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Representative experiment showing changes in perivascular nitric oxide (NO) and O2 concentration when a rat was exposed to 2.8 atmospheres absolute (ATA) O2. Vertical dashed lines show times for pressurization and decompression back to ambient pressure.
Source publication
We hypothesized that elevated partial pressures of O(2) would increase perivascular nitric oxide (*NO) synthesis. Rodents with O(2)- and.NO-specific microelectrodes implanted adjacent to the abdominal aorta were exposed to O(2) at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA). Exposures to 2.0 and 2.8 ATA O(2) stimulated neuronal (ty...
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... changes in tissue O 2 and NO elevations. A dual-barrel electrode placed adjacent to the wall of the abdominal aorta was used to examine the relationship between elevation of tissue O 2 tension and steady-state NO concentration. As shown in a representative ex- periment ( Fig. 1), tissue O 2 tension rose rapidly from a value between 10 and 40 Torr while air was breathed to a mean value of 1,900 Torr 100 (n 4) when rats were pressurized to 2.8 ATA while breathing pure O 2 . The steady-state NO concentration also increased rap- idly, and the mean concentration while O 2 was breathed at 1, 1.5, 2.0, and 2.8 ATA is ...
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... air- breathing rats (Fig. 8). A representative group of im- ages from Western blots is shown in Fig. 9. The eleva- tion of calmodulin-nNOS association was inhibited by treatment with geldanamycin but not by SOD. There was no significant increase in the association between HSP90 and nNOS among samples from rats exposed to 2.0 or 2.8 ATA O 2 (Figs. 9 and ...
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... 9. Representative group of images from Western blots after immunoprecipitation of aortic homogenates with antibody against nNOS shows calmodulin and HSP 90 coprecipitated with nNOS. Quantitative data are shown in Fig. 8. Where indicated, rats were injected with geldanamycin (0.3 mg/kg ip) or SOD (25,000 U/kg iv) before hyperbaric oxygen exposure. Fig. 10. Results from immunoprecipitation of aortic homogenates performed with antibody against nNOS. Band volumes were as- sessed on blots probed with anti-HSP90 and anti-nNOS and normal- ized to the band density obtained for the precipitated nNOS. Where indicated, rats were injected with geldanamycin (0.3 mg/kg ip) or SOD (25,000 U/kg iv) ...
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... to 2.8 ATA O 2 in aortic homogenates immu- noprecipitated with anti-eNOS (Table 2). A represen- tative group of images from Western blots is shown in Fig. 11. Akt protein kinase-dependent phosphorylation will activate eNOS by phosphorylating serine-1177 (10,13). There was no difference in the ratio of phosphor- ylated eNOS to total eNOS on Western blots of aortic homogenates probed with an antibody that recognizes serine-1177-phosphorylated eNOS (Table 2 and Fig. 11). Blots were also probed ...
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... from Western blots is shown in Fig. 11. Akt protein kinase-dependent phosphorylation will activate eNOS by phosphorylating serine-1177 (10,13). There was no difference in the ratio of phosphor- ylated eNOS to total eNOS on Western blots of aortic homogenates probed with an antibody that recognizes serine-1177-phosphorylated eNOS (Table 2 and Fig. 11). Blots were also probed for Akt and its activated form phospho-Akt. The ratio of phosphorylated Akt to total Akt was 0.5 0.2 (n 4) for aortic homogenates from control rats and 0.48 0.2 (n 4) for samples from rats exposed to 2.8 ATA O 2 (no significant differ- ...
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... and 4.4 0.4 (n 6, no significant differ- ence versus control) after 2.8 ATA O 2 . The limit of detection for this assay was 0.5 M, so a more sen- sitive technique was sought. We developed an EPR method by using erythrocyte lysates from which NO was extracted using the spin trap MGD (see MATERIALS AND METHODS). Examples of NO-MGD EPR spectra ob- Fig. 11. Representative group of images from Western blots probed for eNOS and phosphorylated eNOS (bottom) or blots probed for HSP90 and calmodulin after immunoprecipitation of aortic homog- enates with antibody against eNOS (top). Top portion shows calmod- ulin and HSP90 coprecipitated with nNOS. Fig. 12. Examples of electron paramagnetic ...
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... AND METHODS). Examples of NO-MGD EPR spectra ob- Fig. 11. Representative group of images from Western blots probed for eNOS and phosphorylated eNOS (bottom) or blots probed for HSP90 and calmodulin after immunoprecipitation of aortic homog- enates with antibody against eNOS (top). Top portion shows calmod- ulin and HSP90 coprecipitated with nNOS. Fig. 12. Examples of electron paramagnetic resonance spectra of methyl-D-glucamine dithiocarbamate (MGD)-NO spin adducts for different experiments. A: control, air-breathing rat; B: after exposure to 2.8 ATA O2 for 45 min; C: after exposure to 2.8 ATA while breathing 7.46% O2 (normoxic control); D: rat injected with L-NAME and then exposed to ...
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... experiments. A: control, air-breathing rat; B: after exposure to 2.8 ATA O2 for 45 min; C: after exposure to 2.8 ATA while breathing 7.46% O2 (normoxic control); D: rat injected with L-NAME and then exposed to 2.8 ATA O2 for 45 min. tained from control rats and rats exposed to 2.8 ATA using either pure O 2 or hypoxic gas (7.46% O 2 ) are shown in Fig. 12. Where indicated, rats were pre- treated with L-NAME. Approximately a 50% increase in spin concentration occurred with exposure to 2.8 ATA O 2 but not by exposure to normoxic gas at 2.8 ATA or in rats infused with L-NAME before exposure to 2.8 ATA O 2 ( Table 3). The NO concentration in erythro- cyte lysates was estimated by ...
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... was no significant increase in the association between nNOS and HSP90 in aortic preparations from rats exposed to 2.8 ATA O 2 (Fig. 10). This is different from observations in the brain, where exposure to 2.8 ATA O 2 has been shown to elevate NO synthesis by stimulating nNOS activity. In the brain, the associa- tion between HSP90 and nNOS was increased by 2.8 ATA O 2 , but there was no significant increase in the association between calmodulin and nNOS (42). This ...
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Citations
... Based on in-vitro studies, nitrous oxide plays a major role in bone marrow mobilization and endothelial progenitor cell release. Hyperbaric oxygen therapy (HBOT) increases nitrous oxide in cerebral cortex tissue, pulmonary tissue, and neutrophils, in turn increasing circulating progenitor cells, CD34, and myeloid marker cluster of differentiation 14 (CD14) [23][24][25][26]. Hence, HBOT is safe to enhance the mobilization of bone marrow (BM) derived progenitor cells into the circulation with minimal side effects ...
Critical limb ischemia (CLI), a serious outcome of peripheral artery disease, is frequently associated with morbid outcomes. The available treatment modalities do not provide satisfactory results, leading to marked morbidities such as joint contracture and amputations, resulting in a high economic burden. The peripheral vascular disease tends to cause more morbidity in patients with diabetes and atherosclerosis, given the preexisting compromised perfusion of medium and small vessels in diabetic patients. With surgical procedures, the chance of vascular compromise further increases, inducing a significantly greater rate of amputation. Hence, the need for nonsurgical treatment modalities such as stem cell therapy (SCT), which promotes angiogenesis, is warranted. In CLI, SCT acts through neovascularization and the development of collateral arteries, which increases blood supply to the soft tissues of the ischemic limb, providing satisfactory outcomes. An electronic database search was performed in PubMed, SCOPUS, EMBASE, and ScienceDirect to identify published clinical trial data, research studies, and review articles on stem cell therapy in critical limb ischemia. The search resulted in a total of 2391 results. Duplicate articles screening resulted in 565 articles. In-depth screening of abstracts and research titles excluded 520 articles, yielding 45 articles suitable for full-text review. On review of full text, articles with overlapping and similar results were filtered, ending in 25 articles. SCT promotes arteriogenesis, and bone marrow-derived mesenchymal stromal cells produce significant effects like reduced morbidity, improved amputation-free survival (AFS ) rate, and improved distal perfusion even in "no-option" CLI patients. SCT is a promising treatment modality for CLI patients, even in those in whom endovascular and revascularization procedures are impossible. SCT assures a prolonged AFS rate, improved distal perfusion, improved walking distances, reduced amputation rates, and increased survival ratio, and is well-tolerated.
... The mechanism of hyperbaric air SPC mobilization in this experiment is beyond the scope of this study, but may be similar to SPC mobilization found in hyperbaric oxygen therapy, which activates nitric oxide synthase and plays a prime role in initiating CD34 + SPC mobilization (30)(31)(32)(33). (CD34 background) CD34 + adult stem/ progenitor cells are a group of specific cell types that possess the abilities of self-renewal and multipotent differentiation (34,35). ...
Introduction
Hyperbaric air (HBA) was first used pharmaceutically in 1662 to treat lung disease. Extensive use in Europe and North America followed throughout the 19th century to treat pulmonary and neurological disorders. HBA reached its zenith in the early 20th century when cyanotic, moribund “Spanish flu pandemic” patients turned normal color and regained consciousness within minutes after HBA treatment. Since that time the 78% Nitrogen fraction in HBA has been completely displaced by 100% oxygen to create the modern pharmaceutical hyperbaric oxygen therapy (HBOT), a powerful treatment that is FDA approved for multiple indications. Current belief purports oxygen as the active element mobilizing stem progenitor cells (SPCs) in HBOT, but hyperbaric air, which increases tensions of both oxygen and nitrogen, has been untested until now. In this study we test HBA for SPC mobilization, cytokine and chemokine expression, and complete blood count.
Methods
Ten 34–35-year-old healthy volunteers were exposed to 1.27ATA (4 psig/965 mmHg) room air for 90 min, M-F, for 10 exposures over 2-weeks. Venous blood samples were taken: (1) prior to the first exposure (served as the control for each subject), (2) directly after the first exposure (to measure the acute effect), (3) immediately prior to the ninth exposure (to measure the chronic effect), and (4) 3 days after the completion of tenth/final exposure (to assess durability). SPCs were gated by blinded scientists using Flow Cytometry.
Results
SPCs (CD45dim/CD34⁺/CD133⁻) were mobilized by nearly two-fold following 9 exposures (p = 0.02) increasing to three-fold 72-h post completion of the final (10th) exposure (p = 0.008) confirming durability.
Discussion
This research demonstrates that SPCs are mobilized, and cytokines are modulated by hyperbaric air. HBA likely is a therapeutic treatment. Previously published research using HBA placebos should be re-evaluated to reflect a dose treatment finding rather than finding a placebo effect. Our findings of SPC mobilization by HBA support further investigation into hyperbaric air as a pharmaceutical/therapy.
... Another O 2 free radical produced as part of normal physiology is nitric oxide (NO). Hyperoxia increases the activity of all three NO Synthase isoforms (iNOS: inducible; eNOS: endothelial; and nNOS: neuronal) via several mechanisms [18,19]. NO seems to play a vital role in decompression stress, but the specific interactions during saturation diving are still unknown. ...
Saturation diving allows divers to reduce the risk of decompression sickness while working at depth for prolonged periods but may increase reactive oxygen species (ROS) production. Such modifications can affect endothelial function by exacerbating oxidative stress. This study investigated the effects of saturation diving on oxidative stress damage. Redox status was evaluated through: ROS production; total antioxidant capacity (TAC); nitric oxide metabolites (NOx); nitrotyrosine (3-NT); and lipid peroxidation (8-iso-PGF2α) assessment. Creatinine and neopterin were analyzed as markers of renal function and damage. Measurements were performed on saliva and urine samples obtained at four time points: pre; deep; post; and 24 h post. Four divers were included in the study. After the saturation dive (post), significant (p < 0.05) increases in ROS (0.12 ± 0.03 vs. 0.36 ± 0.06 µmol.min −1), TAC (1.88 ± 0.03 vs. 2.01 ± 0.08 mM), NOx (207.0 ± 103.3 vs. 441.8 ± 97.3 µM), 3-NT (43.32 ± 18.03 vs. 18.64 ± 7.45 nM·L −1), and 8-iso-PGF2α (249.7 ± 45.1 vs. 371.9 ± 54.9 pg·mg −1 creatinine) were detected. Markers of renal damage were increased as well after the end of the saturation dive (creatinine 0.54 ± 0.22 vs. 2.72 ± 1.12 g-L −1 ; neopterin 73.3 ± 27.9 vs. 174.3 ± 20.53 µmol·mol −1 creatinine). These results could ameliorate commercial or military diving protocols or improve the understanding of symptoms caused by oxygen level elevation.
... The absence of a statistically significant increase in serum NO concentrations can be interpreted by prolonged exposure to hyperbaric conditions, oxidative stress, and enhanced generation of superoxide anions responsible for neutralizing NO molecules [28][29][30][31]. This claim is supported by the observed decrease in serum NO concentrations after HBOT in patients with the highest disease stage (Fontain stage IV), where local inflammatory status is exacerbated by oxidative stress responsible for neutralizing NO molecules [30,32]. ...
... This is a safe, non-invasive method approved by the United States Food and Drug Administration for systemic mobilization of EPCs from their niche. HBO increases NO levels in perivascular tissues by stimulating nitric oxide synthase (NOS) and enhancing wound healing via NOmediated mobilization of EPCs from bone marrow [123,124]. Abidia et al. reported HBO treatment of patients with diabetic ischemia with non-healing lower extremities resulted in an enhanced wound closure by complete re-epithelialization [125]. ...
Despite advancements in wound care, healing of chronic diabetic wounds remains a great challenge for the clinical fraternity because of the intricacies of the healing process. Due to the limitations of existing treatment strategies for chronic wounds, stem/progenitor cell transplantation therapies have been explored as an alternative for tissue regeneration at the wound site. The non-healing phenotype of chronic wounds is directly associated with lack of vascularization. Therefore, endothelial progenitor cell (EPC) transplantation is proving to be a promising approach for the treatment of hypo-vascular chronic wounds. With the existing knowledge in EPC biology, significant efforts have been made to enrich EPCs at the chronic wound site, generating EPCs from somatic cells, induced pluripotent stem cells (iPSCs) using transcription factors, or from adult stem cells using chemicals/drugs for use in transplantation, as well as modulating the endogenous dysfunctional/compromised EPCs under diabetic conditions. This review mainly focuses on the pre-clinical and clinical approaches undertaken to date with EPC-based translational therapy for chronic diabetic as well as non-diabetic wounds to evaluate their vascularity-mediated regeneration potential.
... Several investigators have examined the effect of hyperoxia on the NOS enzymes and NO generation both in animal and cell models [38][39][40][41][42][43]. The studies are, however, inconsistent with respect to the direction of the effect on NO generation. ...
... The studies are, however, inconsistent with respect to the direction of the effect on NO generation. Some indicate increased NO generation after hyperoxic exposure [38][39][40], some report the opposite [41,42], and some report no effect at all [43]. ...
Nitric oxide (NO) may protect against gas bubble formation and risk of decompression sickness. We have previously shown that the crucial co-factor tetrahydrobiopterin (BH4) is oxidized in a dose-dependent manner when exposed to hyperoxia similar to diving conditions but with minor effects on the NO production by nitric oxide synthase. By manipulating the intracellular redox state, we further investigated the relationship between BH4 levels and production of NO in human endothelial cells (HUVECs). HUVECs were cultured with and without ascorbic acid (AA) and the glutathione (GSH) synthesis inhibitor buthionine sulfoximine, prior to hyperoxic exposure. The levels of biopterins and GSH were determined in cell lysates while the production of NO was determined in intact cells. Omitting AA resulted in a 91% decrease in BH4 levels (0.49 ± 0.08 to 0.04 ± 0.01 pmol/10⁶ cells, p⟨0.001) at 20 kPa oxygen (O2), and 88% decrease (0.24 ± 0.03 to 0.03 ± 0.01 pmol/10⁶ cells, p=0.01) after exposure to 60 kPa O2. The NO generation was decreased by 23% (74.5 ± 2.2 to 57.3 ± 5.6 pmol/min/mg protein, p⟨0.001) at 20 kPa O2, but no significant change was observed at 60 kPa O2. GSH depletion had no effects on the NO generation. No correlation was found between NO generation and the corresponding intracellular BH4 concentration (p=0.675, r=-0.055) or the BH4 to BH2 ratio (p=0.983, r=0.003), determined across 18 in vitro experiments. Decreased BH4 in HUVECs, due to hyperoxia or lack of ascorbic acid, does not imply corresponding decreases in NO generation.
... O modo de ação desta terapia é descrito por Thom (2009) O efeito imediato da oxigenoterapia hiperbárica é a hiperoxigenação que resulta do aumento do oxigênio dissolvido no plasma; o qual é diretamente proporcional à pressão parcial do oxigênio inalado Bassett & Bennett (1977). Um dos efeitos da OHB é o da melhoria da perfusão microvascular, provavelmente relacionado com um estímulo á síntese de óxido nitroso pelo oxigênio hiperbárico (Thom et al. 2003). ...
Corneal ulcerative keratitis is one of the most common causes of eye disease that causes loss of vision in dogs. Its etiology includes several types of trauma, inadequate lacrimal production, chemical lesions and eyelid defects, among others. The cornea is a non-vascularized, translucent structure, histologically composed of the epithelium, stroma, descemet membrane and endothelium. The depth that the lesion reaches between these layers will determine the degree of symptoms such as discomfort and ocular pain, photophobia, blepharospasm, ocular discharge, epiphora and loss of corneal transparency, culminating in anterior synechia, endophthalmitis, previous chamber collapse, glaucoma and atrophy of the ciliary body. The feasibility of tissue repair, the technique to be employed and the time provided for the recovery of the corneal tissue are closely linked to the number of layers involved; ranging from days to months. Hyperbaric oxygen therapy is an innovative therapy for small animals that are kept inside a hermetically sealed chamber with 100% controlled oxygen supply for previously established periods of time and subjected to pressure levels above atmospheric pressure. Hyperbaric oxygen therapy has the potential to accelerate the wound healing process. The scarcity of reports on the use of hyperbaric oxygen therapy in the treatment of corneal ulcers justifies the literary description of this clinical case, thus contributing to a greater clarification of aspects related to pathophysiology, diagnosis and new possibilities of treatment of this pathology in veterinary and human medicine. This paper reports the case of a three year old male Pug dog with traumatic corneal ulcerative keratitis treated with hyperbaric oxygen therapy, with fast and completes healing in 20 treatments.
... HBOT did not alter the hydroxyproline level in the presented series, which we assume to be due to the number and duration of the sessions being insufficient. It is known that HBOT increases the nitric oxide levels in perivascular tissues via the stimulation of nitric oxide synthase 44,45 . No difference was detected between the groups with regard to the histopathologic values. ...
Background:
An increase in intra-abdominal pressure causes a decrease in the splanchnic blood flow and the intramucosal pH of the bowel, as well as increasing the risk of ischemia in the colon. The aim of the present study is to evaluate the effect of hyperbaric oxygen therapy (HBOT) on the ischemia caused by laparoscopy in colonic anastomosis in an experimental model of laparoscopic colonic surgery.
Materials and methods:
We divided 30 male Wistar albino rats into three groups: Group A was the control (open colon anastomosis); Group B received LCA (laparoscopic colon anastomosis); while Group C received both LCA and HBOT. Each group contained ten animals. We placed Group C (LCA and HBOT) in an experimental hyperbaric chamber into which we administered pure oxygen at 2.1 atmospheres absolute 100% oxygen for 60 min for ten consecutive days.
Results:
The anastomotic bursting pressure value was found to be higher in the open surgery group (226 ± 8.8) (Group A). The result for Group C (213 ± 27), which received HBOT, was better than that for Group B (197 ± 27). However, there was no statistically significant difference between Group B and Group C. Group A showed better healing than the other groups, while significant differences in the fibroblast proliferation scores were found between Groups A and B. In terms of tissue hydroxyproline levels, a significant difference was found between Groups A and B and between Groups A and C, but not between Groups B and C.
Conclusions:
HBOT increases the oxygen level in the injured tissue. Although HBOT might offer several advantages, it had only a limited effect on the healing of colonic anastomosis in rats with increased intra-abdominal pressure in our study.
Key words:
Anastomosis, Colon, Hyperbaric Oxygen Treatment, Oxidative Stress.
... Bone marrow (BM) derived EPC has been shown to act as a key cell involved in neovascularization and homes to peripheral tissue in response to ischemia [12]. Induction of hyperoxia via HBO treatment has been shown to increase NO levels in perivascular tissues and BM via a nitric oxide synthase (NOS)mediated mechanism, resulting in EPC release from the BM and homing to ischemia tissues [24][25][26]. EPCs themselves express and secrete SDF-1 and CXCR4 [27], thus HBO treatment could increase SDF-1 and CXCR4 expression. Salvucci et al demonstrated endothelial expression of SDF-1 and CXCR4 may be reduced by inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ [28]. ...
To determine whether Hyperbaric oxygen preconditioning (HBO-PC) promotes neovascularization by increasing Stromal cell derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in transplanted skin flaps of rats. The epigastric pedicle skin flap was established in a rat model. Rats were randomly assigned to the following five groups: 1) sham-operated group (SH); 2) ischemia followed by reperfusion 3 days postoperatively group (IR3d); 3) ischemia followed by reperfusion 5 days postoperatively group (IR5d); 4) hyperbaric oxygen preconditioning and ischemia followed by reperfusion 3 days postoperatively group (HBO-PC3d); and 5) hyperbaric oxygen preconditioning and ischemia followed by reperfusion 5 days postoperatively group(HBO-PC5d). For the groups receiving HBO-PC, animals underwent 1 hour of HBO at 2.0 ATA in 100% O2 twice per day for 3 days consecutively prior to surgery. After perfusion, Laser Doppler perfusion imaging (LDPI) was performed, and skin flap tissue samples were harvested for histological evaluation and western blot analysis. Perfusion was significantly improved in the HBO-PC groups compared with the IR groups on postoperative 3 and 5. Microvessel density (MVD) was significantly increased by HBO-PC compared with IR groups postoperatively. Western blot analysis revealed that SDF-1 and CXCR4 expression in the HBO-PC groups was significantly increased compared with IR groups. HBO-PC promoted neovascularization via increasing expression levels of SDF-1 and CXCR4 in transplanted skin flaps of rats.
... This latter theory has the most scientific support: hyperoxaemia leads to increased production of oxygen radicals, with the superoxide ion being considered responsible for most of the vascular effects. Superoxide is known to inactivate nitric oxide [52,53]. Four human studies have investigated the effect of hyperoxia on nitric oxide [34,38,51,54] with two supporting the theory that vasoconstriction occurs via superoxide inactivation of nitric oxide [34,51]. ...
... In other cases, where oxygen therapy is given, often using HBO, such as wound healing, osteonecrosis and compromised flaps and grafts, other mechanisms, mostly cellular, may be responsible [9,14]. Breathing greater than 1 ATA of oxygen increases production of both reactive oxygen species [8] and nitrogen species [53,63,64]. ...
Oxygen treatment has been a cornerstone of acute medical care for numerous pathological states. Initially, this was supported by the assumed need to avoid hypoxaemia and tissue hypoxia. Most acute treatment algorithms, therefore, recommended the liberal use of a high fraction of inspired oxygen, often without first confirming the presence of a hypoxic insult. However, recent physiological research has underlined the vasoconstrictor effects of hyperoxia on normal vasculature and, consequently, the risk of significant blood flow reduction to the at-risk tissue. Positive effects may be claimed simply by relief of an assumed local tissue hypoxia, such as in acute cardiovascular disease, brain ischaemia due to, for example, stroke or shock or carbon monoxide intoxication. However, in most situations, a generalized hypoxia is not the problem and a risk of negative hyperoxaemia-induced local vasoconstriction effects may instead be the reality. In preclinical studies, many important positive anti-inflammatory effects of both normobaric and hyperbaric oxygen have been repeatedly shown, often as surrogate end-points such as increases in gluthatione levels, reduced lipid peroxidation and neutrophil activation thus modifying ischaemia-reperfusion injury and also causing anti-apoptotic effects. However, in parallel, toxic effects of oxygen are also well known, including induced mucosal inflammation, pneumonitis and retrolental fibroplasia. Examining the available 'strong' clinical evidence, such as usually claimed for randomized controlled trials, few positive studies stand up to scrutiny and a number of trials have shown no effect or even been terminated early due to worse outcomes in the oxygen treatment arm. Recently, this has led to less aggressive approaches, even to not providing any supplemental oxygen, in several acute care settings, such as resuscitation of asphyxiated newborns, during acute myocardial infarction or after stroke or cardiac arrest. The safety of more advanced attempts to deliver increased oxygen levels to hypoxic or ischaemic tissues, such as with hyperbaric oxygen therapy, is therefore also being questioned. Here, we provide an overview of the present knowledge of the physiological effects of oxygen in relation to its therapeutic potential for different medical conditions, as well as considering the potential for harm. We conclude that the medical use of oxygen needs to be further examined in search of solid evidence of benefit in many of the current clinical settings in which it is routinely used.
