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Background: Patients with respiratory disease often need oxygen supplements through a High‐flow nasal cannula (HFNC), both hypoxia and hyperoxia can be harmful. Proper oxygen therapy requires careful monitoring of oxygen levels and adjustments to oxygen levels. A new automated system called Targeted SpO2 Feedback (TSF) improved the oxygen delivery system compared to manual adjustments. [Correction added on 25 October 2024, after first online publication: Background subsection in Abstract has been added on this version.] Aim: To test whether targeted SpO2 feedback (TSF), an automatic control system for fraction of inspired oxygen (FiO2), achieves more time in the optimal SpO2 range and/or reduces the frequency of manual adjustments to administered FiO2 compared with conventional manual titration in patients with hypoxia on high‐flow nasal cannula (HFNC) therapy. Study Design: Twenty‐two patients were recruited from two hospitals. For each, two sessions of manual mode and two sessions of TSF were applied in a random order, each session lasting 2 h. The target SpO2 on TSF was 95%. Oxygen monitoring levels were classified into four SpO2 ranges: hypoxia (≤ 89%), borderline (90%–93%), optimal (94%–96%) and hyperoxia (≥ 97%). The two modes were compared based on the proportion of time spent in each SpO2 range and the number of manual FiO2 adjustments. Results: The proportion of time in the optimal SpO2 range was 20.5% under manual titration mode and 65.4% under TSF (p <.01). The proportions of time in the hypoxia range were 1.1% and 0.4%, respectively (p =.31), in the borderline range 4.7% and 3.5%, respectively (p =.54), and in the hyperoxia range 73.7% and 30.7%, respectively (p <.01). There were statistical differences only in the optimal and hyperoxia SpO2 ranges. During the 8 h, the frequency of manual FiO2 adjustment was 0.7 times for the manual mode and 0.2 times for TSF, showing no statistically significant difference (p = 0.076). Conclusion: Compared with manual titration, TSF achieved greater time of the optimal SpO2 and less time of hyperoxia during HFNC. The frequency of manual adjustments on TSF tended to be less than on manual titration mode. Relevance to Clinical Practice: Automatic closed‐loop algorithm FiO2 monitoring systems can achieve better oxygen treatments than conventional monitoring and may reduce nurse workloads. In the era of pandemic respiratory diseases, this system can also facilitate contactless SpO2 monitoring during HFNC therapy. [ABSTRACT FROM AUTHOR]

Preclinical work supports a role for the peripheral chemoreceptors in the progression of cardiovascular and metabolic pathologies. In the present study, we examined peripheral chemosensitivity in adults with type 2 diabetes (T2D) and the contribution of the peripheral chemoreceptors to resting cardiovascular and metabolic control. We hypothesized that: (1) adults with T2D exhibit exaggerated peripheral chemoreflex sensitivity; (2) the peripheral chemoreceptors contribute to cardiovascular dysfunction in T2D; and (3) attenuation of peripheral chemoreceptor activity improves glucose tolerance in T2D. Seventeen adults with diagnosed T2D [six males/11 females; aged 54 ± 11 years; glycated haemoglobin (HbA1c) 7.6 ± 1.5%] and 20 controls without T2D (9 males/11 females; aged 49 ± 13 years, HbA1c 5.2 ± 0.4%) participated in the study. The hypoxic ventilatory response (HVR) was assessed as an index of peripheral chemosensitivity. Resting heart rate, blood pressure and minute ventilation were measured when breathing normoxic followed by hyperoxic air (1.0FIO2${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$) to acutely attenuate peripheral chemoreceptor activity. A subset of participants (n = 9 per group) completed two additional visits [normoxia (0.21FIO2${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$), hyperoxia (1.0FIO2${{F}_{{\mathrm{I}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$)] where glucose and insulin were measured for 2 h following an oral glucose challenge. HVR was augmented in adults with T2D (–0.84 ± 0.49 L min–1/%) vs. control (–0.48 ± 0.40 L min–1/%, P = 0.021). Attenuation of peripheral chemoreceptor activity decreased heart rate (P < 0.001), mean blood pressure (P = 0.009) and minute ventilation (P = 0.002); any effect of hyperoxia did not differ between groups. There was no effect of hyperoxia on the glucose (control, P = 0.864; T2D, P = 0.982), nor insulin (control, P = 0.763; T2D, P = 0.189) response to the oral glucose challenge. Peripheral chemoreflex sensitivity is elevated in adults with T2D; however, acute attenuation of peripheral chemoreflex activity with hyperoxia does not restore cardiometabolic function. Key points: Preclinical work supports a role for the peripheral chemoreceptors in the progression of cardiovascular and metabolic pathologies. In the present study, we examined peripheral chemosensitivity in adults with type 2 diabetes and the contribution of the peripheral chemoreceptors to resting cardiovascular control and glucose tolerance. We observed elevated peripheral chemoreflex sensitivity in adults with diabetes which was associated with glycaemic control (i.e. glycated haemoglobin). Notably, acute attenuation of peripheral chemoreflex activity with hyperoxia did not restore cardiometabolic function in the individuals studied. [ABSTRACT FROM AUTHOR]

Nuclear factor‐erythroid‐2‐related factor‐2 (NRF‐2) is a cellular resistance protein to oxidants. We investigated the effect of exogenous all‐trans retinoic acid (ATRA) on the antioxidant system and NRF‐2 in mice kidneys under hyperoxia‐induced oxidative stress. Mice were divided into four groups. Daily, two groups were given either peanut‐oil/dimethyl sulfoxide (PoDMSO) mixture or 50 mg/kg ATRA. Oxidative stress was induced by hyperoxia in the remaining groups. They were treated with PoDMSO or ATRA as described above, following hyperoxia (100% oxygen) for 72 h. NRF‐2 and active‐caspase‐3 levels, lipid peroxidation (LPO), activities of antioxidant enzymes, xanthine oxidase (XO), paraoxonase1 (PON1), lactate dehydrogenase (LDH), tissue factor (TF), and prolidase were assayed in kidneys. Hyperoxia causes kidney damage induced by oxidative stress and apoptosis. Increased LPO, LDH, TF, and XO activities and decreased PON1 and prolidase activities contributed to kidney damage in hyperoxic mice. After hyperoxia, increases in the activities of antioxidant enzymes and NRF‐2 level could not prevent this damage. ATRA attenuated damage via its oxidative stress‐lowering effect. The decreased LDH and TF activities increased PON1 and prolidase activities, and normalized antioxidant statuses are indicators of the positive effects of ATRA. We recommend that ATRA can be used as a renoprotective agent against oxidative stress induced‐kidney damage. Significance Statement: This study investigates the protective effects of all‐trans retinoic acid (ATRA) against oxidative stress and oxidative stress‐induced tissue damage in mouse kidneys. Exposure to high oxygen levels significantly damages kidney tissues by increasing lipid peroxidation and enzyme activities, leading to cellular dysfunction. However, treatment with ATRA demonstrated a remarkable ability to attenuate these effects, increase the activity of antioxidant defenses, and stabilize essential renal enzymes. These findings suggest that ATRA may be a potent renoprotector and offer a promising approach to managing oxidative stress‐induced renal damage. [ABSTRACT FROM AUTHOR]

Supplemental O2 (hyperoxia) is a critical intervention for premature infants (<34 weeks) but consequently is associated with development of bronchial airway hyperreactivity (AHR) and asthma. Clinical practice shifted toward the use of moderate hyperoxia (<60% O2), but risk for subsequent airway disease remains. In mouse models of moderate hyperoxia, neonatal mice have increased AHR with effects on airway smooth muscle (ASM), a cell type involved in airway tone, bronchodilation, and remodeling. Understanding mechanisms by which moderate O2 during the perinatal period initiates sustained airway changes is critical to drive therapeutic advancements toward treating airway diseases. We propose that cellular clock factor BMAL1 is functionally important in developing mouse airways. In adult mice, cellular clocks target pathways highly relevant to asthma pathophysiology and Bmal1 deletion increases inflammatory response, worsens lung function, and impacts survival outcomes. Our understanding of BMAL1 in the developing lung is limited, but our previous findings show functional relevance of clocks in human fetal ASM exposed to O2. Here, we characterize Bmal1 in our established mouse neonatal hyperoxia model. Our data show that Bmal1 KO deleteriously impacts the developing lung in the context of O2 and these data highlight the importance of neonatal sex in understanding airway disease. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of inhaled oxygen level on dynamic glucose enhanced (DGE) MRI in mouse brain tissue and CSF at 3 T. Methods: DGE data of brain tissue and CSF from mice under normoxia or hyperoxia were acquired in independent and interleaved experiments using on‐resonance variable delay multi‐pulse (onVDMP) MRI. A bolus of 0.15 mL filtered 50% D‐glucose was injected through the tail vein over 1 min during DGE acquisition. MRS was acquired before and after DGE experiments to confirm the presence of D‐glucose. Results: A significantly higher DGE effect under normoxia than under hyperoxia was observed in brain tissue (p = 0.0001 and p = 0.0002 for independent and interleaved experiments, respectively), but not in CSF (p > 0.3). This difference is attributed to the increased baseline MR tissue signal under hyperoxia induced by a shortened T1 and an increased BOLD effect. When switching from hyperoxia to normoxia without glucose injection, a signal change of ˜3.0% was found in brain tissue and a signal change of ˜1.5% was found in CSF. Conclusions: DGE signal was significantly lower under hyperoxia than that under normoxia in brain tissue, but not in CSF. The reason is that DGE effect size of brain tissue is affected by the baseline signal, which could be influenced by T1 change and BOLD effect. Therefore, DGE experiments in which the oxygenation level is changed from baseline need to be interpreted carefully. [ABSTRACT FROM AUTHOR]

The mechanisms governing brain vascularization during development remain poorly understood. A key regulator of developmental vascularization is delta like 4 (DLL4), a Notch ligand prominently expressed in endothelial cells (EC). Exposure to hyperoxia in premature infants can disrupt the development and functions of cerebral blood vessels and lead to long‐term cognitive impairment. However, its role in cerebral vascular development and the impact of postnatal hyperoxia on DLL4 expression in mouse brain EC have not been explored. We determined the DLL4 expression pattern and its downstream signalling gene expression in brain EC using Dll4+/+ and Dll4+/LacZ mice. We also performed in vitro studies using human brain microvascular endothelial cells. Finally, we determined Dll4 and Cldn5 expression in mouse brain EC exposed to postnatal hyperoxia. DLL4 is expressed in various cell types, with EC being the predominant one in immature brains. Moreover, DLL4 deficiency leads to persistent abnormalities in brain microvasculature and increased vascular permeability both in vivo and in vitro. We have identified that DLL4 insufficiency compromises endothelial integrity through the NOTCH‐NICD‐RBPJ‐CLDN5 pathway, resulting in the downregulation of the tight junction protein claudin 5 (CLDN5). Finally, exposure to neonatal hyperoxia reduces DLL4 and CLDN5 expression in developing mouse brain EC. We reveal that DLL4 is indispensable for brain vascular development and maintaining the blood–brain barrier's function and is repressed by neonatal hyperoxia. We speculate that reduced DLL4 signalling in brain EC may contribute to the impaired brain development observed in neonates exposed to hyperoxia. Key points: The role of delta like 4 (DLL4), a Notch ligand in vascular endothelial cells, in brain vascular development and functions remains unknown.We demonstrate that DLL4 is expressed at a high level during postnatal brain development in immature brains and DLL4 insufficiency leads to abnormal cerebral vasculature and increases vascular permeability both in vivo and in vitro.We identify that DLL4 regulates endothelial integrity through NOTCH‐NICD‐RBPJ‐CLDN5 signalling.Dll4 and Cldn5 expression are decreased in mouse brain endothelial cells exposed to postnatal hyperoxia. [ABSTRACT FROM AUTHOR]

Quercetin, a bioactive natural compound renowned for its potent anti‐inflammatory, antioxidant, and antiviral properties, has exhibited therapeutic potential in various diseases. Given that bronchopulmonary dysplasia (BPD) development is closely linked to inflammation and oxidative stress, and quercetin, a robust antioxidant known to activate NRF2 and influence the ferroptosis pathway, offers promise for a wide range of age groups. Nonetheless, the specific role of quercetin in BPD remains largely unexplored. This study aims to uncover the target role of quercetin in BPD through a combination of network pharmacology, molecular docking, computer analyses, and experimental evaluations. [ABSTRACT FROM AUTHOR]

Objectives: Blood‐oxygen‐level‐dependent (BOLD) magnetic resonance imaging (MRI) facilitates the non‐invasive in‐vivo evaluation of placental oxygenation. The aims of this study were to identify and quantify a relative BOLD effect in response to hyperoxia in the human placenta and to compare it between pregnancies with and those without fetal growth restriction (FGR). Methods: This was a prospective multicenter study (NCT02238301) of 19 pregnancies with FGR (estimated fetal weight (EFW) on ultrasound < 5th centile) and 75 non‐FGR pregnancies (controls) recruited at two centers in Paris, France. Using a 1.5‐Tesla MRI system, the same multi‐echo gradient‐recalled echo (GRE) sequences were performed at both centers to obtain placental T2* values at baseline and in hyperoxic conditions. The relative BOLD effect was calculated according to the equation 100 × (hyperoxic T2* − baseline T2*)/baseline T2*. Baseline T2* values and relative BOLD effect were compared according to EFW (FGR vs non‐FGR), presence/absence of Doppler anomalies and birth weight (small‐for‐gestational age (SGA) vs non‐SGA). Results: We observed a relative BOLD effect in response to hyperoxia in the human placenta (median, 33.8% (interquartile range (IQR), 22.5–48.0%)). The relative BOLD effect did not differ significantly between pregnancies with and those without FGR (median, 34.4% (IQR, 24.1–48.5%) vs 33.7% (22.7–47.4%); P = 0.95). Baseline T2* Z‐score adjusted for gestational age at MRI was significantly lower in FGR pregnancies compared with non‐FGR pregnancies (median, −1.27 (IQR, −4.87 to −0.10) vs 0.33 (IQR, −0.81 to 1.02); P = 0.001). Baseline T2* Z‐score was also significantly lower in those pregnancies that subsequently delivered a SGA neonate (n = 23) compared with those that delivered a non‐SGA neonate (n = 62) (median, −0.75 (IQR, −3.48 to 0.29) vs 0.35 (IQR, −0.79 to 1.05); P = 0.01). Conclusions: Our study confirms a BOLD effect in the human placenta and that baseline T2* values are significantly lower in pregnancies with FGR. Further studies are needed to evaluate whether such parameters may detect placental insufficiency before it has a clinical impact on fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a common cerebrovascular disease, and the complement cascade exacerbates brain injury after ICH. As the most abundant component of the complement system, complement component 3 (C3) plays essential roles in all three complement pathways. However, the effects of C3 on neurological impairment and brain injury in ICH patients and the related mechanism have not been fully elucidated. Normobaric hyperoxia (NBO) is regarded as a treatment for ICH patients, and recent clinical studies also have confirmed the neuroprotective role of NBO against acute ICH‐mediated brain damage, but the underlying mechanism still remains elusive. Aims: In the present study, we investigated the effects of complement C3 on NBO‐treated ICH patients and model mice, and the underlying mechanism of NBO therapy in ICH‐mediated brain injury. Results: Hemorrhagic injury resulted in the high plasma C3 levels in ICH patients, and the plasma C3 levels were closely related to hemorrhagic severity and clinical outcomes after ICH. BO treatment alleviated neurologic impairments and rescued the hemorrhagic‐induced increase in plasma C3 levels in ICH patients and model mice. Moreover, the results indicated that NBO exerted its protective effects of on brain injury after ICH by downregulating the expression of C3 in microglia and alleviating microglia‐mediated synaptic pruning. Conclusions: Our results revealed that NBO exerts its neuroprotective effects by reducing C3‐mediated synaptic pruning, which suggested that NBO therapy could be used for the clinical treatment of ICH. [ABSTRACT FROM AUTHOR]

The article focuses on the use of supplemental oxygen in paediatric intensive care units (PICUs) and compares the effects of higher and lower target oxygen saturation levels on critically ill children. It discusses the findings of a pragmatic, multicentre, open-label, randomised controlled trial conducted in 15 UK PICUs, which showed a slight benefit for the lower target saturation strategy over the higher target saturation strategy.

Different interventions can independently improve athletic performance via different central or peripheral mechanisms, but little is known about their potential combination. We tested the effects of seven combined interventions (enhanced recovery package [ERP]) on performance during intermittent high‐intensity cycling compared with placebo. Sixteen trained men (maximal power output: 5.0 ± 0.5 W･kg−1) completed six 30‐s cycling sprints with 3‐min breaks in‐between under ERP, placebo, and control conditions. The ERP combined neck cooling, carbohydrate and caffeine mouth rinsing, carbohydrate and water ingestion, hyperventilation, hyperoxia, and potentiation maneuvers. Power output, heart rate, blood lactate concentration, rate of perceived exertion, and gas exchange were compared between the ERP and placebo conditions. Mean power output was higher during ERP compared with placebo (570 ± 74 W vs. 560 ± 71 W, p < 0.001, dz = 1.15). Heart rate was higher (+3 ± 4 bpm, p = 0.012) during ERP, as was breathing frequency (+2.4 ± 4.0 breaths･min−1, p = 0.028) and respiratory exchange ratio (+0.12 ± 0.06, p < 0.001). Oxygen uptake was 80 ± 109 mL･min−1 lower (p = 0.013) for ERP. No differences were found with regards to the rate of perceived exertion or blood lactate concentration. Performance gains with ERP were small in magnitude but consistent across individuals. The ERP might have prevented a loss of aerobic efficiency or increased reliance on anaerobic energy. Testing combined interventions might increase the chances to see beyond daily variability in practice. Highlights: Combining seven different ergogenic interventions boosted repeated sprint performance by approximately 1.8% compared with placebo in trained individuals, suggesting that gains from single interventions are not cumulative.Fifteen out of 16 participants showed improved performance with the combined interventions, suggesting that the benefit of the combination might reside in the consistency of the gains obtained across individuals.The increase in power output with the ergogenic interventions took place despite lower oxygen uptake, suggesting either a maintenance of aerobic efficiency or increased reliance on anaerobic energy.A top‐down approach might be interesting for coaches and athletes trying to identify a set of interventions that improve performance, which can then be tailored to remove the ones that are least practical or least appreciated. [ABSTRACT FROM AUTHOR]

Mechanisms underlying hyperoxia‐induced airflow restriction in the pediatric lung disease Bronchopulmonary dysplasia (BPD) are unclear. We hypothesized a role for Renin‐Angiotensin System (RAS) activity in BPD. RAS is comprised of a pro‐developmental pathway consisting of angiotensin converting enzyme‐2 (ACE2) and angiotensin II receptor type 2 (AT2), and a pro‐fibrotic pathway mediated by angiotensin II receptor type 1 (AT1). We investigated associations between neonatal hyperoxia, airflow restriction, and RAS activity in a BPD mouse model. C57 mouse pups were randomized to normoxic (FiO2 = 0.21) or hyperoxic (FiO2 = 0.75) conditions for 15 days (P1–P15). At P15, P20, and P30, we measured airflow restriction using plethysmography and ACE2, AT1, and AT2 mRNA and protein expression via polymerase chain reaction and Western Blot. Hyperoxia increased airflow restriction P15 and P20, decreased ACE2 and AT2 mRNA, decreased AT2 protein, and increased AT1 protein expression. ACE2 mRNA and protein remained suppressed at P20. By P30, airflow restriction and RAS expression did not differ between groups. Hyperoxia caused high airflow restriction, increased pulmonary expression of the pro‐fibrotic RAS pathway, and decreased expression of the pro‐developmental in our BPD mouse model. These associated findings may point to a causal role for RAS in hyperoxia‐induced airflow restriction. [ABSTRACT FROM AUTHOR]

Leatherback egg clutches typically experience lower hatching success (~50%) than those of other sea turtle species (>70%). The majority of embryonic death (>50%) occurs at early stages of development, possibly because embryos fail to break preovipositional embryonic arrest after oviposition. The embryonic arrest is maintained by hypoxia in the oviduct and following oviposition increased availability of oxygen is the trigger that breaks arrest in all turtle species studied to date. We conducted an ex situ incubator experiment and an in situ hatchery experiment to examine the influence of oxygen availability on hatching success and hatchling traits in leatherbacks. After oviposition, eggs (n = 1005) were incubated in either normoxia (21% O2), hyperoxia (32%–42% O2) for 5 days, or hypoxia (1% O2) for 3 or 5 days. As with other turtles, hypoxic incubation maintained embryos in arrest, equivalent to the time spent in hypoxia. However, extending arrest for 5 days resulted in greater early‐stage death and a significant decrease in hatching success (4% 5‐day hypoxia vs. 72% normoxia). Eggs placed in incubators had greater hatching success than those placed into hatchery nests (67% vs. 47%, respectively). We found no impact of hyperoxia on the stage of embryonic death, hatching success, hatchling phenotype, exercise performance, or early dispersal. Our findings indicate that delayed nesting and the subsequent extension of embryonic arrest may negatively impact embryonic development and therefore the reproductive success of leatherbacks. They also indicate that incubation under hyperoxic conditions is unlikely to be a useful method to improve hatching success in this species. [ABSTRACT FROM AUTHOR]

How central and peripheral chemoreceptor drives to breathe interact in humans remains contentious. We measured the peripheral chemoreflex sensitivity to hypoxia (PChS) at various isocapnic CO2 tensions (PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$) to determine the form of the relationship between PChS and central PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$. Twenty participants (10F) completed three repetitions of modified rebreathing tests with end‐tidal PO2${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ (PETO2${P_{{\mathrm{ET}}{{\mathrm{O}}_{\mathrm{2}}}}}$) clamped at 150, 70, 60 and 45 mmHg. End‐tidal PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ (PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$), PETO2${P_{{\mathrm{ET}}{{\mathrm{O}}_{\mathrm{2}}}}}$, ventilation (V̇$\dot{V}$E) and calculated oxygen saturation (SCO2) were measured breath‐by‐breath by gas‐analyser and pneumotach. The V̇$\dot{V}$E–PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ relationship of repeat‐trials were linear‐interpolated, combined, averaged into 1 mmHg bins, and fitted with a double‐linear function (V̇$\dot{V}$ES, L min−1mmHg−1). PChS was computed at intervals of 1 mmHg of PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ as follows: the difference in V̇$\dot{V}$E between the three hypoxic profiles and the hyperoxic profile (∆V̇$\dot{V}$E) was calculated; three ∆V̇$\dot{V}$E values were plotted against corresponding SCO2; and linear regression determined PChS (Lmin−1mmHg−1%SCO2−1). These processing steps were repeated at each PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ to produce the PChS vs. isocapnic PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ relationship. These were fitted with linear and polynomial functions, and Akaike information criterion identified the best‐fit model. One‐way repeated measures analysis of variance assessed between‐condition differences. V̇$\dot{V}$ES increased (P < 0.0001) with isoxic PETO2${P_{{\mathrm{ET}}{{\mathrm{O}}_{\mathrm{2}}}}}$ from 3.7 ± 1.5 L min−1mmHg−1 at 150 mmHg to 4.4 ± 1.8, 5.0 ± 1.6 and 6.0 ± 2.2 Lmin−1mmHg−1 at 70, 60 and 45 mmHg, respectively. Mean SCO2 fell progressively (99.3 ± 0%, 93.7 ± 0.1%, 90.4 ± 0.1% and 80.5 ± 0.1%; P < 0.0001). In all individuals, PChS increased with PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$, and this relationship was best described by a linear model in 75%. Despite increasing central chemoreflex activation, PChS increased linearly with PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ indicative of an additive central–peripheral chemoreflex response. Key points: How central and peripheral chemoreceptor drives to breathe interact in humans remains contentious.We measured peripheral chemoreflex sensitivity to hypoxia (PChS) at various isocapnic carbon dioxide tensions (PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$) to determine the form of the relationship between PChS and central PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$.Participants performed three repetitions of modified rebreathing with end‐tidal PO2${P_{{{\mathrm{O}}_{\mathrm{2}}}}}$ fixed at 150, 70, 60 and 45 mmHg. PChS was computed at intervals of 1 mmHg of end‐tidal PCO2${P_{{\mathrm{C}}{{\mathrm{O}}_{\mathrm{2}}}}}$ (PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$) as follows: the difference in V̇$\dot{V}$E between the three hypoxic profiles and the hyperoxic profile (∆V̇$\dot{V}$E) was calculated; three ∆V̇$\dot{V}$E values were plotted against corresponding calculated oxygen saturation (SCO2); and linear regression determined PChS (Lmin−1mmHg−1%SCO2−1).In all individuals, PChS increased with PETCO2${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$, and this relationship was best described by a linear (rather than polynomial) model in 15 of 20.Most participants did not exhibit a hypo‐ or hyper‐additive effect of central chemoreceptors on the peripheral chemoreflex indicating that the interaction was additive. [ABSTRACT FROM AUTHOR]

The article comments on a study which examined the role of the peripheral chemoreceptors in glucose regulation and cardiovascular function in apparently healthy ndividuals and individuals diagnosed with type 2 diabetes. The researchers used hypoxic ventilatory response as an index of peripheral chemosensitivity. Study results revealed that the hypoxic ventilatory response was greater in the individuals diagnosed with type 2 diabetes.

The article discusses the ongoing HOT-ROX trial, which aims to determine the optimal concentration of oxygen to give to patients during and after surgery. The use of high-concentration oxygen has been debated, with some arguing that it reduces surgical site infections while others highlight potential complications. The trial is unique in that it includes a "usual care" group, where oxygen concentration is kept between 0.4 and 0.6. The initial results show promising group separations during surgery but less pronounced differences postoperatively. The trial will continue to analyze the impact of different oxygenation approaches on patient outcomes. [Extracted from the article]

The positive effects of combined hyperoxia and physical exercise on physiological parameters and cognitive functioning are established for normobaric laboratory contexts. Still, increased practicability exists in hyperbaric settings like underwater activities and SCUBA diving, where environmental and sport-specific factors might moderate effects. Improved cognition, reduced ventilation (V̇E), and lower blood lactate concentrations [Lac-] are highly relevant, especially during high-stress and rescue scenarios. Fifteen participants performed 3 × 8 min of continuous underwater fin-swimming at 25 % (low), 45 % (moderate), and 75 % (vigorous) heart rate reserve (HRR) in each test. Three separate test days differed solely by the inspiratory oxygen partial pressure (PIO2: 29 kPa, 56 kPa, and 140 kPa). V̇E was measured continuously, whereas breathing gas analysis, blood sampling, and Eriksen Flanker tasks for inhibitory control (100 stimuli) were performed post-exercise. Two-way ANOVAs with repeated measures on the factors PIO2 and exercise intensity analyzed physiological outcome variables and reactions times (RT) and accuracy (ACC) of inhibitory control. V̇E was significantly reduced for 140 kPa during moderate and vigorous and for 56 kPa during vigorous compared to 29 kPa. 56 kPa and 140 kPa showed no differences. [Lac-], post-exercise V̇CO2, and velocity were unaffected by PIO2. Faster RTs but lower ACC of inhibitory control were observed following exercise at 75 % HRR compared to rest, 25 %, and 45 % HRR, while PIO2 produced no effects. Underwater performance in hyperoxia presents reduced V̇E, possible by dampened chemoreceptor sensitivity, and effects on cognition that differ from laboratory results and emphasise the moderating role of sport-specific factors. Hyperoxia-induced reductions in V̇E with 56 and 140 kPa PIO2 during constant submaximal fin-swimming intensity compared to air might be prominently caused by peripheral chemoreceptor suppression. No difference between 56 and 140 kPa was detected, indicating a PIO2 threshold limiting further hyperoxic influence on V̇E. O2 supply might sufficiently cover metabolic demands of submaximal exercise with 56 kPa, while further reductions in V̇E could be observed only by severely higher PIO2. Cognitive performance by inhibitory control was unaffected by PIO2. Faster RTs but lower ACC were observed following vigorous exercise (75 % HRR) compared to rest, low, and moderate exercise. [ABSTRACT FROM AUTHOR]

Cardiac arrest (CA) and concomitant post‐CA syndrome lead to a lethal condition characterized by systemic ischemia–reperfusion injury. Oxygen (O2) supply during cardiopulmonary resuscitation (CPR) is the key to success in resuscitation, but sustained hyperoxia can produce toxic effects post CA. However, only few studies have investigated the optimal duration and dosage of O2 administration. Herein, we aimed to determine whether high concentrations of O2 at resuscitation are beneficial or harmful. After rats were resuscitated from the 10‐min asphyxia, mechanical ventilation was restarted at an FIO2 of 1.0 or 0.3. From 10 min after initiating CPR, FIO2 of both groups were maintained at 0.3. Bio‐physiological parameters including O2 consumption (VO2) and mRNA gene expression in multiple organs were evaluated. The FIO2 0.3 group decreased VO2, delayed the time required to achieve peak MAP, lowered ejection fraction (75.1 ± 3.3% and 59.0 ± 5.7% with FIO2 1.0 and 0.3, respectively; p <.05), and increased blood lactate levels (4.9 ± 0.2 mmol/L and 5.6 ± 0.2 mmol/L, respectively; p <.05) at 10 min after CPR. FIO2 0.3 group had significant increases in hypoxia‐inducible factor, inflammatory, and apoptosis‐related mRNA gene expression in the brain. Likewise, significant upregulations of hypoxia‐inducible factor and apoptosis‐related gene expression were observed in the FIO2 0.3 group in the heart and lungs. Insufficient O2 supplementation in the first 10 min of resuscitation could prolong ischemia, and may result in unfavorable biological responses 2 h after CA. Faster recovery from the impairment of O2 metabolism might contribute to the improvement of hemodynamics during the early post‐resuscitation phase; therefore, it may be reasonable to provide the maximum feasible O2 concentrations during CPR. [ABSTRACT FROM AUTHOR]

Individuals born preterm are at higher risk of cardiovascular and metabolic diseases in adulthood, through mechanisms not completely understood. White adipose tissue in humans and rodents is a dynamic endocrine organ and a critical player in the regulation of metabolic homeostasis. However, the impact of preterm birth on white adipose tissue remains unknown. Using a well‐established rodent model of preterm birth‐related conditions in which newborn rats are exposed during postnatal days 3–10 to 80% of oxygen, we evaluated the impact of transient neonatal hyperoxia on adult perirenal white adipose tissue (pWAT) and liver. We further assessed the effect of a second hit with a high‐fat high‐fructose hypercaloric diet (HFFD). We evaluated 4‐month‐old adult male rats after 2 months of HFFD. Neonatal hyperoxia led to pWAT fibrosis and macrophage infiltration without modification in body weight, pWAT weight, or adipocyte size. In animals exposed to neonatal hyperoxia vs. room air control, HFFD resulted in adipocyte hypertrophy, lipid accumulation in the liver, and increased circulating triglycerides. Overall, preterm birth‐related conditions had long‐lasting effects on the composition and morphology of pWAT, along with a higher susceptibility to the deleterious impact of a hypercaloric diet. These changes suggest a developmental pathway to long‐term metabolic risk factors observed clinically in adults born preterm through programming of white adipose tissue. [ABSTRACT FROM AUTHOR]

Hypoxia is a persistent physiological feature of many different solid tumors and a key driver of malignancy, and in recent years, it has been recognized as an important target for cancer therapy. Hypoxia occurs in the majority of solid tumors due to a poor vascular oxygen supply that is not sufficient to meet the needs of rapidly proliferating cancer cells. A hypoxic tumor microenvironment (TME) can reduce the effectiveness of other tumor therapies, such as radiotherapy, chemotherapy, and immunotherapy. In this review, we discuss the critical role of hypoxia in tumor development, including tumor metabolism, tumor immunity, and tumor angiogenesis. The treatment methods for hypoxic TME are summarized, including hypoxia‐targeted therapy and improving oxygenation by alleviating tumor hypoxia itself. Hyperoxia therapy can be used to improve tissue oxygen partial pressure and relieve tumor hypoxia. We focus on the underlying mechanisms of hyperoxia and their impact on current cancer therapies and discuss the prospects of hyperoxia therapy in cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Oxygen supply to the brain is of special importance during intracranial surgery because it may be compromised by intracranial pathology. A high arterial blood pressure (mean arterial pressure above 80 mmHg) and a high arterial oxygen tension (PaO2 above 12 kPa) is therefore often targeted in these patients, when for example intracranial pressure is increased or when a mass effect on brain tissue from a tumour is present, and it is pursued by administering vasopressors such as phenylephrine and by increasing inspiratory oxygen fraction (FiO2). However, whether these interventions increase cerebral oxygenation remains uncertain. We aimed to investigate the effect of hyperoxia and phenylephrine on brain tissue oxygen tension (PbtO2) in patients undergoing craniotomy. Methods: In this experimental study, we included 17 adult patients scheduled for elective craniotomy. After securing a stable baseline of the oxygen probe, PbtO2 was measured in white matter peripherally in the surgical field during general anaesthesia. Primary comparisons were PbtO2 before versus after an increase in FiO2 from 0.30 to 0.80 as well as before versus after a bolus dose of phenylephrine (0.1–0.2 mg depending on patient haemodynamics). Data were analysed with the Wilcoxon signed rank test. Results: We obtained complete data sets in 11 patients undergoing the FiO2 increase and six patients receiving the phenylephrine bolus. PbtO2 was 22 (median; 5%–95% range, 4.6–54) mmHg during 30% oxygen, 68 (8.4–99) mmHg during 80% oxygen (p =.004 compared to 30% oxygen), 21 (4.5–81) mmHg before phenylephrine, and 19 (4.2–56) mmHg after phenylephrine (p =.56 compared to before phenylephrine). Conclusion: In patients undergoing craniotomy under general anaesthesia, brain tissue oxygen tension increased with a high inspiratory oxygen fraction but remained unchanged after a bolus dose of phenylephrine. [ABSTRACT FROM AUTHOR]

Experimental hyperoxia has been shown to enhance the maximum oxygen uptake capacity of fishes under acute conditions, potentially offering an avenue to test prominent physiological hypotheses attempting to explain impacts of climate warming on fish populations (e.g., gill‐oxygen limitation driving declines in fish size). Such benefits of experimental hyperoxia must persist under chronic conditions if it is to provide a valid manipulation to test the relevant hypotheses, yet the long‐term benefits of experimental hyperoxia to oxygen uptake capacity have not been examined. Here, the authors measured aerobic metabolic performance of Galaxias maculatus upon acute exposure to hyperoxia (150% air saturation) and after 5 months of acclimation, at both 15°C and 20°C. Acute hyperoxia elevated aerobic scope by 74%–94% relative to normoxic controls, and an elevation of 58%–73% persisted after 5 months of hyperoxia acclimation. When hyperoxia‐acclimated fish were acutely transitioned back to normoxia, they maintained superior aerobic performance compared with normoxic controls, suggesting an acclimation of the underlying metabolic structures/processes. In demonstrating the long‐term benefits of experimental hyperoxia on the aerobic performance of a fish, the authors encourage the use of such approaches to disentangle the role of oxygen in driving the responses of fish populations to climate warming. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?We assessed the test–retest variability of respiratory chemoreflex characterization by Duffin's modified rebreathing method and explored whether signal averaging of repeated trials improves confidence in parameter estimation.What is the main finding and its importance?Modified rebreathing is a reproducible method to characterize responses of central and peripheral respiratory chemoreflexes. Signal averaging of multiple repeated tests minimizes within‐ and between‐test variability, improves the confidence of chemoreflex characterization and reduces the minimal change in parameters required to establish an effect. Future experiments that apply this method might benefit from signal averaging to improve its discriminatory effect. We assessed the test–retest variability of central and peripheral respiratory chemoreflex characterization by Duffin's modified rebreathing method and explored whether signal averaging of repeated trials improves confidence in parameter estimation. Over four laboratory visits, 13 participants (mean ± SD age, 25 ± 5 years) performed six repetitions of modified rebreathing in isoxic–hypoxic conditions [end‐tidal PO2${P_{{{\rm{O}}_{\rm{2}}}}}$ (PET,O2${P_{{\rm{ET,}}{{\rm{O}}_{\rm{2}}}}}$) = 50 mmHg] and isoxic–hyperoxic conditions (PET,O2${P_{{\rm{ET,}}{{\rm{O}}_{\rm{2}}}}}$ = 150 mmHg). End‐tidal PCO2${P_{{\rm{C}}{{\rm{O}}_{\rm{2}}}}}$ (PET,CO2${P_{{\rm{ET,C}}{{\rm{O}}_{\rm{2}}}}}$), PET,O2${P_{{\rm{ET,}}{{\rm{O}}_{\rm{2}}}}}$ and minute ventilation (V̇$\dot {\rm V}$E) were measured breath‐by‐breath, by gas analyser and pneumotachograph. The V̇$\dot {\rm V}$E versus PET,CO2${P_{{\rm{ET,C}}{{\rm{O}}_{\rm{2}}}}}$ relationships were fitted with a piecewise model to estimate the ventilatory recruitment threshold (VRT) and the slope above the VRT (V̇$\dot {\rm V}$ES). Breath‐by‐breath data from the three within‐ and between‐day trials were averaged using two approaches [simple average (fit then average) and ensemble average (average then fit)] and compared with a single‐trial fit. Variability was assessed by intraclass correlation (ICC) and coefficient of variance (CV), and the minimal detectable change was computed for each approach using two independent sets of three trials. Within days, the VRT and V̇$\dot {\rm V}$ES exhibited excellent test–retest variability in both hyperoxic conditions (VRT: ICC = 0.965, CV = 2.3%; V̇$\dot {\rm V}$ES: ICC = 0.932, CV = 15.5%) and hypoxic conditions (VRT: ICC = 0.970, CV = 2.9%; V̇$\dot {\rm V}$ES: ICC = 0.891, CV = 17.2%). Between‐day reproducibility was also excellent (hyperoxia, VRT: ICC = 0.930, CV = 2.2%; V̇$\dot {\rm V}$ES: ICC = 0.918, CV = 14.2%; and hypoxia, VRT: ICC = 0.940, CV = 3.0%; V̇$\dot {\rm V}$ES: ICC = 0.880, CV = 18.1%). Compared with a single‐trial fit, there were no differences in VRT or V̇$\dot {\rm V}$ES using the simple average or ensemble average approaches; however, ensemble averaging reduced the minimal detectable change for V̇$\dot {\rm V}$ES from 2.95 to 1.39 L min−1 mmHg−1 (hyperoxia) and from 3.64 to 1.82 L min−1 mmHg−1 (hypoxia). Single trials of modified rebreathing are reproducible; however, signal averaging of repeated trials improves confidence in parameter estimation. [ABSTRACT FROM AUTHOR]

Background: Multiple studies have investigated the association between hyperoxaemia following cardiac arrest (CA) and unfavourable outcomes; however, they have yielded inconsistent results. Most previous studies quantified oxygen exposure without considering its timing or duration. We investigated the relationship between unfavourable outcomes and supranormal arterial oxygen tension (PaO2), commonly defined as PaO2 > 100 mmHg, at specific time intervals within 24 h following CA. Methods: This retrospective observational study included 838 adult non‐traumatic patients with CA. The first 24 h following CA were divided into four 6‐h time intervals, and the first 6‐h period was further divided into three 2‐h segments. Multivariable logistic regression analyses were conducted to assess associations of the highest PaO2 and time‐weighted average PaO2 (TWA‐PaO2) values at each time interval with unfavourable outcomes at hospital discharge (cerebral performance categories 3–5). Results: The highest PaO2 (p =.028) and TWA‐PaO2 (p =.022) values during the 0–6‐h time interval were significantly associated with unfavourable outcomes, whereas those at time intervals beyond 6 h were not. The association was the strongest at supranormal PaO2 values within the 0–2‐h time interval, becoming significant at PaO2 values ≥ 150 mmHg. During the first 6 h, longer time spent at ≥150 mmHg of PaO2 was associated with an increased risk of unfavourable outcomes (p =.038). The results were consistent across several sensitivity analyses. Conclusion: Supranormal PaO2 during but not after the first 6 h following cardiac arrest was independently associated with unfavourable outcomes. [ABSTRACT FROM AUTHOR]

Objective: In adult brain tissue, oxygen levels typically remain in the normoxic zone, but status epilepticus results in hyperoxia, whereas brief self‐terminating seizures lead to postictal hypoxia. The dynamic changes in oxygen levels and the underlying mechanisms are unknown in juveniles with febrile seizures. Methods: Eight‐day‐old female and male rat pups were implanted with an electrode and oxygen‐sensing optode in the hippocampus and then received once daily injections of lipopolysaccharide for 4 days to induce an immune response. Local partial pressure of oxygen (pO2) and local field potentials were recorded before, during, and after a heat‐induced febrile seizure. Separate groups of pups received injections of vehicle or drugs targeting cyclooxygenase (COX)‐1, COX‐2, L‐type calcium channels (LTCCs), and cannabinoid receptor type 1 (CB1) and transient receptor potential vanilloid‐1 (TRPV1) receptors prior to febrile seizure induction to determine pO2 mechanisms. Following febrile seizures, a subset of pups were raised to young adulthood and then tested for learning impairments using the novel object recognition task. Results: Febrile seizures resulted in predictable oxygen dynamics that were related to behavioral seizures and epileptiform activity. During a behavioral seizure, pO2 rapidly increased, rapidly decreased, and then returned to near baseline. When the behavioral seizure terminated, oxygen levels climbed into the hyperoxic zone during a time of prolonged epileptiform activity. When epileptiform activity terminated, oxygen levels slowly returned to baseline. A COX‐1 antagonist prevented hyperoxia, whereas a COX‐2 antagonist did not. An LTCC antagonist exacerbated hyperoxia. Boosting levels of an endocannabinoid also exacerbated hyperoxia, whereas blocking CB1 receptors and TRPV1 receptors reduced hyperoxia. Inhibiting TRPV1 receptors during a febrile seizure prevented learning deficits in young adult female rats. Significance: Brain oxygenation during and following a febrile seizure has a distinct pattern and multiple mechanisms. Brain oxygen dynamics may be an important consideration in the development of treatments for febrile seizures. [ABSTRACT FROM AUTHOR]

Purpose: Inducing hyperoxia in tissues is common practice in several areas of research, including oxygen‐enhanced MRI (OE‐MRI), which attempts to use the resulting signal changes to detect regions of tumor hypoxia or pulmonary disease. The linear relationship between PO2 and R1 has been reproduced in phantom solutions and body fluids such as vitreous fluid; however, in tissue and blood experiments, factors such as changes in deoxyhemoglobin levels can also affect the ΔR1. Theory and Methods: This manuscript proposes a three‐compartment model for estimating the hyperoxia‐induced changes in R1 of tissues depending on B0, SO2, blood volume, hematocrit, oxygen extraction fraction, and changes in blood and tissue PO2. The model contains two blood compartments (arterial and venous) and a tissue compartment. This model has been designed to be easy for researchers to tailor to their tissue of interest by substituting their preferred model for tissue oxygen diffusion and consumption. A specific application of the model is demonstrated by calculating the resulting ΔR1 expected in healthy, hypoxic and necrotic tumor tissues. In addition, the effect of sex‐based hematocrit differences on ΔR1 is assessed. Results: The ΔR1 values predicted by the model are consistent with reported literature OE‐MRI results: with larger positive changes in the vascular periphery than hypoxic and necrotic regions. The observed sex‐based differences in ΔR1 agree with findings by Kindvall et al. suggesting that differences in hematocrit levels may sometimes be a confounding factor in ΔR1. Conclusion: This model can be used to estimate the expected tissue ΔR1 in oxygen‐enhanced MRI experiments. [ABSTRACT FROM AUTHOR]

Background: To reduce risk for intermittent hypoxia a high fraction of inspired oxygen is routinely used during anesthesia induction. This differs from the cautious dosing of oxygen during neonatal resuscitation and intensive care and may result in significant hyperoxia. Aim: In a randomized controlled trial, we evaluated oxygenation during general anesthesia with a low (23%) vs a high (80% during induction and recovery, and 40% during maintenance) fraction of inspired oxygen, in newborn infants undergoing surgery. Method: Thirty‐five newborn infants with postconceptional age of 35–44 weeks were included (17 infants in low and 18 in high oxygen group). Oxygenation was monitored by transcutaneous partial pressure of oxygen, pulse oximetry, and cerebral oxygenation. Predefined SpO2 safety targets dictated when to increase inspired oxygen. Results: At start of anesthesia, oxygenation was similar in both groups. Throughout anesthesia, the high oxygen group displayed significant hyperoxia with higher (difference−20.3 kPa, 95% confidence interval (CI)—28.4 to 12.2, p <.001) transcutaneous partial pressure of oxygen values than the low oxygen group. While SpO2 in the low oxygen group was lower (difference − 5.8%, 95% CI –9.3 to –2.4, p <.001) during anesthesia, none of the infants spent enough time below SpO2 safety targets to mandate supplemental oxygen, and cerebral oxygenation was within the normal range and not statistically different between the groups. Analysis of the oxidative stress biomarker urinary F2‐Isoprostane revealed no differences between the low and high oxygen group. Conclusion: We conclude that in healthy newborn infants, use of low oxygen during general anesthesia was feasible, while the prevailing practice of using high levels of inspired oxygen resulted in significant hyperoxia. The trade‐off between careful dosing of oxygen and risks of hypo‐ and hyperoxia in neonatal anesthesia should be further examined. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the response of the superficial and deep capillary plexuses to hyperoxia and hypoxia using optical coherence tomography angiography (OCT‐A) and retinal vessel analyzer. Methods: Twenty‐four healthy volunteers participated in this randomized, double‐masked, cross‐over study. For each subject, two study days were scheduled: on one study day, hyperoxia was induced by breathing 100% oxygen whereas on the other study day, hypoxia was induced by breathing a mixture of 88% nitrogen and 12% oxygen. Perfusion density was calculated in the superficial vascular plexus (SVP) and the deep capillary plexus (DCP), using OCT‐A before (normal breathing) and during breathing of the gas mixtures. Retinal vessel calibres in major retinal vessels were measured using a dynamic vessel analyzer. Results: During 100% oxygen breathing, a significant decrease in DCP perfusion density from 41.7 ± 2.4 a.u to 35.6 ± 3.1 a.u. (p < 0.001) was observed, which was accompanied by a significant decrease in vessel diameters in major retinal arteries and veins (p < 0.001 each). No significant change in perfusion density in the SVP occurred (p = 0.33). In contrast, during hypoxia, perfusion density in the SVP significantly increased from 34.4 ± 3.0 a.u. to 37.1 ± 2.2 a.u. (p < 0.001), while it remained stable in the DCP (p = 0.25). A significant increase in retinal vessel diameters was found (p < 0.01). Systemic oxygen saturation correlated negatively with perfusion density in the SVP and the DCP and retinal vessel diameters (p < 0.005 each). Conclusion: Our results show that systemic hyperoxia induces a significant decrease in vessel density in the DCP, while hypoxia leads to increased vessel density limited to the SVP. These results indicate that the retinal circulation shows the ability to adapt its blood flow to metabolic changes with high local resolution dependent on the capillary plexus. [ABSTRACT FROM AUTHOR]

Diabetic calcific tendinopathy is the leading cause of chronic pain, mobility restriction, and tendon rupture in patients with diabetes. Tendon stem/progenitor cells (TSPCs) have been implicated in the development of diabetic calcified tendinopathy, but the molecular mechanisms remain unclear. This study found that diabetic tendons have a hyperoxic environment, characterized by increased oxygen delivery channels and carriers. In hyperoxic environment, TSPCs showed enhanced osteogenic differentiation and increased levels of reactive oxygen species (ROS). Additionally, hypoxia-inducible factor-1a (HIF-1a), a protein involved in regulating cellular responses to hyperoxia, was decreased in TSPCs by the ubiquitin-proteasome system. By intervening with antioxidant N-acetyl-L-cysteine (NAC) and overexpressing HIF-1a, we discovered that blocking the ROS/HIF-1a signalling axis significantly inhibited the osteogenic differentiation ability of TSPCs. Animal experiments further confirmed that hyperoxic environment could cause calcification in the Achilles tendon tissue of rats, while NAC intervention prevented calcification. These findings demonstrate that hyperoxia in diabetic tendons promotes osteogenic differentiation of TSPCs through the ROS/HIF-1a signalling axis. This study provides a new theoretical basis and research target for preventing and treating diabetic calcified tendinopathy., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

The adverse factors impacting the intestinal microbiota of newborns remain to be elucidated. We put forward a hypothesis that hyperoxia in combination with rituximab exhibits a synergistic effect that interferes with neonatal intestinal microbiota. Six C57BL/6J mice, aged 12 weeks and pregnant 18 days, were purchased. Their pups were breastfed and raised under a 75% oxygen or conventional environment. Low‐ (20 mg/kg) and high‐dose (40 mg/kg) rituximab were intraperitoneally administered. Fecal genomic DNA was extracted and sequenced by a 16S rRNA platform. Severe intestinal dysbiosis in newborns were observed, whereas mild dysbiosis was caused by inducing hyperoxia alone, confirming the synergistic interference of the combination of hyperoxia and B‐cell antagonist (rituximab) in neonatal intestinal microbiota disruption. Slight dysbiosis was observed in the intestinal microbiota of dams, indicating their much robust ability to confront hyperoxic conditions. The abundance of Akkermansia muciniphila was significantly and extensively altered in both pups and dams after being subjecting them to hyperoxic conditions with or without rituximab administration. In conclusion, this work demonstrated that the synergistic effect of hyperoxia and rituximab led to severe intestinal dysbiosis in newborns. More studies are recommended to explore the precise regulatory mode between hyperoxia and rituximab in intestinal microbiota. [ABSTRACT FROM AUTHOR]

Hyperoxia, is often used in preterm supportive care, leading to high oxygen exposure in neonates. Coenzyme Q10 (CoQ10) is a free radical scavenger that has been studied in older children but never be investigated for its role in preterm care. We hypothesize that the administration of exogenous CoQ10 would raise serum concentrations of CoQ10 and mitigate the adverse effects of hyperoxia on the organs by reducing oxygen‐free radicals and inflammation. The aim of this study was to evaluate the effects of oxidative stress, inflammatory response, and survival in neonatal rats after CoQ10 treatment. Neonatal rats delivered from four pregnant Wistar rats were randomly divided into four groups: (a) control, (b) CoQ10, (c) hyperoxia (O2 group), and (d) treatment (CoQ10 + O2) groups. The dose of CoQ10 injected was 30 mg/kg. The CoQ9, CoQ10, cytokines, oxidative stress, and antioxidant enzyme activity were measured. Tissue samples were histologically examined and mortality was monitored for 16 days. The level of CoQ9 significantly increased in the liver, kidney, and plasma, while the level of CoQ10 significantly increased in most organ tissues in the CoQ10 + O2 group. Additionally, CoQ10 decrease oxidative stress in the liver, increase antioxidant enzyme activity in the heart, kidney, and brain, and reverse an inclined level of hematopoietic growth factors. However, CoQ10 had no effect on inflammation, organ damage, or mortality. Therefore, the use of CoQ10 in potential adjuvant therapy for neonatal hyperoxia requires further research. [ABSTRACT FROM AUTHOR]

Background: Under normal physiological conditions, the spin–lattice relaxation rate (R1) in blood is influenced by many factors, including hematocrit, field strength, and the paramagnetic effects of deoxyhemoglobin and dissolved oxygen. In addition, techniques such as oxygen‐enhanced magnetic resonance imaging (MRI) require high fractions of inspired oxygen to induce hyperoxia, which complicates the R1 signal further. A quantitative model relating total blood oxygen content to R1 could help explain these effects. Purpose: To propose and assess a general model to estimate the R1 of blood, accounting for hematocrit, SO2, PO2, and B0 under both normal physiological and hyperoxic conditions. Study Type: Mathematical modeling. Population: One hundred and twenty‐six published values of R1 from phantoms and animal models. Field Strength/Sequence: 5–8.45 T. Assessment: We propose a two‐compartment nonlinear model to calculate R1 as a function of hematocrit, PO2, and B0. The Akaike Information Criterion (AIC) was used to select the best‐performing model with the fewest parameters. A previous model of R1 as a function of hematocrit, SO2, and B0 has been proposed by Hales et al, and our work builds upon this work to make the model applicable under hyperoxic conditions (SO2 > 0.99). Models were assessed using the AIC, mean squared error (MSE), coefficient of determination (R2), and Bland–Altman analysis. The effect of volume fraction constants WRBC and Wplasma was assessed by the SD of resulting R1. The range of the model was determined by the maximum and minimum B0, hematocrit, SO2, and PO2 of the literature data points. Statistical Tests: Bland–Altman, AIC, MSE, coefficient of determination (R2), SD. Results: The model estimates agreed well with the literature values of R1 of blood (R2 = 0.93, MSE = 0.0013 s−2), and its performance was consistent across the range of parameters: B0 = 1.5–8.45 T, SO2 = 0.40–1, PO2 = 30–700 mmHg. Data Conclusion: Using the results from this model, we have quantified and explained the contradictory decrease in R1 reported in oxygen‐enhanced MRI and oxygen‐delivery experiments. Level of Evidence: 3 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

The article presents the discussion on guidelines for the administration of oxygen in hypoxaemic patients with Covid-19. Topics include having sepsis, myocardial infarction, acute respiratory distress syndrome (ARDS), and trauma; and complicated by development of endotheliitis and vascular damage, disrupted vasoregulation, loss of lung perfusion regulation, and enhanced hypercoagulability and thrombogenesis.

Purpose: Retinal oximetry measures oxygen saturation in retinal vessels. With the introduction of a mobile handheld prototype oximeter, this technique will become available for a broader patient population including bedridden patients and newborn babies. The objective is to determine the sensitivity of this handheld oximeter in room air and during isocapnic hyperoxia. A comparison is made between the handheld oximeter and the Oxymap T1. Methods: Thirteen young healthy subjects with a mean age of 25 ± 2 years were recruited at the Leiden University Medical Center. Retinal oximetry images were acquired during normoxia and during isocapnic hyperoxia for both the prototype oximeter and the OxymapT1. Isocapnic hyperoxia was induced with the dynamic end‐tidal forcing technique. For both oximeters, the oxygen saturation and vessel width were measured with Oxymap Analyzer software. The hyperoxic state was verified with blood gas analysis. Results: The mean oxygen saturation measured with the handheld oximeter in arterioles was 91.3% ± 3.9% during normoxia and 94.6% ± 3.9% during hyperoxia (p = 0.001). Oxygen saturation in venules was 56.3% ± 9.8% during normoxia and 82.2 ± 7.4% during hyperoxia (p < 0.001). For the Oxymap T1, the mean oxygen saturation for arterioles was 94.0% ± 2.6% during normoxia and 95.4%±3.2% during hyperoxia (p = 0.004). For the venules, the oxygen saturation was during normoxia 58.9%±3.2% and 84.3 ± 4.0% during hyperoxia (p < 0.001). Conclusion: The handheld retinal oximeter is sensitive to the changes in inhaled oxygen concentration. A small increase in oxygen saturation was measured in the arterioles and a larger increase in the venules. The handheld oximeter gives similar values as the 'gold standard' Oxymap T1 oximeter. [ABSTRACT FROM AUTHOR]

Hypoxia and hypoxemia are two different entities. Correcting hypoxemia without hypoxia tends to have disastrous effects and delays lung healing. In this study, we share a case of an elderly man with moderate COVID‐19 who never received any form of supplemental oxygen as compared to other patients with similar presentation. [ABSTRACT FROM AUTHOR]

Aim: To explore the current literature on prenatal inflammation‐associated risk factors for retinopathy of prematurity (ROP). Methods: Subjective summary of selected experimental and epidemiological publications that support the authors' central hypothesis that the aetiology of ROP begins before birth. Results: Based on current evidence we suggest that, contrary to current aetiological models, the process of ROP development begins with a prephase in utero. This beginning is likely initiated by inflammatory responses that are associated with intrauterine infection. Conclusion: We propose a novel aetio‐pathogenetic model of ROP and suggest that the effects of postnatal exposure to inflammatory stressors (resulting from infection or hyperoxia or both) as well as those of other pre‐ and postnatal contributors to the complex pathogenesis of ROP might be modified by the prenatal phase of the disease. [ABSTRACT FROM AUTHOR]

Key points: The proposed mechanism for the increased ventilation in response to hyperoxia includes a reduced brain CO2–[H+] washout‐induced central chemoreceptor stimulation that results from a decrease in cerebral perfusion and the weakening of the CO2 affinity for haemoglobin.Nonetheless, hyperoxia also results in excessive brain reactive oxygen species (ROS) formation/accumulation, which hypothetically increases central respiratory drive and causes hyperventilation.We then quantified ventilation, cerebral perfusion/metabolism, arterial/internal jugular vein blood gases and oxidant/antioxidant biomarkers in response to hyperoxia during intravenous infusion of saline or ascorbic acid to determine whether excessive ROS production/accumulation contributes to the hyperoxia‐induced hyperventilation in humans.Ascorbic acid infusion augmented the antioxidant defence levels, blunted ROS production/accumulation and minimized both the reduction in cerebral perfusion and the increase in ventilation observed during saline infusion.Hyperoxic hyperventilation seems to be mediated by central chemoreceptor stimulation provoked by the interaction between an excessive ROS production/accumulation and reduced brain CO2–[H+] washout. The hypothetical mechanism for the increase in ventilation (V̇E) in response to hyperoxia (HX) includes central chemoreceptor stimulation via reduced CO2–[H+] washout. Nonetheless, hyperoxia disturbs redox homeostasis and raises the hypothesis that excessive brain reactive oxygen species (ROS) production/accumulation may increase the sensitivity to CO2 or even solely activate the central chemoreceptors, resulting in hyperventilation. To determine the mechanism behind the HX‐evoked increase in V̇E, 10 healthy men (24 ± 4 years) underwent 10 min trials of HX under saline and ascorbic acid infusion. V̇E, arterial and right internal right jugular vein (ijv) partial pressure for oxygen (PO2) and CO2 (PCO2), pH, oxidant (8‐isoprostane) and antioxidant (ascorbic acid) markers, as well as cerebral blood flow (CBF) (Duplex ultrasonography), were quantified at each hyperoxic trial. HX evoked an increase in arterial partial pressure for oxygen, followed by a hyperventilatory response, a reduction in CBF, an increase in arterial 8‐isoprostane, and unchanged PijvCO2 and ijv pH. Intravenous ascorbic acid infusion augmented the arterial antioxidant marker, blunted the increase in arterial 8‐isoprostane and attenuated both the reduction in CBF and the HX‐induced hyperventilation. Although ascorbic acid infusion resulted in a slight increase in PijvCO2 and a substantial decrease in ijv pH, when compared with the saline bout, HX evoked a similar reduction and a paired increase in the trans‐cerebral exchanges for PCO2 and pH, respectively. These findings indicate that the poikilocapnic hyperoxic hyperventilation is likely mediated via the interaction of the acidic brain interstitial fluid and an increase in central chemoreceptor sensitivity to CO2, which, in turn, seems to be evoked by the excessive ROS production/accumulation. Key points: The proposed mechanism for the increased ventilation in response to hyperoxia includes a reduced brain CO2–[H+] washout‐induced central chemoreceptor stimulation that results from a decrease in cerebral perfusion and the weakening of the CO2 affinity for haemoglobin.Nonetheless, hyperoxia also results in excessive brain reactive oxygen species (ROS) formation/accumulation, which hypothetically increases central respiratory drive and causes hyperventilation.We then quantified ventilation, cerebral perfusion/metabolism, arterial/internal jugular vein blood gases and oxidant/antioxidant biomarkers in response to hyperoxia during intravenous infusion of saline or ascorbic acid to determine whether excessive ROS production/accumulation contributes to the hyperoxia‐induced hyperventilation in humans.Ascorbic acid infusion augmented the antioxidant defence levels, blunted ROS production/accumulation and minimized both the reduction in cerebral perfusion and the increase in ventilation observed during saline infusion.Hyperoxic hyperventilation seems to be mediated by central chemoreceptor stimulation provoked by the interaction between an excessive ROS production/accumulation and reduced brain CO2–[H+] washout. [ABSTRACT FROM AUTHOR]

Neutrophils are the most abundant circulating white blood cells and are the central players of the innate immune response. During their lifecycle, neutrophils mainly evolve under low oxygen conditions (0.1–4% O2), to which they are well adapted. Neutrophils are atypical cells since they are highly glycolytic and susceptible to oxygen exposure, which induces their activation and death through mechanisms that remain currently elusive. Nevertheless, nearly all studies conducted on neutrophils are carried out under atmospheric oxygen (21%), corresponding to hyperoxia. Here, we investigated the impact of hyperoxia during neutrophil purification and culture on neutrophil viability, activation and cytosolic protein content. We demonstrate that neutrophil hyper‐activation (CD62L shedding) is induced during culture under hyperoxic conditions (24 h), compared with neutrophils cultured under anoxic conditions. Spontaneous neutrophil extracellular trap (NET) formation is observed when neutrophils face hyperoxia during purification or culture. In addition, we show that maintaining neutrophils in autologous plasma is the preferred strategy to maintain their basal state. Our results show that manipulating neutrophils under hyperoxic conditions leads to the loss of 57 cytosolic proteins during purification, while it does not lead to an immediate impact on neutrophil activation (CD11bhigh, CD54high, CD62Lneg) or viability (DAPI+). We identified two clusters of proteins belonging to cholesterol metabolism and to the complement and coagulation cascade pathways, which are highly susceptible to neutrophil oxygen exposure during neutrophil purification. In conclusion, protecting neutrophil from oxygen during their purification and culture is recommended to avoid activation and to prevent the alteration of cytosolic protein composition. [ABSTRACT FROM AUTHOR]

Clinical reports suggest a high incidence of ICU mortality with the use of hyperoxia during mechanical ventilation in patients. Our laboratory is pioneer in studying effect of hyperoxia on cardiac pathophysiology. In this study for the first time, we are reporting the sequence of cardiac pathophysiological events in mice under hyperoxic conditions in time‐dependent manner. C57BL/6J male mice, aged 8–10 weeks, were treated with either normal air or >90% oxygen for 24, 48, and 72 h. Following normal air or hyperoxia treatment, physical, biochemical, functional, electrical, and molecular parameters were analyzed. Our data showed that significant reduction of body weight observed as early as 24 h hyperoxia treatment, whereas, no significant changes in heart weight until 72 h. Although we do not see any fibrosis in these hearts, but observed significant increase in cardiomyocyte size with hyperoxia treatment in time‐dependent manner. Our data also demonstrated that arrhythmias were present in mice at 24 h hyperoxia, and worsened comparatively after 48 and 72 h. Echocardiogram data confirmed cardiac dysfunction in time‐dependent manner. Dysregulation of ion channels such as Kv4.2 and KChIP2; and serum cardiac markers confirmed that hyperoxia‐induced effects worsen with each time point. From these observations, it is evident that electrical remodeling precedes structural remodeling, both of which gets worse with length of hyperoxia exposure, therefore shorter periods of hyperoxia exposure is always beneficial for better outcome in ICU/critical care units. [ABSTRACT FROM AUTHOR]

Background and Purpose: Bronchopulmonary dysplasia (BPD) is the most prevalent chronic paediatric lung disease and is linked to the development of chronic obstructive pulmonary disease. MicroRNA-based regulation of type II alveolar epithelial cell (T2AEC) proliferation and apoptosis is an important factor in the pathogenesis of BPD and warrants further investigation.Experimental Approach: Two murine models of hyperoxic lung injury (with or without miR-342-5p or Sprouty-related, EVH1 domain-containing protein 3 [Spred3] modulation) were employed: a hyperoxia-induced acute lung injury model (100% O2 on postnatal days 1-7) and the BPD model (100% O2 on postnatal days 1-4, followed by room air for 10 days). Tracheal aspirate pellets from healthy control and moderate/severe BPD neonates were randomly selected for clinical miR-342-5p analysis.Key Results: Hyperoxia decreased miR-342-5p levels in primary T2AECs, MLE12 cells and neonatal mouse lungs. Transgenic miR-342 overexpression in neonatal mice ameliorated survival rates and improved the BPD phenotype and BPD-associated pulmonary arterial hypertension (PAH). T2AEC-specific miR-342 transgenic overexpression, as well as miR-342-5p mimic therapy, also ameliorated the BPD phenotype and associated PAH. miR-342-5p targets the 3'UTR of the Raf1 regulator Spred3, inhibiting Spred3 expression. Treatment with recombinant Spred3 exacerbated the BPD phenotype and associated PAH. Notably, miR-342-5p inhibition under room air conditions did not mimic the BPD phenotype. Moderate/severe BPD tracheal aspirate pellets exhibited decreased miR-342-5p levels relative to healthy control pellets.Conclusion and Implications: These findings suggest that miR-342-5p mimic therapy may show promise in the treatment or prevention of BPD. [ABSTRACT FROM AUTHOR]

Supplemental oxygen and mechanical ventilation commonly used in premature infants may lead to chronic lung disease of prematurity, which is characterized by arrested alveolar development and dysmorphic vascular development. Hyperoxia is also known to dysregulate p53, senescence, and metabolism. However, whether these changes in p53, senescence, and metabolism are intertwined in response to hyperoxia is still unknown. Given that the lung epithelium is the first cell to encounter ambient oxygen during a hyperoxic exposure, we used mouse lung epithelial cells (MLE‐12), surfactant protein expressing type II cells, to explore whether hyperoxic exposure alters senescence and glycolysis. We measured glycolytic rate using a Seahorse Bioanalyzer assay and senescence using a senescence‐associated β galactosidase activity assay with X‐gal and C12FDG as substrates. We found that hyperoxic exposure caused senescence and increased glycolysis as well as reduced proliferation. This was associated with increased double stranded DNA damage, p53 phosphorylation and nuclear localization. Furthermore, hyperoxia‐induced senescence was p53‐dependent, but not pRB‐dependent, as shown in p53KO and pRBKO cell lines. Despite the inhibitory effects of p53 on glycolysis, we observed that glycolysis was upregulated in hyperoxia‐exposed MLE‐12 cells. This was attributable to a subpopulation of highly glycolytic senescent cells detected by C12FDG sorting. Nevertheless, inhibition of glycolysis did not prevent hyperoxia‐induced senescence. Therapeutic strategies modulating p53 and glycolysis may be useful to mitigate the detrimental consequences of hyperoxia in the neonatal lung. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of this study?The beneficial effects of supplemental oxygen in patients with acute myocardial infarction are still uncertain: what are the effects of ischaemia–reperfusion injury during hyperoxia and normoxia in mature rats with and without cardiovascular risk factors?What is the main finding and its importance?Despite elevated baseline oxidative stress in rodents with cardiovascular risk factors, hyperoxic reperfusion limited myocardial necrosis and anti/pro‐oxidant imbalance in spontaneously hypertensive and Zucker rats. In contrast, this effect was exacerbated in healthy Wistar rats. These results suggest that oxygen supplementation may not be harmful in patients with acute myocardial injury. Recent studies on O2 supplementation in acute coronary syndrome patients are equivocal. We tested the hypothesis that oxidative stress is increased in rodents with cardiovascular risk factors and enhances ischaemia–reperfusion injury in the presence of hyperoxia. A total of 43 Wistar rats (WR), 30 spontaneously hypertensive rats (SHR) and 33 obese Zucker rats (ZR) were randomized in a sham procedure (one‐third) or underwent a left anterior descending ligation of the coronary artery for 60 min (two‐thirds). This was followed by 3 h of reperfusion while animals were randomized either in a hyperoxic (HR) or a normoxic reperfusion (NR) group. Myocardial infarction size and oxidative stress biomarkers (myeloperoxidase (MPO), malondialdehyde and total free thiols) were assessed in blood samples. Baseline troponin T was higher in SHR and ZR than in WR (both P < 0.001). Baseline total MPO was elevated in ZR in comparison to SHR and WR (both P < 0.001). SHR had lower thiol concentration compared to WR and ZR (P < 0.000001). HR was associated with a lower troponin T rise in SHR and ZR than in NR (both P < 0.001), while the reverse occurred in WR (P < 0.001). In SHR, HR limited total MPO increase as compared to NR (P = 0.0056) and the opposite effect was observed with total MPO in WR (P = 0.013). NR was associated with a drastic reduction of total thiols as compared to HR both in SHR and in ZR (both P < 0.001). Despite a heightened baseline oxidative stress level, HR limited myocardial necrosis and anti/pro‐oxidant imbalance in SHR and ZR whereas this effect was exacerbated in healthy WR. [ABSTRACT FROM AUTHOR]

Abnormal development of immature retinal vascular structure in preterm infants under the condition of hyperoxia is the primary cause of retinopathy of prematurity (ROP), which has become the leading cause of blindness in children. Retinal ganglion cells (RGCs) play a critical role in the normal growth of retinal vessels. Previous studies have indicated that estrogen can alleviate retinal lesions in the ROP animal model by inhibiting reactive oxygen species, which is associated with endoplasmic reticulum (ER) stress. This study aimed to investigate the protecting effect of G‐protein coupled estrogen receptor (GPER), one of the estrogen receptors distributed in ER, on RGCs in the early stage of ROP and its relationship with ER stress. We found that GPER was widely expressed in primary cultured murine RGCs. GPER activation by its agonist G‐1 increased cell vitality and decreased apoptosis and autophagy of RGCs under hyperoxia. GPER activation by G‐1 decreased the expressions of the ER stress proteins, including inositol‐requiring kinase/endonuclease 1α, pancreatic ER stress kinase, and cleaved activating transcription factor 6 in ER of RGCs under hyperoxia. GPER activation decreased IP3R activity and increased Ca2+ concentration in ER of RGCs under hyperoxia. In addition, GPER antagonist (G‐15) reversed all these effects of the GPER agonist mentioned above. This study suggested that GPER activation can protect the survival of RGCs in the early stage of ROP via reducing ER stress in RGCs under the condition of hyperoxia. [ABSTRACT FROM AUTHOR]

Hyperoxia occurs when water oxygen (O2) levels exceed normal atmospheric pressure (i.e., >100% air saturation). Fish can experience hyperoxia in shallow environments due to photosynthesis or in aquaculture through O2 supplementation. This review provides a comprehensive synthesis of the effects of hyperoxia on fish, spanning influences on cardiorespiratory function, acid‐base balance, oxidative stress and whole animal performance (e.g., thermal tolerance and growth). Fish hypoventilate in hyperoxia, but arterial and venous blood oxygenation increases in spite of reduced convection. Persistently high levels of blood oxygenation in hyperoxia do not commonly result in reduced blood O2 carrying capacity, but assessments in undisturbed fish are required to clarify this. Hypoventilation also causes the retention of carbon dioxide, hence respiratory acidosis. Another consequence of hyperoxia is increased levels of oxidative stress and concomitant changes to antioxidant defence systems. Despite these changes, however, the bulk of evidence shows no effect of hyperoxia on growth. Hyperoxia does impact the aerobic metabolic rate of fish with either no effect or elevated resting metabolic rate and substantial increases in maximum metabolic rate. There is also evidence that hyperoxia increases aerobic capacity improves cardiac performance and mitigates anaerobic stress during acute warming. Along with improved upper thermal tolerance in some species, these findings collectively suggest that hyperoxia might provide fish a metabolic refuge during acute warming. Since hyperoxia occurs in shallow aquatic habitats, further research establishing the ecophysiological implications of concomitant heat stress and hyperoxia is pertinent, particularly with a changing climate. [ABSTRACT FROM AUTHOR]

Aim: To determine whether closed loop automated oxygen control resulted in a reduction in the duration and severity of desaturation episodes and the number of blood gases and chest radiographs in preterm, ventilated infants. Methods: Infants were studied on two consecutive days for 12 hours on each day. They were randomised to receive standard care (standard period) or standard care with a closed loop automated oxygen control system (automated oxygen control period) first. Results: Twenty‐four infants with a median gestational age of 25.7 (range 23.1‐32.6) weeks were studied at a median postconceptional age of 27.4 (range 24.3‐34.9) weeks. During the automated oxygen control period, there were fewer desaturations that lasted >30 seconds (P =.032) or >60 seconds (P =.002), infants spent a higher proportion of the time within their target SpO2 range during the automated oxygen control period (P <.001), and fewer manual adjustments were made to the inspired oxygen concentration (mean 0.58 vs mean 11.29) (P <.001). There were no significant differences in the number of blood gases (P =.872) or chest radiographs (P =.366) between the two periods. Conclusion: Closed loop automated oxygen delivery resulted in fewer prolonged desaturations with more time spent in the targeted oxygen range. [ABSTRACT FROM AUTHOR]

The pulmonary endothelium is an immediate recipient of high oxygen concentrations upon oxygen therapy and mediates down‐stream responses. Cyclic collapse and reopening of atelectatic lung areas during mechanical ventilation with high fractions of inspired oxygen result in the propagation of oxygen oscillations in the hypoxic/hyperoxic range. We used primary murine lung endothelial cell cultures to investigate cell responses to constant and oscillating oxygen conditions in the hypoxic to hyperoxic range. Severe constant hyperoxia had pro‐inflammatory and cytotoxic effects including an increase in expression of ICAM1, E‐selectin, and RAGE at 24 hr exposure. The coagulative/fibrinolytic system responded by upregulation of uPA, tPA, and vWF and PAI1 under constant severe hyperoxia. Among antioxidant enzymes, the upregulation of SOD2, TXN1, TXNRD3, GPX1, and Gstp1 at 24 hr, but downregulation of SOD3 at 72 hr constant hyperoxia was evident. Hypoxic/hyperoxic oscillating oxygen conditions induced pro‐inflammatory cytokine release to a lesser extent and later than constant hyperoxia. Gene expression analyses showed upregulation of NFKB p65 mRNA at 72 hr. More evident was a biphasic response of NOS3 and ACE1 gene expression (downregulation until 24 hr and upregulation at 72 hr). ACE2 mRNA was upregulated until 72 hr, but shedding of the mature protein from the cell surface favored ACE1. Oscillations resulted in severe production of peroxynitrite, but apart from upregulation of Gstp1 at 24 hr responses of antioxidative proteins were less pronounced than under constant hyperoxia. Oscillating oxygen in the hypoxic/hyperoxic range has a characteristical impact on vasoactive mediators like NOS3 and on the activation of the renin‐angiotensin system in the lung endothelium. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the retinal vessel oxygen saturation in patients with internal carotid artery stenosis (ICAS). Methods: This is a cross‐sectional study. Sixteen patients with unilateral moderate or worse ICAS (≥50%) and no fundus diseases were included in the study. Sixteen gender‐ and age‐matched healthy subjects were selected as controls. The mean oxygen saturation and vessel diameters of the retinal arterioles and venules were obtained using a dual‐wavelength spectrophotometric retinal oximeter. Results: In the eye of the stenotic side, the retinal vessel oxygen saturation was 100.14 ± 10.27% in the arterioles and 56.50 ± 10.79% in the venules, and the arteriovenous (A‐V) difference was 43.63 ± 7.71%. In the eye of the contralateral side, the oxygen saturation was 96.55 ± 7.50% in the arterioles and 57.42 ± 9.84% in the venules, and the A‐V difference was 39.39 ± 6.33%. In healthy subjects, the oxygen saturation was 93.22 ± 5.98% in the arterioles and 56.57 ± 7.05% in the venules, and the A‐V difference was 36.65 ± 7.33%. The arteriolar oxygen saturation in the stenotic side was higher than that in the contralateral side (p = 0.025) and that in the healthy subjects (p = 0.027), and the A‐V difference in the stenotic side was significantly higher than that in the contralateral side (p = 0.009) and that in the healthy subjects (p = 0.013). The diameters of the arterioles in the stenotic side were smaller than those in the healthy subjects (p = 0.030). Conclusions: Patients with ICAS had decreased retinal arteriole diameters and increased retinal vessel oxygen saturation in the arterioles and A‐V differences, suggesting the presence of microcirculation disorder and hyperoxia in the retina. [ABSTRACT FROM AUTHOR]

Retinal vascularization is arrested at the early (hyperoxia) stage in retinopathy of prematurity (ROP), a leading cause of blindness in children. Estrogen was reported to alleviate ROP by inhibiting reactive oxygen species, the upstream signaling molecules of endoplasmic reticulum stress (ERS). Astrocytes have long been proposed to guide angiogenesis, because they form a reticular network that provides a substrate for migrating endothelial cells. However, the factors that control the vascularization of the immature retina and the therapeutic mechanism of estrogen in early ROP remain poorly understood. This study aimed to investigate the role of G‐protein‐coupled estrogen receptor (GPER), an estrogen receptor distributed in the endoplasmic reticulum (ER), in protecting retinal astrocytes under hyperoxia and the association with ERS. The results showed that GPER was widely expressed in retinal astrocytes. GPER activation increases cell viability, decreases apoptosis, and autophagy of retinal astrocytes, decreases inositol‐1,4,5‐triphosphate receptor activity, and increases Ca2+ concentration in ER of astrocytes under hyperoxia. GPER blockade reversed all of these changes. Together, our findings indicate that GPER can protect the survival of retinal astrocytes by inhibiting ERS under hyperoxia. [ABSTRACT FROM AUTHOR]

New Findings: What is the central question of the study?The aim was to determine the effects of duration of acceleration in the cranial–caudal direction (+Gz) on acceleration atelectasis and identify measurement techniques that can be used to assess it.What is the main finding and its importance?Non‐invasive measurement of acceleration atelectasis using electrical impedance tomography and estimates of pulmonary shunt provide more detailed assessment of acceleration atelectasis than traditional forced vital capacity measures. Using these techniques, it was found that as little as 30 s of exposure to +Gz acceleration can cause acceleration atelectasis. The results of the present study will allow a more accurate and detailed assessment of acceleration atelectasis in the future. Recently, there have been reports of acceleration atelectasis during fast jet flight despite the use of systems designed to minimize this. Before further investigation of this, indices suitable for use in applied settings and identification of acceleration durations that elicit it are required. Fifteen non‐aircrew subjects underwented five centrifuge exposures lasting 15, 30, 60 and 2 × 90 s with a plateau of +5 Gz (acceleration in the cranial‐caudal direction) while breathing 94% O2 during all but one control exposure (21% O2). Lung volumes and gas exchange limitation were assessed after each exposure. Regional lung impedance and compliance were measured after Gz exposure using electrical impedance tomography and the forced oscillatory technique, respectively. The presence of acceleration atelectasis was confirmed by reductions of 10–17% in vital and inspiratory capacity after 60 and 90 s Gz exposures (P < 0.05) and resulted in reduced regional lung impedance and a gas exchange limitation of 8.1 and 12.5%, respectively (P < 0.05). There was also a small but significant decrease in regional lung impedance after 30 s exposures. Functional residual capacity and lung compliance were unchanged in atelectatic lungs (P > 0.05). In the majority of individuals, >60 s of Gz exposure while breathing 94% O2 causes acceleration atelectasis. Electrical impedance tomography and the measurement of gas exchange limitation provide useful indicators of acceleration atelectasis. Acceleration atelectasis exerts its effects primarily through basal lung closure and reflex inspiratory limitation, both of which can be reversed by performing three maximal inspiratory breathing manoeuvres. [ABSTRACT FROM AUTHOR]

Purpose: Examine the feasibility of characterizing the regulation of renal oxygenation using high‐temporal‐resolution monitoring of the T2∗ response to a step‐like oxygenation stimulus. Methods: For T2∗ mapping, multi‐echo gradient‐echo imaging was used (temporal resolution = 9 seconds). A step‐like renal oxygenation challenge was applied involving sequential exposure to hyperoxia (100% O2), hypoxia (10% O2 + 90% N2), and hyperoxia (100% O2). In vivo experiments were performed in healthy rats (N = 10) and in rats with bilateral ischemia‐reperfusion injury (N = 4). To assess the step response of renal oxygenation, a second‐order exponential model was used (model parameters: amplitude [A], time delay [Δt], damping constant [D], and period of the oscillation [T]) for renal cortex, outer stripe of the outer medulla, inner stripe of the outer medulla, and inner medulla. Results: The second‐order exponential model permitted us to model the exponential T2∗ recovery and the superimposed T2∗ oscillation following renal oxygenation stimulus. The in vivo experiments revealed a difference in Douter medulla between healthy controls (D < 1, indicating oscillatory recovery) and ischemia‐reperfusion injury (D > 1, reflecting aperiodic recovery). The increase in Douter medulla by a factor of 3.7 (outer stripe of the outer medulla) and 10.0 (inner stripe of the outer medulla) suggests that this parameter might be rather sensitive to (patho)physiological oxygenation changes. Conclusion: This study demonstrates the feasibility of monitoring the dynamic oxygenation response of renal tissues to a step‐like oxygenation challenge using high‐temporal‐resolution T2∗ mapping. Our results suggest that the implemented system analysis approach may help to unlock questions regarding regulation of renal oxygenation, with the ultimate goal of providing imaging means for diagnostics and therapy of renal diseases. [ABSTRACT FROM AUTHOR]