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Background: Occupational noise exposure is one of the leading factors for developing noise-induced hearing loss (NIHL), particularly among workers worldwide. The literature review reveals that beside conventional strategies for preventing NIHL, multiple interventions can be applied to reduce or prevent such disorders. The present study aimed to investigate the preventive effects of normobaric hyperoxia pre- and post-treatment on the development of NIHL in rats. Methods: Four groups of male Wistar rats were exposed to pure oxygen alone, noise alone, or oxygen plus noise for 6 hours a day, 5 days a week for 4 weeks. One group served as the control and received neither noise nor oxygen. Animals in the noise groups were exposed to high-pass white noise of 100 dB SPL, centred at 8 KHz. The treatment protocols were based on inhalation of pure normobaric oxygen (95%) for 3 hours in a chamber either before or after noise exposure. The auditory brainstem responses (ABRs) for click and 4, 6, 8, 12, and 16 kHz stimuli, as well as distortion product otoacoustic emissions (DPOAEs) at 4, 6, 8, and 10 kHz, were recorded to assess the level of hearing impairment before exposure and 4 weeks post-exposure. Results: The results showed that pre-treatment of rats with 3 hours of normobaric hyperoxia contributed to a significant reduction in ABR threshold shifts, while improving the DPOAE amplitudes (P 0.05). Conclusions: Pre- and post-treatment with normobaric hyperoxia seem to produce protective effects through either boosting cellular oxygenation or maximizing antioxidant enzyme activities and tolerance against noise-induced ischemia and hypoxia in the cochlea. Therefore, application of normobaric hyperoxia pre- or post-treatment, along with other conventional protective strategies, can be helpful in the fight against NIHL.

Hypoxic ischemic brain injury (HIBI) after cardiac arrest (CA) is a leading cause of mortality and long-term neurologic disability in survivors. The pathophysiology of HIBI encompasses a heterogeneous cascade that culminates in secondary brain injury and neuronal cell death. This begins with primary injury to the brain caused by the immediate cessation of cerebral blood flow following CA. Thereafter, the secondary injury of HIBI takes place in the hours and days following the initial CA and reperfusion. Among factors that may be implicated in this secondary injury include reperfusion injury, microcirculatory dysfunction, impaired cerebral autoregulation, hypoxemia, hyperoxia, hyperthermia, fluctuations in arterial carbon dioxide, and concomitant anemia. Clarifying the underlying pathophysiology of HIBI is imperative and has been the focus of considerable research to identify therapeutic targets. Most notably, targeted temperature management has been studied rigorously in preventing secondary injury after HIBI and is associated with improved outcome compared with hyperthermia. Recent advances point to important roles of anemia, carbon dioxide perturbations, hypoxemia, hyperoxia, and cerebral edema as contributing to secondary injury after HIBI and adverse outcomes. Furthermore, breakthroughs in the individualization of perfusion targets for patients with HIBI using cerebral autoregulation monitoring represent an attractive area of future work with therapeutic implications. We provide an in-depth review of the pathophysiology of HIBI to critically evaluate current approaches for the early treatment of HIBI secondary to CA. Potential therapeutic targets and future research directions are summarized.

Prospective, randomized and controlled study.The aim of the study was to investigate the effect of intermittent normobaric hyperoxia (InHO) for treatment of neuropathic pain in patients with spinal cord injury (SCI).The First Affiliated Hospital of Nanhua University, Hengyang, Hunan Province, China.Patients with SCI from Hunan Province were recruited from the First Affiliated Hospital of Nanhua University. History, duration, localization and characteristics of pain were recorded. Visual analog scale (VAS), the Patient Global Impression of Change (PGIC) and Short Form-36 walk-wheel (SF-36ww) was used to investigate the effect of InHO. Patients were randomly assigned to study and control groups. In study group, patients were exposed to pure oxygen via non-rebreathing reservoir mask, which increased the provided oxygen at a rate of 7 l minA total of 62 SCI patients with neuropathic pain were included in the study. The mean age of the patients was 36.85±10.71 years. Out of 62 patients, 21 were tetraplegic and 41 were paraplegic. Overall, 14 patients had complete SCI while 48 patients had incomplete injuries. Three groups were similar with respect to age, gender, duration, smoker or not, level and severity of injury. In the 4 h per day InHO groups, a statistically significant reduction of the VAS values was observed (P0.05). Significant difference was also found in SF-36ww pain scores and PGIC (P0.05). However, such an effect was not evident in the control group.This study revealed that in treatment of neuropathic pain of SCI patients, InHO may be effective.This article presents InHO may effectively complement pharmacological treatment in patients with SCI and neuropathic pain.

Dopamine (DA) is one of the key neurotransmitters in the striatum, which is functionally important for a variety of cognitive and motor behaviours. It is known that the striatum is vulnerable to damage from traumatic brain injury (TBI). However, a therapeutic approach has not yet been established to treat TBI. Hence, the present work aimed to evaluate the ability of Normobaric hyperoxia treatment (NBOT) to recover dopaminergic neurons following a fluid percussion injury (FPI) as a TBI experimental animal model. To examine this, mice were divided into four groups: (i) Control, (ii) Sham, (iii) FPI and (iv) FPI+NBOT. Mice were anesthetized and surgically prepared for FPI in the striatum and immediate exposure to NBOT at various time points (3, 6, 12 and 24 h). Dopamine levels were then estimated post injury by utilizing a commercially available ELISA method specific to DA. We found that DA levels were significantly reduced at 3 h, but there was no reduction at 6, 12 and 24 h in FPI groups when compared to the control and sham groups. Subjects receiving NBOT showed consistent increased DA levels at each time point when compared with Sham and FPI groups. These results suggest that FPI may alter DA levels at the early post-TBI stages but not in later stages. While DA levels increased in 6, 12 and 24 h in the FPI groups, NBOT could be used to accelerate the prevention of early dopaminergic neuronal damage following FPI injury and improve DA levels consistently.

Reported recovery effects of hyeroxia are conflicted. This study aimed to identify the effects and the mechanisms of normobaric hyperoxia on the recovery of local muscle fatigue, which is the most commonly encountered form of fatigue both daily and in training and competitions. Twelve male subjects performed 3 × 3 × no less than 30 seconds of isometric quadriceps exercise at 70% of maximum voluntary isometric contraction (MVIC) separated by two 15-minute recovery sessions under 1 of 2 different atmospheric oxygen concentrations, one in normoxia (NOX; 20.9% O2) and another in hyperoxia (HOX; 30.0% O2). To assess the degree of fatigue and recovery, 4 parameters were used; MVIC, endurance time to exhaustion, blood lactate, and perceived exertion measured by a visual analog scale (VAS). Maximum voluntary isometric contraction improved an average by approximately 14% in HOX compared with NOX at the conclusion of the second recovery session. However, this was not associated with changes in other parameters because changes in endurance time, blood lactate, and VAS during the trials were similar. Based on our findings, we conclude that 2 sets of 15-minute recovery session in normobaric hyperoxia are effective for restoring MVIC from local muscle fatigue induced by intermittent intense exercises. For quicker recovery, athletes are recommended to repeat 15-minute recovery process under 30.0% hyperoxia.

Background Recent studies suggest that normobaric hyperoxia (HO) reduces hypoxia-reoxygenation injury in the rat brain. We have attempted to determine the effect of HO on Na + –Ca 2+ exchangers (NCX) in the rat stroke model. Methods Rats were divided into two experimental groups. The first group was exposed to 95% inspired HO for 4 h/day for 6 consecutive days (HO). The second group acted as the control, and was exposed to 21% oxygen in the same chamber. Each main group was subdivided to middle cerebral artery occlusion (MCAO-operated) and intact (without any surgery) subgroups. After 48 h from pretreatment, MCAO-operated subgroups were subjected to 60 min of right MCAO. After 24 h reperfusion, neurologic deficit score (NDS) and infarct volume were measured in MCAO-operated subgroups. The NCXs expression levels of the core, penumbra and subcortical regions were assessed in sham-operated and intact subgroups. Result Preconditioning with HO decreased NDS and infarct volume, and increased the expression of NCX1, NCX2 and NCX3 in the penumbra, NCX2, NCX3 in the core and NCX1 and NCX3 in the subcortex. Conclusion Although further studies are needed to clarify the mechanisms of ischemic tolerance, HO partly is associated with the expression of NCX1, 2, 3 consistent with an active role in the genesis of ischemic protection.

Introduction Ischemic stroke is a global burden that contributes to the disability and mortality of millions of patients. This study aimed to evaluate the efficacy of combined MB (methylene blue) and NBO (normobaric hyperoxia) therapy in experimental ischemic stroke. Methods Rats with transient (60 min) MCAO (middle cerebral artery occlusion) were treated with: (1) air + vehicle (N = 8), (2) air + MB (N = 8), (3) NBO + vehicle (N = 7), and (4) NBO + MB (N = 9). MB (1 mg/kg) was administered at 30 min, again on days 2, 7, and 14 after stroke. NBO was given during MRI (30–150 min) on day 0, and again 1 h each during MRI on subsequent days. Serial diffusion, perfusion and T2 MRI were performed to evaluate lesion volumes. Foot-fault and cylinder tests were performed to evaluate sensorimotor function. Results The major findings were: (1) NBO + MB therapy showed a greater decrease in infarct volume compared to NBO alone, but similar infarct volume compared to MB alone, (2) NBO + MB therapy accelerated sensorimotor functional recovery compared to NBO or MB alone, (3) Infarct volumes on day 2 did not change significantly from those on day 28 for all four groups, but behavioral function continued to show improved recovery in the NBO + MB group. Conclusions These findings support the hypothesis that combined NBO + MB further improves functional outcome and reduces infarct volume compared to either treatment alone and these improvements extended up to 28 days.

Several studies of normobaric hyperoxia in neurological conditions have found positive results. The impaired energy metabolism due to mitochondrial dysfunction and frontal lobe hypofunction in schizophrenia might be improved by increasing O2 supply to the brain. Normobaric hyperoxia may be a potential treatment for schizophrenia. Participants in this study, outpatients with chronic schizophrenia and inhabitants of community-based psychiatric institutions (hostels), underwent baseline psychiatric/cognitive assessment and were randomly assigned to either a treatment intervention of oxygen-enriched air inhalation (normobaric hyperoxia of 40% fraction of inspired oxygen) or regular air inhalation (21% fraction of inspired oxygen), through a nasal tube, for 4 weeks. Patients were given the air/oxygen inhalations during the night (mainly while sleeping) for at least 7 hours a night. After completing 4 weeks of treatment, patients were switched (crossed over) to the other treatment intervention. Fifteen patients completed the entire study. Five additional patients completed phase A only. There was significant improvement in total Positive and Negative Symptoms Scale score of patients who received oxygen compared with the control group. There were positive effects of oxygen on memory and attention in neuropsychological performance tests. The effect size is small despite the statistical significance, but the patient group was extremely chronic and severely impaired. These results are a proof of concept, and normobaric hyperoxia should be studied in patients with milder forms of the illness and earlier in the course of illness.

Eur J Clin Invest 2012; 42 (3): 260–265 Abstract Background Based on a report of a marked increase in the erythropoietin concentration ([EPO]) a few hours after the cessation of a single 2-h session of O2 breathing, short periods of O2 administration have been advocated as a therapy for anaemia. Accordingly, the purpose of the present study was to evaluate this theory by investigating the effect of 10 daily short-term exposures to normobaric O2 over a 2-week period on the plasma [EPO] in healthy individuals. Material and methods Twenty men were assigned to either an experimental (NBO2) or to a control (AIR) group. The NBO2 group breathed 100% normobaric O2 for 2 h every weekday over a 2-week period. The AIR group breathed air within the same time protocol. Blood samples were collected at the pre-, mid- and post-intervention periods to determine [EPO]. Results [EPO] of the NBO2 group was significantly lower than that of the AIR group during the mid- and post-periods (P

Aim: The purpose of the present study was to evaluate the ‘normobaric oxygen paradox’ theory by investigating the effect of a 2-h normobaric O2 exposure on the concentration of plasma erythropoietin (EPO). Methods: Ten healthy males were studied twice in a single-blinded counterbalanced crossover study protocol. On one occasion they breathed air (NOR) and on the other 100% normobaric O2 (HYPER). Blood samples were collected Pre, Mid and Post exposure; and thereafter, 3, 5, 8, 24, 32, 48, 72 and 96 h, and 1 and 2 weeks after the exposure to determine EPO concentration. Results: The concentration of plasma erythropoietin increased markedly 8 and 32 h after the NOR exposure (approx. 58% and approx. 52%, respectively, P £ 0.05) as a consequence of its natural diurnal variation. Conversely, the O2 breathing was followed by approx. 36% decrement of EPO 3 h after the exposure (P £ 0.05). Moreover, EPO concentration was significantly lower in HYPER than in the NOR condition 3, 5 and 8 h after the breathing intervention (P £ 0.05). Conclusion: In contrast to the ‘normobaric oxygen paradox’ theory, the present results indicate that a short period of normobaric O2 breathing does not increase the EPO concentration in aerobically fit healthy males. Increased O2 tension suppresses the EPO concentration 3 and 5 h after the exposure; thereafter EPO seems to change in a manner consistent with natural diurnal

Pretreatment with HBO at 300-500 kPa for 20 min reduced the incidence of decompression sickness (DCS) in a rat model. We investigated whether this procedure would be effective with lower oxygen pressures and shorter exposure, and tried to determine how long the pretreatment would remain effective. Rats were pretreated with oxygen at 101 or 203 kPa for 20 min and 304 kPa for 5 or 10 min. After pretreatment, the animals were exposed to air at 1,013 kPa for 33 min followed by fast decompression. Pretreatment at 101 or 203 kPa for 20 min and 304 kPa for 10 min significantly reduced the number of rats with DCS to 45%, compared with 65% in the control group. However, after pretreatment at 304 kPa for 5 min, 65% of rats suffered DCS. When pretreatment at 304 kPa for 20 min was followed by 2 h in normobaric air before compression and decompression, the outcome was worse, with 70-90% of the animals suffering DCS. This is probably due to the activation of "dormant" micronuclei. The risk of DCS remained lower (43%) when pretreatment with 100% O(2) at normobaric pressure for 20 min was followed by a 2 h interval in normobaric air (but not 6 or 24 h) before the hyperbaric exposure. The loss of effectiveness after a 6 or 24 h interval in normobaric air is related to micronuclei rejuvenation. Although pretreatment with hyperbaric O(2) may have an advantage over normobaric hyperoxia, decompression should not intervene between pretreatment and the dive.

Background: Low brain tissue oxygen tension (PbtO2), or brain hypoxia, is an independent predictor of poor outcome. Increasing inspirational fraction of oxygen could have a significant influence on treating lower PbtO2. Combined PbtO2 therapy, compared to the approach that focus only on regulation of cerebral perfusion pressure and intracranial pressure, shows better patient outcomes. Monitoring of PbtO2 could be helpful in individualizing treatment, preventing or limiting secondary brain injury, and maintaining better patient outcome. Case Description: We present a case of a patient with subarachnoidal hemorrhage to whom PbtO2 monitor was implanted, and normobaric hyperoxia treatment was adjusted according to PbtO2 measurement. The patient progressively recovered and was dismissed with Glasgow Coma Score 4/5/6. Conclusion: The use of PbtO2 monitoring may be useful for monitoring the local tissue values that are useful for induction of normobaric hyperoxia and optimizing the therapy toward more target-defined values. It is an important part of multimodal neuromonitoring, and is the gold standard for brain oxygenation monitoring that can lead to better patient outcome.

Traumatic brain injury (TBI) and acute ischaemic stroke are major causes of mortality and morbidity and there is an urgent demand for new neuroprotective strategies following the translational failure of neuroprotective drug trials. Oxygen therapy--especially normobaric, may offer a simple and effective therapeutic strategy which we review in this paper. Firstly we review mechanisms underlying the therapeutic effects of hyperoxia (both normobaric and hyperbaric) including mitochondrial rescue, stabilisation of intracranial pressure, attenuation of cortical spreading depression and inducing favourable endothelial-leukocyte interactions, all effects of which are postulated to decrease secondary injury. Next we survey studies using hyperbaric oxygen therapy for TBI and stroke, which formed the basis for early studies on normobaric hyperoxia. Thirdly, we present clinical studies of the efficacy of normobaric hyperoxia on TBI and stroke, emphasising their safety, efficacy and practicality. Finally we consider safety concerns and side effects, particularly pulmonary pathology, respiratory failure and theoretical risks in paediatric patients. A neuroprotective role of normobaric hyperoxia is extremely promising and further studies are warranted.

Introduction: Ischemic preconditioning (IPC) is an endogenous phenomenon that can induce ischemic tolerance (IT) in variety of organs such as brain. In this study, we examined the intermittent and prolonged dose of normobaric hyperoxia (HO) on neurologic deficit scores, infarct volume, and catalase activity. Material and Method: The rats were divided to four main groups. First two main groups were exposed with HO in prolonged (24h PrHO) and intermittent (4h×6days InHO) groups and second two main group acted as controls, and were exposed to 21% oxygen in the same chamber (room air, RA) continuously (24h PrRA) and discontinuously (4h×6days InRA). Each group subdivided to three subgroups. After 24 h, first subgroup were subjected to 60 minutes MCAO followed by 24h of reperfusion. Then, IT induced by InHO and PrHO were measured by neurologic deficit scores and infarct volume. Second and third subgroups were called sham-operated and intact subgroups for assessment of the effect of HO on catalase activity. Result: Our findings indicate that InHO and PrHO are involved in the induction of IT. Pretreatment with InHO and PrHO reduced neurologic deficit scores and infarct volume significantly. InHO and PrHO increase catalase activity significantly. The catalase activity of prolonged HO groups significantly was more than that of intermittent HO groups. Conclusion: Although further studies are needed to clarify the mechanisms of ischemic tolerance, InHO and PrHO seem to partly exert their effects via increase catalase activity.

We evaluated the potential neuroprotective effects of combination treatment with normobaric hyperoxia (NBO) and edaravone, a potent scavenger of hydroxyl radicals, on acute brain injuries after stroke. Mice subjected to 2-h filamental middle cerebral artery occlusion were treated with NBO (95% O2, during the ischemia) alone, with edaravone (1.5 mg/kg, intravenously after the ischemia) alone, with both of these treatments (combination), or with vehicle. The histological and neurological score were assessed at 22-h after reperfusion. Infarct volume was significantly reduced in the combination group [36.3+/-6.7 mm3 (n=10) vs. vehicle: 65.5+/-5.9 mm3 (n=14) P0.05], but not in the two monotherapy-groups [NBO: 50.5+/-5.8 mm3 (n=14) and edaravone: 56.7+/-5.8 mm3 (n=10)]. The combination therapy reduced TUNEL-positive cells in the ischemic boundary zone both in cortex [6.0+/-1.4 x 10(2)/mm2 (n=5) vs. vehicle: 18.9+/-2.4 x 10(2)/mm2 (n=5), P0.01] and subcortex [11.6+/-1.5 x 10(2)/mm2 (n=5) vs. vehicle: 22.5+/-2.1 x 10(2)/mm2 (n=5), P0.01]. NBO and combination groups exhibited significantly reduced neurological deficit scores at 22-h after reperfusion (vs. vehicle, P0.05). Combination therapy with NBO plus edaravone prevented the neuronal damage after focal cerebral ischemia and reperfusion in mice, compared with monotherapy of NBO or edaravone.

To determine the effect of normobaric hyperoxia on cerebral metabolism in patients with severe traumatic brain injury.Prospective clinical investigation.Neurosciences critical care unit of a university hospital.Eleven patients with severe traumatic brain injury.Cerebral microdialysis, brain tissue oximetry (PbO2), and oxygen-15 positron emission tomography (15O-PET) were undertaken at normoxia and repeated at hyperoxia (FiO2 increase of between 0.35 and 0.50).Established models were used to image cerebral blood flow, blood volume, oxygen metabolism, and oxygen extraction fraction. Physiology was characterized in a focal region of interest (surrounding the microdialysis catheter) and correlated with microdialysis and oximetry. Physiology was also characterized in a global region of interest (including the whole brain), and a physiologic region of interest (defined using a critical cerebral metabolic rate of oxygen threshold). Hyperoxia increased mean +/- sd PbO2 from 28 +/- 21 mm Hg to 57 +/- 47 mm Hg (p = .015). Microdialysate lactate and pyruvate were unchanged, but the lactate/pyruvate ratio showed a statistically significant reduction across the study population (34.1 +/- 9.5 vs. 32.5 +/- 9.0, p = .018). However, the magnitude of reduction was small, and its clinical significance doubtful. The focal region of interest and global 15O-PET variables were unchanged. "At-risk" tissue defined by the physiologic region of interest, however, showed a universal increase in cerebral metabolic rate of oxygen from a median (interquartile range) of 23 (22-25) micromol x 100 mL(-1) x min(-1) to 30 (28-36) micromol x 100 mL(-1) x min(-1) (p.01).In severe traumatic brain injury, hyperoxia increases PbO2 with a variable effect on lactate and lactate/pyruvate ratio. Microdialysis does not, however, predict the universal increases in cerebral metabolic rate of oxygen in at-risk tissue, which imply preferential metabolic benefit with hyperoxia.

This study focuses on the effect of hyperoxia on maximal oxygen uptake \( {\left( {\ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{{2\max }} } \right)} \) and maximal power (Pmax) in subjects exhibiting exercise-induced arterial hypoxemia (EIH) at sea level. Sixteen competing male cyclists \( \ifmmode\expandafter\dot\else\expandafter\.\fi{V}{\text{O}}_{{2\max }} \)>60 ml·min−1·kg−1) performed exhaustive ramp exercise (cycle-ergometer) under normoxia and moderate hyperoxia (FIO2=30%). After the normoxic trial, the subjects were divided into those demonstrating EIH during exercise [arterial O2 desaturation (Δ SaO2) >5%; n=9] and those who did not (n=7). Under hyperoxia, SaO2 raised and the increase was greater for the EIH than for the non-EIH group (P

Objective: Surgery for posterior fossa lesions is often performed in a semisitting position which provides distinct advantages but which may be burdened also by serious side effects. In particular, supratentorial pneumocephalus which may lead to decreased alertness and other symptoms is a common problem.[for full text, please go to the a.m. URL], 65. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

The purpose of this study was to determine if normobaric hyperoxia (HO) pre-conditioning offers durable neuroprotection against cerebral ischaemia and its effects on NCX1 expression.Rats were divided into two experimental groups. The first group was exposed to 95% inspired HO for 4 hours/day for 6 consecutive days (HO). The second group acted as control and was exposed to 21% oxygen in the same chamber. Each main group was sub-divided to middle cerebral artery occlusion (MCAO-operated) and intact (without any surgery) sub-groups. After 2, 5, 10 and 15 days from pre-treatment, MCAO-operated sub-groups were subjected to 60 minutes of right MCAO. After 24 hours reperfusion, neurologic deficit score and infarct volume were measured in MCAO-operated sub-groups. The NCX1 expression levels of core, penumbra and sub-cortex regions were assessed in sham-operated and intact sub-groups.Pre-conditioning with HO decreased neurologic deficit score and infarct volume, and increased expression of NCX1 in penumbra and sub-cortex. These effects of hyperoxia disappeared gradually during 15 days after pre-treatment.Although further studies are needed to clarify the mechanisms of time course of neuroprotection, HO partly is associated with expression of NCX1 consistent with an active role in the genesis of ischaemic neuroprotection.

Ischemia and metabolic dysfunction remain important causes of neuronal loss after head injury, and we have shown that normobaric hyperoxia may rescue such metabolic compromise. This study examines the impact of hyperoxia within injured brain using diffusion tensor imaging (DTI). Fourteen patients underwent DTI at baseline and after 1 hour of 80% oxygen. Using the apparent diffusion coefficient (ADC) we assessed the impact of hyperoxia within contusions and a 1 cm border zone of normal appearing pericontusion, and within a rim of perilesional reduced ADC consistent with cytotoxic edema and metabolic compromise. Seven healthy volunteers underwent imaging at 21%, 60%, and 100% oxygen. In volunteers there was no ADC change with hyperoxia, and contusion and pericontusion ADC values were higher than volunteers (P

Background: Exposure to partial pressures of oxygen (PO2) higher than 50 kPa may result in toxic effects on the lungs with reduced vital capacity, maximal expiratory flow rates and diffusion capacity. The risk of developing pulmonary oxygen toxicity is present during diving and hyperbaric oxygen therapy. The traditional lung function tests are not sufficiently sensitive, and new markers of early development of oxygen toxicity are required. Nitric oxide (NO) in exhaled gas is a marker of some inflammatory processes in the lungs and the production of NO is influenced by the PO2. The fraction of NO in exhaled gas (FENO) is reduced by 30% after exposure to hypobaric hypoxia at altitude above 4500meter. NO from the alveolar and bronchial compartments of the lung contribute to FENO. Changes in NO concentration at the alveolar level may have effects on pulmonary blood flow and gas exchange, and thereby contribute to the reduction in diffusion capacity. A reduction in bronchial NO flux is associated with induced bronchoconstriction, while increased alveolar NO concentration is associated with increased alveolar dead space. Aims: The overall aim in the present thesis was to investigate if FENO is a useful marker to predict pulmonary oxygen toxicity. This was investigated through three separated studies that aimed at: 1. To study the dose-response relationship between oxygen exposure and FENO during and after hypoxia and hyperoxia. 2. To investigate the alveolar and bronchial contributions in FENO after exposure to hyperoxia. 3. To investigate the relationship between FENO and lung function. Design: An open randomised crossover design and a non-randomized design. Methods: 73 healthy non-smoking subjects between the ages of 20-40 years and a smaller group of 12 patients between 35-68 years undergoing hyperbaric oxygen therapy were included. FENO was measured before, during and after exposure to hypobaric hypoxia (PO2 = 15 kPa), hyperbaric hyperoxia (PO2 = 240 kPa), normobaric hyperoxia (PO2 = 100 kPa) and when breathing ambient air (PO2 = 21 kPa), all for 90 min. Dynamic and static lung volumes, maximal expiratory flow rates, distribution of ventilation and diffusion capacity (DLCO) were measured before and after exposure to normobaric hyperoxia. Results: The concentration of NO in exhaled gas was reduced by 20-30% after exposure to hyperoxia at PO2 of 100-240 kPa, but no significant change was found after exposure to hypoxia when corrected for altitude effects. The bronchial contribution to NO in exhaled gas was reduced after exposure to hyperoxia, whereas the alveolar NO concentration was unchanged. There was no association between the change in FENO and the changes in lung function after exposure to normobaric hyperoxia. Conclusions: 1. The partial pressure of NO in exhaled gas was unchanged upon arrival at moderate altitude after correcting for gas density effects. There might be a dose-response relationship between PO2 and the change in FENO, where subjects exposed to the highest dose of oxygen showed the greatest reduction in FENO. 2. There was a significant reduction in bronchial contribution to NO in exhaled gas after hyperoxia, but no change in the alveolar NO concentration. 3. The reduction in FENO by 20% after exposure to hyperoxia at PO2 of 100 kPa for 90 min was not associated with the changes in lung function. FENO was not confirmed as a direct marker of pulmonary oxygen toxicity.

[Purpose] Acute development of local muscle fatigue and recovery often become large issues on sports fields. This study aimed to identify the effects of normobaric hyperoxia on the recovery of local muscle fatigue. [Subjects] Eleven healthy males participated in this study, and they all completed two protocols in a random order. [Methods] Subjects performed single-leg isometric knee extension at 70% of their maximum voluntary isometric contraction (MVIC) for as long as possible. Each participant was subsequently treated with one of two recovery conditions: 20.9% O2 or 30.0% O2 for 30 minutes. Afterwards, they performed an identical isometric task to measure the extent of their recovery. The following parameters were used to assess the degrees of muscle fatigue: MVIC, endurance time, surface electromyography (sEMG) power spectra, and changes in hemoglobin concentration using near-infrared spectroscopy (NIRS). [Results] The treatment of 30.0% O2 induced a significant recovery rate in MVIC compared to the 20.9% O2. Additionally, the data revealed a significantly higher concentration of total hemoglobin after the 30.0% O2 treatment than after the 20.9% O2 treatment. [Conclusion] The results of this study suggest that recovery from acute muscle fatigue can be better facilitated under 30.0% normobaric hyperoxia than a normoxic condition. Therefore, for cases requiring quicker full recovery, treatment under 30.0% O2 environment for 30 minutes is recommended.

Sir, We thank Chazalviel et al. (2016) for their interest in our article (Ejaz et al. , 2016) showing near-complete protection against neuronal damage and sensorimotor deficit by normobaric hyperoxia (NBO) in a rat model of brief middle cerebral artery occlusion (MCAO). Chazalviel et al. raise interesting issues regarding potential interactions between NBO and tissue plasminogen activator (tPA). To summarize, they argue that the available data from thrombo-embolic stroke models suggest that NBO when administered before tPA facilitates the latter’s thrombolytic properties, in turn increasing the chance of reperfusion and improved cerebral blood flow (CBF). Chazalviel et al. go one step further by arguing that the beneficial effects of NBO in experimental stroke may be largely, if not solely, due to this effect on perfusion, rather than to the—admittedly modest—increase in arterial oxygen content. Although their point that NBO facilitates the thrombolytic effects of tPA is important and may account for the previously reported synergism of NBO and tPA in reducing infarct volume (Henninger et al. , 2009), we believe it unlikely this to be the sole mechanism underlying the beneficial effects of NBO, and believe the latter are at least in part due to improved arterial oxygen. Several lines of evidence support this view, as follows

Recent studies suggest that normobaric hyperoxia (HO) protects the rat brain from ischemia reperfusion (IR) injury. Protein kinase C (PKC) is a key signaling molecule involved in protection against IR injury but its role in protective effect of HO in brain injury in unknown. In this study we attempted to see if PKC is involved in the effect of HO. Rats were divided into four main experimental groups. The first two were exposed to 95 % oxygen (HO) in a chamber 4 h/day for 6 consecutive days. Each of these groups had a control group exposed to 21 % oxygen. To investigate the role of PKC during HO, chelerythrin chloride (CHEL, 1 mg/kg/day), a PKC inhibitor, or its vehicle was given to animals for 6 days. After 24 h, the rats were subjected to 60 min of right middle cerebral artery occlusion (MCAO). After 24 h reperfusion neurological deficit scores, infarct volume, brain edema and blood–brain Barrier (BBB) permeability were assessed. HO decreased the infarct volume and brain edema in comparison with controls. PKC inhibition was associated with a significant increase in infarct size in both HO and control animals. PKC inhibition was unable to change brain edema in the experimental groups. Both HO and PKC inhibition reduced the BBB permeability within 24 h post occlusion of middle cerebral artery. Although both HO and PKC inhibition were associated with inhibition of BBB permeability during ischemic brain injury in rats, the neuroprotective effect of HO was independent of PKC in the MCAO model., EXCLI Journal ; Vol. 11, 2012

The purpose of this study was to determine if normobaric hyperoxia (HO) preconditioning offers durable neuroprotection against cerebral ischemia and the role of reactive oxygen species in the ischemic tolerance mechanism.Rats were divided into four experimental main groups. First main group which was comprised four subgroups, were exposed to 90% HO for 6 days, 4 hours per day and subjected to 60 minutes of right middle cerebral artery occlusion (MCAO) after 2, 5, 10, and 15 days. Second group acted as control, was exposed to 21% oxygen (RA; room air) in the same chamber, and subjected to 60 minutes of right MCAO. Third main group comprised two subgroups, were exposed to 90% HO for 6 days, 4 hours per day, received normal saline (NS; 2HO+NS) and dimethylthiourea (DT) just before inhaling 90% HO (2HO+DT). Forth main group was exposed to 21% oxygen (2RA) in the same chamber and received normal saline (2RA+NS) and DT just before inhaling 21% oxygen (2RA+DT). Last two main groups were subjected to 60 minutes of right MCAO after 2 days. After 24-hour reperfusion, neurological deficit score (NDS), infarct volume, brain water content, and Evans blue extravasations were assessed in all animals.First main group compared with the RA group, NDS, infarct volume, Brain water content, and Evans blue extravasations were reduced in 2, 5, and 10 days significantly, whereas there was no difference among groups 2HO+DT, 2RA+DT, and 2RA+NS.In the model of transient focal cerebral ischemia, hyperoxia preconditioning induced effective but transient neuroprotective effects.

To the Editor: We read with interest the article by Liu et al, published in the July issue of Stroke. 1 The authors demonstrate that early normobaric hyperoxia (NBO) treatment increases the safety of delayed tPA thrombolysis in a rat model of focal cerebral ischemia and can extend its therapeutic time window. They …

Background In our previous study, it was indicated that pre-exposing rats to normobaric hyperoxia could induce a late preconditioning against infarction and arrhythmia. In this study, attempts were made to know whether the intermittent pre-exposure to the same environment could prolong the late phase of hyperoxia preconditioning. Methods In the first series of experiments, rats were divided into five groups; group 1 was pre-exposed to normal air (NOR) and the other groups to hyperoxic air (O 2 > 95%, 120 min once a d) 12, 24, 48, and 72 h (H12, H24, H48, and H72 groups) before 30 min ischemia. In the second series of experiments, rats were pre-exposed to intermittent hyperoxic air (1, 2, or 3 consecutive d) at different times before being subjected to ischemia (H48, H2-48, H2-72, H3-72, and H3-96 groups). The infarct size was measured by triphenyltetrazolium chloride staining, and lead II of electrocardiogram recorded to monitor ischemic-induced arrhythmia. Results Compared with NOR group, the infarct size and incidence of arrhythmia were reduced significantly in H24 and H48 groups. When the exposure periods were enhanced to 2 d, the infarct size did not decrease significantly, but the incidence of arrhythmia reduced. When the pre-exposure times were enhanced to 3 d, both the infarct size and incidence of arrhythmia decreased significantly in H3-72 group, but not in H3-96 group. Conclusion These results show that the late phase of hyperoxia preconditioning may last for more than 48 h and prolong by intermittent per-exposure to the same environment.

It is well known that oxygen acts as a vasoconstrictor. We evaluated the impact of normobaric hyperoxia on the sublingual microcirculation in critically ill patients.

A major limitation in thrombolysis for acute ischemic stroke is the restricted time window for safe and effective therapy. Any method that can extend the reperfusion time window would be important. In this study, we show that normobaric hyperoxia extends the time window for effective reperfusion from 1 to 3 hours in rats subjected to focal cerebral ischemia. Normobaric hyperoxia did not increase cellular markers of superoxide generation or brain levels of matrix metalloproteinase-9. Normobaric hyperoxia may be a clinically feasible adjunct method for significantly increasing the time window for effective thrombolytic therapy in acute ischemic stroke.

Fifteen healthy volunteers were exposed to a stepwise increase in FIO2 between 0.21 and 1.0, and their haemodynamic responses were measured with a non-invasive transthoracic bio-impedance monitor. There was mean reduction in cardiac index from 3.44 to 3.08 l.min-1.m-2 (10.7%, p < 0.001). The mean reduction in heart rate was from 77.3 to 69.1 beats.min-1 (10.5%, p < 0.001) and the mean systemic vascular index increased from 2062 to 2221 dyne.s-1.cm-5.m-2 (7.7%, p < 0.025). There were no significant changes in stroke index or mean arterial pressure. These changes are similar quantitatively and qualitatively to those previously reported by dye dilution techniques.

The cell ultrastructure and some detoxifying enzyme activities were studied in skeletal muscles of young rats kept for 84 h under normobaric hyperoxia (95% O2) or normoxia as control. Rat were injected ip. Every 12 h either with lml saline, 1 ml saline +30 mg hypotaurine or 1 ml saline +30 mg taurine. Ultrastructural observation revealed an highly protective effect on tissue damages due to hyperoxia in taurinetreated rats and, at less extent, in hypotaurine-treated ones. Enzymatic assays suggest a different mechanism of the two molecules in their protective action.

Background Normobaric hyperoxia (NBO) therapy is neuroprotective in acute ischemic stroke. However, how long the NBO should last to obtain optimal outcome is still unclear. Reports show that ischemic penumbra blood supply may remain compromised for a long period after ischemia-reperfusion, which would impair tissue oxygenation in ischemic penumbra. Therefore, we hypothesized that longer-lasting NBO may yield greater neuroprotection. Methods The relationship between treatment outcome and NBO duration was examined in this study. Rats were subjected to 90 min middle cerebral artery occlusion followed by reperfusion for 22.5 hours. NBO started at 30 min post ischemia and lasted for 2, 4 or 8 h. Treatment efficacy was evaluated by measuring infarction volume, oxidative stress and apoptosis. Results Among 2 h, 4 h and 8 h NBO, 8 h NBO offered the greatest efficacy in reducing 24-hour infarction volume, attenuating oxidative stress that was indicated by decreased production of 8-hydroxydeoxyguanosine and NADPH oxidase catalytic subunit gp91phox, and alleviating apoptosis that was associated with reduced production of DNA fragment and caspase-3 activity in cortex penumbra. Conclusions Under our experimental conditions, longer duration of NBO treatment produced greater benefits in focal transient cerebral ischemia-reperfusion rats.

To test whether heavy accumulation of ceroid/lipofuscin can disturb important functions of the lysosomal system, AG-1518 human fibroblasts, ceroid/lipofuscin-loaded (following prolonged culture at normobaric hyperoxia) or not, were exposed to amino acid starvation. Ceroid/lipofuscin-loading resulted in decreased cellular survival. Also, there was an inverse relationship between amounts of ceroid/lipofuscin and the survival time of individual cells within the same cultures. Ceroid/lipofuscin-loaded fibroblasts displayed diminished autophagocytotic capacity, as demonstrated by electron microscopy and by treatment of cell cultures with NH4Cl (which inhibits autophagocytotic degradation by increasing intralysosomal pH) for 1 week before ensuing starvation. The latter treatment increased survival of control cells (due to deposition of nondegraded autophagocytosed material before start of starvation), but not that of ceroid/lipofuscin-loaded cells. Moreover, when NH4Cl treatment was combined with starvation, both groups of cells showed approximately the same shortened survival times, testifying to the causal relationship between diminished autophagocytosis and decreased survival of starving ceroid/lipofuscin-loaded cells. We hypothesize that large amounts of undegradable ceroid/lipofuscin within the acidic vacuolar compartment may interfere with lysosomal function, resulting in poor renewal of long-lived proteins and worn-out/damaged organelles, decreased adaptability, and cell death.

The effect of normobaric hyperoxia on voluntary salt intake was investigated in 20 sham-operated and 11 carotid body-denervated SHR. While in sham-operated SHR the saline intake was enhanced during the whole hyperoxic period, the carotid body-denervated rats showed an increase in salt appetite only on the second and third day of hyperoxia. Water intake was not significantly different in sham-operated and carotid body-denervated SHR. These findings, together with our previous results, suggest that chemoreceptor activity determines salt appetite but not water intake in SHR.