinus, and the engineered strains were cultivated under different oxygen tensions to explore how their overexpression affects cellular metabolism and regulation. Although FNR overexpression did not improve BC production, ArcA overexpression increased BC production by 24.0% and 37.5% as compared to the control under oxygen tensions of 15% and 40%, respectively. Transcriptome analysis showed that FNR and ArcA overexpression changed the way K. xylinus coped with oxygen tension changes, and that both FNR and ArcA overexpression enhanced the BC synthesis pathway. The results of this study provide a new perspective on the effect of oxygen signaling on growth and BC production in K. xylinus and suggest a promising strategy for enhancing BC production through metabolic engineering. KEY POINTS: • K. xylinus BC production increased after overexpression of ArcA • The young's modulus is enhanced by the ArcA overexpression • ArcA and FNR overexpression changed how cells coped with changes in oxygen tension.

Capnodynamic monitoring of lung volume and blood flow in response to increased positive end-expiratory pressure in moderate to severe COVID-19 pneumonia: an observational study

BackgroundThe optimal level of positive end-expiratory pressure (PEEP) during mechanical ventilation for COVID-19 pneumonia remains debated and should ideally be guided by responses in both lung volume and perfusion. Capnodynamic monitoring allows both end-expiratory lung volume ({text{EELV}}_{{{text{CO}}_{2} }}) and effective pulmonary blood flow (EPBF) to be determined at the bedside with ongoing ventilation.MethodsPatients with COVID-19-related moderate to severe respiratory failure underwent capnodynamic monitoring of {text{EELV}}_{{{text{CO}}_{2} }} and EPBF during a step increase in PEEP by 50% above the baseline (PEEPlow to PEEPhigh). The primary outcome was a > 20 mm Hg increase in arterial oxygen tension to inspired fraction of oxygen (P/F) ratio to define responders versus non-responders. Secondary outcomes included changes in physiological dead space and correlations with independently determined recruited lung volume and the recruitment-to-inflation ratio at an instantaneous, single breath decrease in PEEP. Mixed factor ANOVA for group mean differences and correlations by Pearson’s correlation coefficient are reported including their 95% confidence intervals.ResultsOf 27 patients studied, 15 responders increased the P/F ratio by 55 [24–86] mm Hg compared to 12 non-responders (p < 0.01) as PEEPlow (11 ± 2.7 cm H2O) was increased to PEEPhigh (18 ± 3.0 cm H2O). The {text{EELV}}_{{{text{CO}}_{2} }} was 461 [82–839] ml less in responders at PEEPlow (p = 0.02) but not statistically different between groups at PEEPhigh. Responders increased both {text{EELV}}_{{{text{CO}}_{2} }} and EPBF at PEEPhigh (r = 0.56 [0.18–0.83], p = 0.03). In contrast, non-responders demonstrated a negative correlation (r = − 0.65 [− 0.12 to − 0.89], p = 0.02) with increased lung volume associated with decreased pulmonary perfusion. Decreased (− 0.06 [− 0.02 to − 0.09] %, p < 0.01) dead space was observed in responders. The change in {text{EELV}}_{{{text{CO}}_{2} }} correlated with both the recruited lung volume (r = 0.85 [0.69–0.93], p < 0.01) and the recruitment-to-inflation ratio (r = 0.87 [0.74–0.94], p < 0.01).ConclusionsIn mechanically ventilated patients with moderate to severe COVID-19 respiratory failure, improved oxygenation in response to increased PEEP was associated with increased end-expiratory lung volume and pulmonary perfusion. The change in end-expiratory lung volume was positively correlated with the lung volume recruited and the recruitment-to-inflation ratio. This study demonstrates the feasibility of capnodynamic monitoring to assess physiological responses to PEEP at the bedside to facilitate an individualised setting of PEEP.Trial registration: NCT05082168 (18th October 2021).

A Rare Cause of Severe Biventricular Dyssynchrony During Venoarterial Extracorporeal Membrane Oxygenation for COVID-19 Respiratory Failure

A Rare Cause of Severe Biventricular Dyssynchrony During Venoarterial Extracorporeal Membrane Oxygenation for COVID-19 Respiratory Failure

RESTORATION OF THE STRUCTURAL AND FUNCTIONAL STATE OF ERYTHROCYTES AFTER HYPOTHERMIC STORAGE USING HUMAN CORD BLOOD LOW-MOLECULAR FRACTION AND THE DRUG ACTOVEGIN

One of the modern transfusiology tasks is to preserve the properties of erythrocytes after hypothermic storage. Worsening of their functional state due to the storage leads to deterioration of the transfusion medium quality and a number of clinical problems. Plausible protective effects of a human cord blood low-molecular fraction (CBF) and the Actovegin drug were evaluated in the present study in order to use them as components of recovery medium. Aim. The purpose of our study was to investigate the CBF and the Actovegin drug effect on erythrocytes morphology, energy balance, and oxygen transport function of erythrocytes after their hypothermic storage. Materials and methods. In the research erythrocyte mass from human donor blood was used, which was stored in hypothermia for 7–21 days. Every 7 days, the CBF or Actovegin (final concentration 0.6 mg/ml) were added to aliquots of erythrocyte mass and incubated for 1 h at 37 °C, followed by further studies. CBF was obtained from human cord blood by ultrafiltration and lyophilization. The erythrocytes morphology was assessed using light microscopy. The content of ATP and 2.3-DPG was determined by the amount of inorganic phosphorus and the photoelectrocalorimetric method. The indicators of erythrocytes oxygen transport function (saturation, oxygen and carbon dioxide tension) were assessed using an analyzer of blood gases and electrolytes IL GEM Premier - 3000. The ratio of hemoglobin forms was studied by photometry. Results. It was shown that both CBF and the Actovegin drug promoted to restore the morpho-functional characteristics of erythrocytes after 21 days of their storage at 24 °C. This was indicative as an increase in the normocytes number increase and restoration of oxygen tension, saturation, ATP and 2,3-DFG content, and normalization of the hemoglobin forms ratio. It was suggested that the mechanisms of the compared tested substances action were associated with ATP synthesis activation and 2,3-DFG formation. Conclusions. The use of media with containing CBF or the Actovegin drug enabled to restore effectively the properties of erythrocytes disturbed during their prolonged storage.

Преоксигенация: терминология, физиологические основы, техники проведения, методики повышения эффективности, особенности у критических пациентов, возможные риски

Преоксигенация является широко распространенным приемом перед индукцией в анестезию и интубацией трахеи, предназначенным для увеличения запасов кислорода в организме и, таким образом, замедления начала десатурации гемоглобина во время апноэ. Показателями эффективности преоксигенации являются увеличение фракции альвеолярного кислорода, увеличение напряжения кислорода в артериальной крови и снижение фракции альвеолярного азота. Конечная точка максимальной преоксигенации — концентрация кислорода в конце выдоха 90 % или концентрация азота в конце выдоха 5 %. Для проведения преоксигенации используются две техники: по дыхательному объему и путем глубоких вдохов. Существуют различные методики для улучшения эффекта преоксигенации. Они включают поднятие головы, апнойную диффузную оксигенацию, использование постоянного положительного давления/положительного давления конца выдоха, двухуровневое положительное давление в дыхательных путях и трансназальную увлажненную быструю инсуффляцию. Преоксигенация с высоким риском включает таких пациентов, как беременные женщины, пациенты, страдающие ожирением, дети, лица пожилого возраста, пациенты с сопутствующими легочными заболеваниями, пациенты на большой высоте. Потенциальные риски преоксигенации включают отсроченное определение пищеводной интубации, абсорбционный ателектаз, продукцию частиц активного кислорода и нежелательные гемодинамические эффекты. Так как преоксигенация по времени не продолжительна, гемодинамические эффекты и накопление частиц активного кислорода незначительны. Абсорбционный ателектаз является следствием преоксигенации. Для снижения риска возникновения абсорбционного ателектаза во время преоксигенации предложено два подхода: умеренное снижение фракции кислорода до 0,8 и использование рекрутмент-маневров, таких как постоянное положительное давление, положительное давление конца выдоха и/или маневры с жизненной емкостью легких. Хотя незначительное давление фракции кислорода уменьшает риск ателектазирования, это происходит за счет снижения кислородного резерва. Техника преоксигенации должна использоваться правильно, с мониторированием концентрации кислорода в конце выдоха. Анестезиолог должен быть ознакомлен с различными методиками проведения преоксигенации, выбирая наиболее подходящую.

Integrative Role of Hyperbaric Oxygen Therapy on Healthspan, Age-Related Vascular Cognitive Impairment, and Dementia.

Growing life expectancy will contribute to the on-going shift towards a world population increasingly comprised of elderly individuals. This demographic shift is associated with a rising prevalence of age-related diseases, among all age-related pathologies it has become crucial to understand the age-associated cognitive changes that remain a major risk factor for the development of vascular cognitive impairment and dementia (VCID). Furthermore, age-related Alzheimer’s disease and other neurogenerative diseases with vascular etiology are the most prominent contributing factors for the loss of cognitive function observed in aging. Hyperbaric Oxygen Therapy (HBOT) achieves physiologic effects by increasing oxygen tension (PO2), raising oxygen tissue levels, decreasing intracranial pressure and relieving cerebral edema. Many of the beneficial effects of HBOT exert their protective effects at the level of the microcirculation. Furthermore, the microcirculation’s exquisite pervasive presence across every tissue in the body, renders it uniquely able to influence the local environment of most tissues and organs, including the brain. As such, treatments aimed at restoring aging-induced functional and structural alterations of the cerebral microcirculation may potentially contribute to the amelioration of a range of age-related pathologies including vascular cognitive impairment, Alzheimer’s disease, and vascular dementias. Despite the presented evidence, the efficacy and safety of HBOT for the treatment of age-related vascular cognitive impairment and dementia remains understudied. The present review aims to examine the existing evidence indicative of a potential therapeutic role for HBOT-induced hyperoxia against age-related cerebromicrovascular pathologies contributing to cognitive impairment, dementia and decreased healthspan in the elderly.

PS-1. Future interaction among International Society of Hypertension (ISH), Japan Society of Hypertension (JSH) and ISSHP

Human pregnancy and in particular the first trimester, is a period highly susceptible towards adverse insults such as oxidative stress, which may lead to inadequate embryonic and feto-placental development. Diabetes mellitus is associated with increased oxidative stress caused by hyperglycemia, reactive oxygen species (ROS) production and inflammatory signals. In pregnancy, diabetes elevates the risk for early pregnancy loss, preeclampsia and fetal growth restriction, pathologies that origin from early placental maldevelopment. We hypothesized that maternal Type 1 diabetes mellitus (T1DM) induces oxidative stress in the first trimester human placenta.We quantified stress induced, cytoprotective proteins, i.e. heat shock protein (HSP)70 and heme oxygenase (HO)-1 and determined protein modifications as markers for oxidation and glycation, i.e. levels of 4-hydroxynonenal (HNE) or Nε-(carboxymethyl)lysine (CML) modified proteins. Moreover, we measured expression levels of enzymes involved in antioxidant defense in the first trimester (week 7–9) placenta of normal and T1DM women by immunoblot and real-time qPCR. Primary human trophoblasts were isolated from first trimester placenta and the effects of oxygen, hyperglycemia and the pro-inflammatory cytokine tumor necrosis factor (TNF)-α on levels of HSP70 and HO-1 were analyzed.HSP70 (+19.9± 10.1%) and HO-1 (+63.5± 14.5%) were elevated (p < 0.05) in first trimester placenta of T1DM women when compared to normal women. However, levels of HNE or CML modified proteins were unchanged. Also, expression of most antioxidant enzymes was unchanged, with only superoxide dismutase 3 (SOD3) being upregulated by 3.0-fold (p < 0.05). In isolated primary trophoblasts, HSP70 and HO-1 were upregulated by increasing oxygen tension, but not by hyperglycemia or TNF-α.Although protein oxidation and glycation was not elevated, we infer that T1DM increases placental cellular stress in the first trimester. Elevated stress in early placenta of T1DM women may contribute to disturbances in placental development.

SETD7 mediates the vascular invasion in articular cartilage and chondrocytes apoptosis in osteoarthriis.

The pathological characteristics of osteoarthritis are cartilage matrix degradation, chondrocytes apoptosis, and low-grade inflammation of the joint. Recent studies have shown that blood vessels grow from the subchondral bone to the articular cartilage. However, the relationship among inflammation, angiogenesis, and chondrocyte apoptosis is still unclear. We found that chondrocytes could secrete chemokines and VEGF to promote the migration of vascular endothelial cells in response to TNF-α stimulation. The invasion of blood vessels leads to increased oxygen tension in the local environment, which increased the expression of SETD7 in chondrocytes by activating the JAK-STAT5 pathway. The bond of phosphorylated STAT5 and the specific locus in the promoter of SETD7 directly increased the transcription of SETD7. On the one hand, SETD7-regulated chemokine expression by forming a positive loop; on the other hand, SETD7-mediated chondrocyte apoptosis by inhibiting the nuclear localization of HIF-1α. In this study, we discovered a novel function of chondrocytes as mediators of inflammation and angiogenesis. Our study demonstrates that SETD7 is a potential molecular target to prevent OA development and progression.

Biomarkers of Oxidative Stress for Neonatal Lung Disease.

The transition from prenatal to postnatal life causes a significant increase in arterial oxygen tension and the activation of metabolic pathways enabling the newborn's adaptation to the extra-uterine environment. The balance between pro-oxidant and anti-oxidant systems is critical to preserve cellular functions. Indeed, oxidative stress (OS) occurs when the production of free radicals is not balanced by the activity of intracellular antioxidant systems, contributing to cellular and tissue damage. Perinatal OS may have serious health consequences during the postnatal period and later in life. Namely, OS has been recognized as the major cause of lung injury in newborns, especially those preterm born, due to their immature lung and antioxidant systems. The development of OS biomarkers has gained increasing research interest since they may provide useful insights about pathophysiological pathways underlying OS-mediated pulmonary diseases in newborns. Moreover, their implementation in clinical settings may help to early identify high risk-newborns and to provide targeted treatment. Ideally, a biomarker should demonstrate ease of use, biological validity and reproducibility, high sensitivity and specificity. However, none of the clinically validated biomarkers so far have been qualified for neonatal lung disease. Additionally, the complex technical procedures and the high cost of such determinations have hampered the use of OS biomarkers in clinical practice. This review aims to evaluate the current evidence on the application of biomarkers of oxidative stress for neonatal lung disease and exploring the most relevant issues affecting their implementation in practice, as well as the associated evidence gaps and research limitations.

Smoking and Nicotine Effects on Surgery: Is Nicotine Replacement Therapy (NRT) a Safe Option?

Smoking and Nicotine Effects on Surgery: Is Nicotine Replacement Therapy (NRT) a Safe Option?

Early Chronic Intermittent Maternal Hyperoxygenation Impairs Cortical Development by Inhibition of Pax6-Positive Apical Progenitor Cell Proliferation.

Maternal hyperoxygenation is a feasible, noninvasive method to treat fetal diseases, such as heart hypoplasia, but effects of maternal hyperoxygenation on the developing brain remain poorly understood. Previous studies showed that short-term maternal hyperoxygenation during midneurogenic phase (E14-E16) but not in earlier development (E10-E12) increases oxygen tension and enhances neurogenesis in the developing mouse cortex. We investigated effects of early chronic maternal hyperoxygenation (CMH) as a potential clinical treatment. Pregnant C57BL/6J mice were housed in a chamber at 75% atmospheric oxygen and the brains of E16 fetuses were analyzed using immunohistochemistry. The mitosis marker phH3 showed a significant reduction of proliferation in the dorsolateral cortices of CMH-treated E16 fetuses. Numbers of Tbr2-positive intermediate progenitor cells were unaffected whereas numbers of Pax6-positive apical progenitor cells were significantly reduced in CMH-treated mice. This resulted in altered cortical plate development with fewer Satb2-positive upper layer neurons but more Tbr1-positive neurons corresponding to the deeper layer 6. Thus, maternal hyperoxygenation affects the developing cortex depending on timing and length of applied oxygen. Early CMH causes a severe reduction of neuroprogenitor proliferation likely affecting cortical development. Further studies are needed to investigate the mechanisms underlying these findings and to assess the clinical and neurodevelopmental outcomes of the pups.

Different Dosage Effects of Ozone on Oxygen Transport in Blood during in vitro Experiments

The effects of ozone on oxygen transport in the blood of experimental animals have been studied in vitro. Incubation of the blood with ozonated water at О3 concentrations of 2, 6, and 10 mg/L for 30 and 60 min caused changes in the oxygen-transport function of the blood, thus leading to increased oxygen tension and oxygenation, as well as reduced affinity of hemoglobin for oxygen. As a result, the content of the gaseous transmitters, such as nitric oxide and hydrogen sulfide, significantly increased, thus contributing to modification of the oxygen-binding properties of blood.

HYPOXIA INDUCES TROPHOBLAST MIGRATION AND INVASION GENE PATHWAYS A SUBSET OF WHICH ARE REDUCED IN PREECLAMPSIA CVS

At the start of pregnancy, trophoblasts (TBs) migrate and invade into the decidua and remodel the spiral arteries in physiologic hypoxic conditions (1-3% O2). Persistent hypoxia secondary to a defect in remodeling of the maternal arteries is proposed to lead to a failure to increase oxygen tension, leading to poor placental perfusion and pregnancy complications, such as preeclampsia (PE). The objectives of this study are to determine how exposure to hypoxia impacts gene expression and cellular motility of first trimester TBs, and to assess if expression of migration-associated genes is dysregulated in 2nd trimester chorionic villous samples (CVS) from PE pregnancies relative to CVS from healthy pregnancies.

Brain Tissue Oxygen Response as Indicator for Cerebral Lactate Levels in Aneurysmal Subarachnoid Hemorrhage Patients.

Early detection of cerebral ischemia and metabolic crisis is crucial in critically ill subarachnoid hemorrhage (SAH) patients. Variable increases in brain tissue oxygen tension (PbtO2) are observed when the fraction of inspired oxygen (FiO2) is increased to 1.0. The aim of this prospective study was to evaluate whether a 3-minute hyperoxic challenge can identify patients at risk for cerebral ischemia detected by cerebral microdialysis. Twenty consecutive severe SAH patients undergoing continuous cerebral PbtO2 and microdialysis monitoring were included. FiO2 was increased to 1.0 for 3 minutes (the FiO2 challenge) twice a day and PbtO2 responses during the FiO2 challenges were related to cerebral microdialysis-measures, ie, lactate, the lactate-pyruvate ratio, and glycerol. Multivariable linear and logistic regression models were created for each outcome parameter. After predefined exclusions, 274 of 400 FiO2 challenges were included in the analysis. Lower absolute increases in PbtO2 (∆PbtO2) during FiO2 challenges were significantly associated with higher cerebral lactate concentration (P<0.001), and patients were at higher risk for ischemic lactate levels >4 mmol/L (odds ratio 0.947; P=0.04). Median (interquartile range) ∆PbtO2 was 7.1 (4.6 to 12.17) mm Hg when cerebral lactate was >4 mmol/L and 10.2 (15.76 to 14.24) mm Hg at normal lactate values (≤4 mmol/L). Median ∆PbtO2 was significantly lower during hypoxic than during hyperglycolytic lactate elevations (4.6 vs. 10.6 mm Hg, respectively; P<0.001). Lactate-pyruvate ratio and glycerol levels were mainly determined by baseline characteristics. A 3-minute FiO2 challenge is an easy to perform and feasible bedside diagnostic tool in SAH patients. The absolute increase in PbtO2 during the FiO2 challenge might be a useful surrogate marker to estimate cerebral lactate concentrations and might be used to identify patients at risk for impending ischemia.