Oxidative Stress Response Kinetics after 60 Minutes at Different (1.4 ATA and 2.5 ATA) Hyperbaric Hyperoxia Exposures.

Hyperbaric oxygen therapy (HBOT) is a therapeutical approach based on exposure to pure oxygen in an augmented atmospheric pressure. Although it has been used for years, the exact kinetics of the reactive oxygen species (ROS) between different pressures of hyperbaric oxygen exposure are still not clearly evidenced. In this study, the metabolic responses of hyperbaric hyperoxia exposures for 1 h at 1.4 and 2.5 ATA were investigated. Fourteen healthy non-smoking subjects (2 females and 12 males, age: 37.3 ± 12.7 years old (mean ± SD), height: 176.3 ± 9.9 cm, and weight: 75.8 ± 17.7 kg) volunteered for this study. Blood samples were taken before and at 30 min, 2 h, 24 h, and 48 h after a 1 h hyperbaric hyperoxic exposure. The level of oxidation was evaluated by the rate of ROS production, nitric oxide metabolites (NOx), and the levels of isoprostane. Antioxidant reactions were assessed through measuring superoxide dismutase (SOD), catalase (CAT), cysteinylglycine, and glutathione (GSH). The inflammatory response was measured using interleukine-6, neopterin, and creatinine. A short (60 min) period of mild (1.4 ATA) and high (2.5 ATA) hyperbaric hyperoxia leads to a similar significant increase in the production of ROS and antioxidant reactions. Immunomodulation and inflammatory responses, on the contrary, respond proportionally to the hyperbaric oxygen dose. Further research is warranted on the dose and the inter-dose recovery time to optimize the potential therapeutic benefits of this promising intervention.

Varying Oxygen Partial Pressure Elicits Blood-Borne Microparticles Expressing Different Cell-Specific Proteins-Toward a Targeted Use of Oxygen?

Oxygen is a powerful trigger for cellular reactions, but there are few comparative investigations assessing the effects over a large range of partial pressures. We investigated a metabolic response to single exposures to either normobaric (10%, 15%, 30%, 100%) or hyperbaric (1.4 ATA, 2.5 ATA) oxygen. Forty-eight healthy subjects (32 males/16 females; age: 43.7 ± 13.4 years, height: 172.7 ± 10.07 cm; weight 68.4 ± 15.7 kg) were randomly assigned, and blood samples were taken before and 2 h after each exposure. Microparticles (MPs) expressing proteins specific to different cells were analyzed, including platelets (CD41), neutrophils (CD66b), endothelial cells (CD146), and microglia (TMEM). Phalloidin binding and thrombospondin-1 (TSP), which are related to neutrophil and platelet activation, respectively, were also analyzed. The responses were found to be different and sometimes opposite. Significant elevations were identified for MPs expressing CD41, CD66b, TMEM, and phalloidin binding in all conditions but for 1.4 ATA, which elicited significant decreases. Few changes were found for CD146 and TSP. Regarding OPB, further investigation is needed to fully understand the future applications of such findings.

Oxygen: A Stimulus, Not "Only" a Drug.

Depending on the oxygen partial pressure in a tissue, the therapeutic effect of oxygenation can vary from simple substance substitution up to hyperbaric oxygenation when breathing hyperbaric oxygen at 2.5-3.0 ATA. Surprisingly, new data showed that it is not only the oxygen supply that matters as even a minimal increase in the partial pressure of oxygen is efficient in triggering cellular reactions by eliciting the production of hypoxia-inducible factors and heat-shock proteins. Moreover, it was shown that extreme environments could also interact with the genome; in fact, epigenetics appears to play a major role in extreme environments and exercise, especially when changes in oxygen partial pressure are involved. Hyperbaric oxygen therapy is, essentially, "intermittent oxygen" exposure. We must investigate hyperbaric oxygen with a new paradigm of treating oxygen as a potent stimulus of the molecular network of reactions.

Oxidative Stress and Inflammation, MicroRNA, and Hemoglobin Variations after Administration of Oxygen at Different Pressures and Concentrations: A Randomized Trial.

Exercise generates reactive oxygen species (ROS), creating a redox imbalance towards oxidation when inadequately intense. Normobaric and hyperbaric oxygen (HBO) breathed while not exercising induces antioxidant enzymes expression, but literature is still poor. Twenty-two athletes were assigned to five groups: controls; 30%, or 50% O2; 100% O2 (HBO) at 1.5 or 2.5 atmosphere absolute (ATA). Twenty treatments were administered on non-training days. Biological samples were collected at T0 (baseline), T1 (end of treatments), and T2 (1 month after) to assess ROS, antioxidant capacity (TAC), lipid peroxidation, redox (amino-thiols) and inflammatory (IL-6, 10, TNF-α) status, renal function (i.e., neopterin), miRNA, and hemoglobin. At T1, O2 mixtures and HBO induced an increase of ROS, lipid peroxidation and decreased TAC, counterbalanced at T2. Furthermore, 50% O2 and HBO treatments determined a reduced state in T2. Neopterin concentration increased at T1 breathing 50% O2 and HBO at 2.5 ATA. The results suggest that 50% O2 treatment determined a reduced state in T2; HBO at 1.5 and 2.5 ATA similarly induced protective mechanisms against ROS, despite the latter could expose the body to higher ROS levels and neopterin concentrations. HBO resulted in increased Hb levels and contributed to immunomodulation by regulating interleukin and miRNA expression.

Hypoxic and Hyperoxic Breathing as a Complement to Low-Intensity Physical Exercise Programs: A Proof-of-Principle Study.

Inflammation is an adaptive response to both external and internal stimuli including infection, trauma, surgery, ischemia-reperfusion, or malignancy. A number of studies indicate that physical activity is an effective means of reducing acute systemic and low-level inflammation occurring in different pathological conditions and in the recovery phase after disease. As a proof-of-principle, we hypothesized that low-intensity workout performed under modified oxygen supply would elicit a "metabolic exercise" inducing a hormetic response, increasing the metabolic load and oxidative stress with the same overall effect expected after a higher intensity or charge exercise. Herein, we report the effect of a 5-week low-intensity, non-training, exercise program in a group of young healthy subjects in combination with the exposure to hyperoxia (30% and 100% pO2, respectively) or light hypoxia (15% pO2) during workout sessions on several inflammation and oxidative stress parameters, namely hemoglobin (Hb), redox state, nitric oxide metabolite (NOx), inducible nitric oxide synthase (iNOS), inflammatory cytokine expression (TNF-α, interleukin (IL)-6, IL-10), and renal functional biomarkers (creatinine, neopterin, and urates). We confirmed our previous reports demonstrating that intermittent hyperoxia induces the normobaric oxygen paradox (NOP), a response overlapping the exposure to hypoxia. Our data also suggest that the administration of modified air composition is an expedient complement to a light physical exercise program to achieve a significant modulation of inflammatory and immune parameters, including cytokines expression, iNOS activity, and oxidative stress parameters. This strategy can be of pivotal interest in all those conditions characterized by the inability to achieve a sufficient workload intensity, such as severe cardiovascular alterations and articular injuries failing to effectively gain a significant improvement of physical capacity.

Spirometry and oxidative stress after rebreather diving in warm water.

INTRODUCTION: Hyperbaric oxygen (HBO2) therapy and use of enriched air can result in oxidative injury affecting the brain, lungs and eyes. HBO2 exposure during diving can lead to a decrease in respiratory parameters. However, the possible effects of acute exposure to oxygen-enriched diving on subsequent spirometric performance and oxidative state in humans have not been recently described recently. We aim to investigate possible effects of acute (i) hyperbaric and (ii) hyperbaric hyperoxic exposure using scuba or closed-circuit rebreather (CCR) on subsequent spirometry and to assess the role of oxidative state after hyperoxic diving. METHODS: Spirometry and urine samples were obtained from six well-trained divers (males, mean ± SD, age: 43.33 ± 9.16 years; weight: 79.00 ± 4.90 kg; height: 1.77 ± 0.07 meters) before (CTRL) and after a dive breathing air, and after a dive using CCR (PO2 1.4). In the crossover design (two dives separated by six hours) each subject performed a 20-minute session of light underwater exercise at a depth of 15 meters in warm water (31-32°C). We measured urinary 8-isoprostane and 8-OH-2-deoxyguanosine evaluating lipid and DNA oxidative damages. RESULTS: Different breathing conditions (air vs. CCR) did not significantly affect spirometry. A significant increase of 8-OH-dG (1.85 ± 0.66 vs. 4.35 ± 2.12; P ⟨ 0.05) and 8-isoprostane (1.35 ± 0.20 vs. 2.59 ± 0.61; P ⟨ 0.05) levels after CCR dive with respect to the CTRL was observed. Subjects did not have any ill effects during diving. CONCLUSIONS: Subjects using CCR showed elevated oxidative stress, but this did not correlate with a reduction in pulmonary function.

Preconditioning to Reduce Decompression Stress in Scuba Divers.

BACKGROUND: Using ultrasound imaging, vascular gas emboli (VGE) are observed after asymptomatic scuba dives and are considered a key element in the potential development of decompression sickness (DCS). Diving is also accompanied with vascular dysfunction, as measured by flow-mediated dilation (FMD). Previous studies showed significant intersubject variability to VGE for the same diving exposure and demonstrated that VGE can be reduced with even a single pre-dive intervention. Several preconditioning methods have been reported recently, seemingly acting either on VGE quantity or on endothelial inflammatory markers. METHODS: Nine male divers who consistently showed VGE postdive performed a standardized deep pool dive (33 m/108 ft, 20 min in 33°C water temperature) to investigate the effect of three different preconditioning interventions: heat exposure (a 30-min session of dry infrared sauna), whole-body vibration (a 30-min session on a vibration mattress), and dark chocolate ingestion (30 g of chocolate containing 86% cocoa). Dives were made one day per week and interventions were administered in a randomized order. RESULTS: These interventions were shown to selectively reduce VGE, FMD, or both compared to control dives. Vibration had an effect on VGE (39.54%, SEM 16.3%) but not on FMD postdive. Sauna had effects on both parameters (VGE: 26.64%, SEM 10.4%; FMD: 102.7%, SEM 2.1%), whereas chocolate only improved FMD (102.5%, SEM 1.7%). DISCUSSION: This experiment, which had the same subjects perform all control and preconditioning dives in wet but completely standardized diving conditions, demonstrates that endothelial dysfunction appears to not be solely related to VGE.Germonpré P, Balestra C. Preconditioning to reduce decompression stress in scuba divers. Aerosp Med Hum Perform. 2017; 88(2):114-120.

Hypothesis: the influence of cavitation or vacuum phenomenon for decompression sickness.

Dr Yanagawa and his colleagues present an interesting hypothesis, and our group has had some discussions around this vacuum phenomenon and decompression sickness (DCS). I am aware of at least one diver in whom symptoms appeared after a 'self-manipulation' of his lower lumbar spine. The diver exited the water symptom-free and approximately 1.5 hours after the dive went to the hotel swimming pool. Before getting into the water, he self manipulated his lumbar spine as he was in the habit of doing, provoking the familiar cracking sound. Some minutes after this, symptoms appeared and he went to the chamber for treatment. DCS was confirmed in the lumbar zone. Several hypotheses can be raised: the 'habitual' manipulations may have changed the tissue properties in that zone and facilitated inadequate desaturation; the symptoms would have appeared anyway despite any action; the low back pain was not DCS but another mechanical lesion that could be cured by the rapidly applied hyperbaric treatment, etc. We clearly understand that this episode can by no means confirm the hypothesis, it is just an observation, no objective link can be set nor, of course, eliminated.

The innervation of the axillary arch determined by surface stimulodetection electromyography.

The axillary arch (AA) is a muscular anatomical variation in the fossa axillaris that has been extensively studied in cadaveric specimens. Within these dissections, different innervations of the AA have been proposed, but this has never been explored in vivo. Knowledge of the innervation of the AA is required in order to better understand its function (e.g. predisposition for certain sports and/or activities, understanding shoulder injuries in overhead sports). Here, we report on the use of surface stimulodetection electromyography (SSEMG) to resolve the innervation of the AA in 20 subjects (12 women, eight men - mean age of 21.3 ± 2.7 years) with a uni- or bilateral AA. SSEMG of each muscle [M. latissimus dorsi (MLD) and M. pectoralis major] was performed with a four-channel electrostimulation measuring system in order to determine the innervation of the AA. The results showed co-contraction of the MLD in 85% of the subjects after AA stimulation. In the remaining subjects, no specific localized response was observed due to non-specific nerve stimulation, inherent to the proximity of the brachial plexus in these individuals. Our findings demonstrate that SSEMG exploration offers a practical and reliable tool for investigating anatomical aspects of muscle innervation in vivo. Using this approach, we conclude that the AA receives the same innervation as the MLD (the N. thoracodorsalis), and may be considered a muscular extension of the latter.

Supraorbital transcutaneous neurostimulation has sedative effects in healthy subjects.

BACKGROUND: Transcutaneous neurostimulation (TNS) at extracephalic sites is a well known treatment of pain. Thanks to recent technical progress, the Cefaly® device now also allows supraorbital TNS. During observational clinical studies, several patients reported decreased vigilance or even sleepiness during a session of supraorbital TNS. We decided therefore to explore in more detail the potential sedative effect of supraorbital TNS, using standardized psychophysical tests in healthy volunteers. METHODS: We performed a double-blind cross-over sham-controlled study on 30 healthy subjects. They underwent a series of 4 vigilance tests (Psychomotor Vigilance Task, Critical Flicker Fusion Frequency, Fatigue Visual Numeric Scale, d2 test). Each subject was tested under 4 different experimental conditions: without the neurostimulation device, with sham supraorbital TNS, with low frequency supraorbital TNS and with high frequency supraorbital TNS. RESULTS: As judged by the results of three tests (Psychomotor Vigilance Task, Critical Flicker Fusion Frequency, Fatigue Visual Numeric Scale) there was a statistically significant (p < 0.001) decrease in vigilance and attention during high frequency TNS, while there were no changes during the other experimental conditions. Similarly, performance on the d2 test was impaired during high frequency TNS, but this change was not statistically significant. CONCLUSION: Supraorbital high frequency TNS applied with the Cefaly® device decreases vigilance in healthy volunteers. Additional studies are needed to determine the duration of this effect, the underlying mechanisms and the possible relation with the stimulation parameters. Meanwhile, this effect opens interesting perspectives for the treatment of hyperarousal states and, possibly, insomnia.

Acupuncture effect on thermal tolerance and electrical pain threshold: a randomised controlled trial.

OBJECTIVE: The aim of this study was to test whether acupuncture could modify the threshold of tolerance to thermal and electrical stimuli. METHODS: A randomised placebo-controlled single-blind trial was conducted in 36 healthy volunteers randomly distributed to control (no treatment), conventional acupuncture and sham acupuncture groups. The subjects were blind to the group allocation. The authors measured before and after treatment the pain threshold with the Painmatcher (Cefar Medical AB, Lund, Sweden) and the cold tolerance with the cold pressor test, together with the Visual Analogue Scale pain score. RESULTS: Electrical stimulation threshold and cold pressor tolerance both increased significantly in the control and the true acupuncture groups, but not the sham group. The changes in the true acupuncture group were highly statistically significant and amounted to 24% (pain threshold) and 44% (cold tolerance) increases in threshold. The changes in the true group were significantly greater than the control group but not significantly different from the sham group. The changes in the sham and control groups were not significantly different from each other. CONCLUSION: Acupuncture at true, appropriate points was more effective than no intervention in raising pain threshold and tolerance in volunteers, and acupuncture at inappropriate points had an intermediate effect which was not significantly different from either. Thus acupuncture analgesia may not be a point specific effect.

Decompression illness medically reported by hyperbaric treatment facilities: cluster analysis of 1929 cases.

INTRODUCTION: The term decompression illness (DCI) describes maladies resulting from inadequate decompression, but there is little consensus concerning clinically useful DCI subclasses. Our aim was to explore an objective DCI classification using multivariate statistics to assess naturally associated clusters of DCI manifestations. We also evaluated their mapping onto other DCI classifications and investigated the association with therapeutic outcome. METHODS: We defined the optimal number of clusters using "two-step" cluster analysis and Bayesian information criterion with confirmation by hierarchical clustering with squared Euclidian distances and Ward's method. The data were 1929 DCI cases reported by hyperbaric chambers to the Divers Alert Network (DAN America) from 1999-2003. RESULTS: Four robust and highly significant clusters of DCI manifestations were demonstrated containing 300, 741, 333, and 555 patients. Each cluster had characteristic manifestations. Cluster 1 was effectively pain only. For Cluster 2, characteristic manifestations included numbness, paresthesia, and decreased skin sensitivity; for Cluster 3, malaise, paralysis, muscular weakness, and bladder-bowel dysfunction; and for Cluster 4, hearing loss, localized skin swelling, tinnitus, skin rash and mottling, confusion, dyspnea/chokes, muscular problems, vision problems, altered consciousness, headache, vertigo, nausea, fatigue, dizziness, and abnormal sensations. DISCUSSION: Internal reliability was confirmed by arbitrarily dividing the dataset into two parts and repeating the analysis. The clusters mapped poorly onto traditional DCI categories (AGE, Type I DCS, Type II DCS), but more specifically onto the Perceived Severity Index (PSI). All three classification methods (DCI, Cluster, PSI) predicted complete relief of manifestations equally well. We conclude that cluster analysis is an objective method for classifying DCI manifestations independent of clinical judgment.

Predive sauna and venous gas bubbles upon decompression from 400 kPa.

INTRODUCTION: This study investigated the influence of a far infrared-ray dry sauna-induced heat exposure before a simulated dive on bubble formation, and examined the concomitant adjustments in hemodynamic parameters. METHODS: There were 16 divers who were compressed in a hyperbaric chamber to 400 kPa (30 msw) for 25 min and decompressed at 100 kPa x min(-1) with a 4-min stop at 130 kPa. Each diver performed two dives 5 d apart, one with and one without a predive sauna session for 30 min at 65 degrees C ending 1 h prior to the dive. Circulating venous bubbles were detected with a precordial Doppler 20, 40, and 60 min after surfacing, at rest, and after flexions. Brachial artery flow mediated dilation (FMD), blood pressure, and bodyweight measurements were taken before and after the sauna session along with blood samples for analysis of plasma volume (PV), protein concentrations, plasma osmolality, and plasma HSP70. RESULTS: A single session of sauna ending 1 h prior to a simulated dive significantly reduced bubble formation [-27.2% (at rest) to 35.4% (after flexions)]. The sauna session led to an extracellular dehydration, resulting in hypovolemia (-2.7% PV) and -0.6% bodyweight loss. A significant rise of FMD and a reduction in systolic blood pressure and pulse pressure were observed. Plasma HSP70 significantly increased 2 h after sauna completion. CONCLUSION: A single predive sauna session significantly decreases circulating bubbles after a chamber dive. This may reduce the risk of decompression sickness. Sweat dehydration, HSP, and the NO pathway could be involved in this protective effect.

Serum erythropoietin levels in healthy humans after a short period of normobaric and hyperbaric oxygen breathing: the "normobaric oxygen paradox".

Renal (peritubular) tissue hypoxia is a well-known physiological trigger for erythropoietin (EPO) production. We investigated the effect of rebound relative hypoxia after hyperoxia obtained under normo- and hyperbaric oxygen breathing conditions. A group of 16 healthy volunteers were investigated before and after a period of breathing 100% normobaric oxygen for 2 h and a period of breathing 100% oxygen at 2.5 ATA for 90 min (hyperbaric oxygen). Serum EPO concentration was measured using a radioimmunoassay at various time points during 24-36 h. A 60% increase (P < 0.001) in serum EPO was observed 36 h after normobaric oxygen. In contrast, a 53% decrease in serum EPO was observed at 24 h after hyperbaric oxygen. Those changes were not related to the circadian rhythm of serum EPO of the subjects. These results indicate that a sudden and sustained decrease in tissue oxygen tension, even above hypoxia thresholds (e.g., after a period of normobaric oxygen breathing), may act as a trigger for EPO serum level. This EPO trigger, the "normobaric oxygen paradox," does not appear to be present after hyperbaric oxygen breathing.