Evaluation of energy metabolism and physical work capacity of divers for determining the optimal oxygen level during breathing gas mixture under pressure up to 5.1 MPa]

A complex evaluation of energy metabolism, oxygen-transport function of blood and physical work capacity of aquanauts has been performed during three imitation divings at depths of 400, 450 and 500 m in heliox as a breathing medium. These experiments have shown that optimal levels of partial oxygen pressure in artificial chamber environment are 30-33 kPa at 4.1 MPa, 32-35 kPa at 4.6 MPa and 33-34 kPa at 5.1 MPa. It is established that 24-days exposure of aquanautes to 4.6 MPa and 10-days exposure to 5.1 MPa yield no unfavourable changes of the examined organism functions. The activated lipid exchange in combination with stable carbohydrate catabolism, the elevated levels of oxygen consumption and its partial pressure in blood and transient fluctuations of erythropoiesis activity are interpreted as compensatory responses of diverse organisms under the influence of hyperbaric factors.     

Suppression of humoral antibody synthesis on exposure to hyperbaric oxygenation

The influence of hyperbaric oxygenation (HBO) on the immune response in mice, immunized intraperitoneally with sheep red blood cells, was studied. HBO was shown to reduce hemagglutinin and hemolysin titres in peripheral blood as well as to decrease the amount of antibody-forming cells in the spleen. The most pronounced immunodepressant HBO effect is seen when hyperbaric oxygenation is carried out under toxic conditions before immunization of the animals with low antigen doses. Relationship is shown between the immunodepressant HBO effect and reduced leucocyte and lymphocyte counts in peripheral blood of the animals.     

Various mechanisms of regulation of lipid peroxidation in human erythrocytes after long-term exposure to hyperbaric oxygenation]

Intensity of lipid peroxidation and activity of antioxidant protection enzymes in erythrocytes were measured in three experiments with 10-24 days exposure of aquanauts under 4.6 and 5.1 MPa. It is established that there is no pathological intensification of lipid peroxidation when oxygen partial pressure in breathing gas mixture is optimal. This process is under reliable control by modulation of antioxidant enzymes activity. The high sensitivity of these research methods allows using them to determine exposure limitations under high pressure and optimal oxygen concentrations in breathing gas mixture.     

Effects of hyperbaric oxygenation on activation of immunocompetent cells and lipid peroxidation under immunization by heterologous erythrocytes]

On the basis of rats' experiments under conditions of HBO a close relationship was established between the intensity of immune processes and peroxide oxidation of lipids (POL). The study enabled to show a connection between immunoreactivity stimulation in spleen cells and certain levels of POL intensity and anti-oxidation protection as well. There were assessed diverse HBO effects on intact and immune organism and hyperbaric dependence of immunodepression on POL's intensification.     

Hyperbaric oxygenation in the comprehensive therapy of patients with rheumatoid arthritis (clinico-immunologic study)

For 35 of 50 patients with rheumatoid arthritis traditional drug therapy was a minor success for a long time. Without any modifications of the drug therapy every patient went through a course of hyperbaric oxygenation (HBO): 21 sessions under 1.7 ata for 40 min. Good clinical results both immediate and remote have been obtained. The effect of HBO on the immune system of the patients has intensified the suppressive function of T-lymphocytes (especially with systemic symptoms of the disease), normalized cell-bound immunity and decreased the serum concentration in immune complexes.     

Effects of Hyperbaric Oxygen at 1.25 Atmospheres Absolute with Normal Air on Macrophage Number and Infiltration during Rat Skeletal Muscle Regeneration

Use of mild hyperbaric oxygen less than 2 atmospheres absolute (2026.54 hPa) with normal air is emerging as a common complementary treatment for severe muscle injury. Although hyperbaric oxygen at over 2 atmospheres absolute with 100% O₂ promotes healing of skeletal muscle injury, it is not clear whether mild hyperbaric oxygen is equally effective. The purpose of the present study was to investigate the impact of hyperbaric oxygen at 1.25 atmospheres absolute (1266.59 hPa) with normal air on muscle regeneration. The tibialis anterior muscle of male Wistar rats was injured by injection of bupivacaine hydrochloride, and rats were randomly assigned to a hyperbaric oxygen experimental group or to a non-hyperbaric oxygen control group. Immediately after the injection, rats were exposed to hyperbaric oxygen, and the treatment was continued for 28 days. The cross-sectional area of centrally nucleated muscle fibers was significantly larger in rats exposed to hyperbaric oxygen than in controls 5 and 7 days after injury. The number of CD68- or CD68- and CD206-positive cells was significantly higher in rats exposed to hyperbaric oxygen than in controls 24 h after injury. Additionally, tumor necrosis factor-α and interleukin-10 mRNA expression levels were significantly higher in rats exposed to hyperbaric oxygen than in controls 24 h after injury. The number of Pax7- and MyoD- or MyoD- and myogenin-positive nuclei per mm² and the expression levels of these proteins were significantly higher in rats exposed to hyperbaric oxygen than in controls 5 days after injury. These results suggest that mild hyperbaric oxygen promotes skeletal muscle regeneration in the early phase after injury, possibly due to reduced hypoxic conditions leading to accelerated macrophage infiltration and phenotype transition. In conclusion, mild hyperbaric oxygen less than 2 atmospheres absolute with normal air is an appropriate support therapy for severe muscle injuries.     

Effect of hyperoxia on the immune status of oxygen divers and endurance athletes

Physical activity, particularly that, exerted by endurance athletes, impacts the immune status of the human body. Prolonged duration and high-intensity endurance training lead to increased production of reactive oxygen species (ROS) and thereby to oxidative stress. Military combat swimmers (O₂-divers) are regularly exposed to hyperbaric hyperoxia (HBO) in addition to intensive endurance training intervals. They are, therefore, exposed to extreme levels of oxidative stress. Several studies support that the intensity of oxidative stress essentially determines the effect on immune status. The aim of this study was to comparatively characterise peripheral blood mononuclear cells (PBMCs) of O₂-divers (military combat swimmers), endurance athletes (amateur triathletes), and healthy control volunteers with respect to DNA fragmentation, immune status and signs of inflammation. Furthermore, it was investigated how PBMCs from these groups responded acutely to exposure to HBO. We showed that DNA fragmentation was comparable in PBMCs of all three groups under basal conditions directly after HBO exposure. However, significantly higher DNA fragmentation was observed in O₂-divers 18?hours after HBO, possibly indicating a slower recovery. O₂-divers also exhibited a proinflammatory immune status exemplified by an elevated number of CD4⁺CD25⁺ T cells, elevated expression of proinflammatory cytokine IL-12, and diminished expression of anti-inflammatory TGF-β1 compared to controls. Supported by a decreased basal gene expression and prolonged upregulation of anti-oxidative HO-1, these data suggest that higher oxidative stress levels, as present under intermitted hyperbaric hyperoxia, e.g. through oxygen diving, promote a higher inflammatory immune status than oxidative stress through endurance training alone.     

Immunomodulatory effect of oxygen and pressure

The immunomodulatory effect of hyperbaric oxygen, involving altered cytokine release by macrophages, is well described. Importantly, however, it is not known what the relative contribution is of the hyperbaric environment of the cells vs. increased oxygen tension on these hyperbaric oxygen-dependent effects. We compared, therefore, cytokine release by murine macrophages under hyperbaric oxygen, hyperpressure of normal air and normobaric conditions. We observed that hyperbaric oxygen enhanced cytokine release of both unstimulated as well as lipopolysaccharide (LPS)-challenged macrophages. Hyperpressure of normal air, however, enhanced LPS-induced cytokine production but did not elicit cytokine release in unstimulated macrophages. To further investigate the molecular details underlying the effects of hyperbaric oxygen, we investigated the effect of the p42/p44 mitogen-activated protein (MAP) kinase inhibitor PD98059 and the p38 MAP kinase inhibitor SB203580. Neither inhibitor, however, had a significant effect on the modulatory effects of hyperbaric oxygen on cytokine release. We concluded that the immunomodulatory effect of hyperbaric oxygen contains a component for which hyperpressure is sufficient and a component that apart from hyperpressure also requires hyperoxygenation.     

Expanding the limits of composite grafting: a case report of successful nose replantation assisted by hyperbaric oxygen therapy

A successful nose replantation assisted by hyperbaric oxygen therapy is presented, with a brief discussion of the possible mechanisms and a brief literature review of the use of hyperbaric oxygen in tissue preservation and replantation. Although it is not certain that the hyperbaric oxygenation ensured the survival of the replanted nose in this 2-year-old girl, there was documented change in graft appearance during the initial hyperbaric oxygen treatment. A 1-month, 1-year, and 2-year follow-up is included.     

高压氧对正常及SIRS大鼠脾T淋巴细胞的影响

本实验以SIRS为基础,以免疫功能和炎症反应中具有代表性的脾T淋巴细胞为研究对象,观察高压氧对正常机体以及SIRS状态机体的影响并探讨其可能的机制。健康雄性SD大鼠40只,体重约140~180 g,随机分为5组,每组8只。A组：腹腔注射生理盐水（5 mL/kg）;B组：腹腔注射等量生理盐水,做3次高压氧;C组：腹腔注射酵母多糖-石蜡悬液（500 mg/kg）;D组：腹腔注射酵母多糖-石蜡悬液（500 mg/kg）,做1次高压氧治疗;E组：腹腔注射酵母多糖-石蜡悬液（500 mg/kg）,做3次高压氧治疗。采用流式细胞仪计算大鼠脾脏淋巴细胞数量及比例。高压氧治疗（B组）降低正常大鼠外周血CD4＋T细胞百分比（P〈0.01）,对CD8＋T细胞无影响,因此CD4＋/CD8＋T细胞比值下降（P〈0.05）。酵母多糖腹腔注射（C组）使大鼠外周血CD4＋、CD8＋T细胞均减少（P〈0.01）,但CD4＋/CD8＋T细胞比值不变。1次和3次HBO治疗（D和E组）可使酵母多糖所致CD4＋T细胞减少（C组）明显恢复（P〈0.01,P〈0.05）,故CD3＋CD4＋/CD3＋CD8＋比值升高（P〈0.01,P〈0.05）,HBO几乎不影响CD8＋T细胞比例（P〉0.05）。酵母多糖导致大鼠脾脏CD4＋和CD8＋T细胞比例减少;高压氧可减少正常大鼠脾脏CD4＋T细胞比例,而增加SIRS脾脏的CD4＋T细胞比例,而对CD8＋T细胞无影响。     

Vitamin C prevents hyperbaric oxygen-induced growth retardation and lipid peroxidation and attenuates the oxidation-induced up-regulation of glutathione in guinea pigs

Hyperbaric oxygen therapy is used to treat various clinical conditions, but it also causes oxidative damage. The objectives of this study are to determine if increased vitamin C intake can prevent hyperbaric oxygen-induced damage and to determine interactions among vitamin C, glutathione and vitamin E in response to oxidative stress. The growth rates of unexposed guinea pigs fed 1.25 mg vitamin C/day were indistinguishable from that of guinea pigs fed 50 mg vitamin C/day. In contrast, hyperbaric oxygen exposure resulted in growth retardation in guinea pigs fed 1.25 mg vitamin C/day, but it had little effect on the growth rates of guinea pigs fed 50 mg vitamin C/day. Increased vitamin C intake also prevented hyperbaric oxygen-induced lipid peroxidation in the liver. In guinea pigs not exposed to hyperbaric oxygen, levels of vitamin C in tissues were closely related to vitamin C intake, but tissue levels of glutathione and vitamin E were not related to vitamin C intake. However, interactions between vitamin C and glutathione were observed upon chronic hyperbaric oxygen exposure. Chronic hyperbaric oxygen exposure resulted in >2-fold increases in the levels of glutathione in liver and lung of guinea pigs fed 1.25 mg vitamin C/day. In comparison, the oxidation-induced increases in glutathione were significantly attenuated in guinea pigs fed 50 mg vitamin C/day. These data show that increased intake of vitamin C can prevent or alleviate the hyperbaric oxygen-induced damage. The interactions between vitamin C and glutathione upon hyperbaric oxygen exposure indicate that there is a homeostatic regulation of antioxidant capacity in guinea pig tissues.     

Experiments on the effects of hyperbaric oxygen on flap survival in the pig

The use of hyperbaric oxygen has been advocated as a method of improving survival of ischemic flaps. Experiments were done in the pig using modern flap designs and hyperbaric oxygen protocols that have been reported to be effective in rodents. The results of these experiments indicate that hyperbaric oxygen is not effective in improving flap survival in the pig.     

Adaptive reactions in humans during repeated exposure to deep-water saturation immersion]

Evaluation of changes in respiration circulation and respiratory gas transport has shown that long-term influence of hyperbaria gives rise to phase changes and promotes a shift to a new level of the functional state of aquanauts. It is established that the postdecompression syndrome is characterized by the lability of main parameters of breathing and circulation, depression of gas exchange, disorders of bronchial permeability, relaxation of the cardiac pump function, decrease of physical workability against the background of inhibition of the adrenal cortex and weakening of the non-specific immunoresistance. Examination of 145 deep divers has revealed regularities of readaptation dynamics and has permitted a conclusion on an increase of unfavourable tendencies in the ventilatory pulmonary function and cardiac pump function under repeated effect of saturated diving. The normative values of external respiration are worked out as applied to divers. Some new approaches to the technology of medical providing of deep divings and correction of non-specific professional pathology of acquanauts are physiologically substantiated proceeding from tendencies of shifts in the periods between divings and diving norms.     

高压氧暴露大鼠肺组织内PPAR通路分子变化规律

目的:研究高压氧暴露大鼠肺组织内过氧化物酶体增殖因子活化受体(PPAR)通路分子表达变化规律。方法:27只雄性SD大鼠随机分为高压常氧对照组(0.23 MPa空气)、高压氧时间序列处理组(0.23 MPa纯氧,分别暴露2 h、4 h、6 h和8 h),持续小流量通风,维持舱内O2浓度>99%。应用HE染色观察各组大鼠肺组织形态学变化;应用oligo芯片检测各个时间表达谱;应用RT-PCR验证发生改变的部分PPAR通路基因。结果:与高压常氧对照组相比,高压氧时间序列处理组造成的肺损伤逐渐加重;表达谱芯片的基因本体论(Go)富集分析结果中有一类PPAR通路类,包含有多个PPAR通路分子;RT-PCR结果提示PPARδ-和PPARγ-均在较长时间高压氧暴露的肺组织中上调。结论:高压氧长时间暴露造成的肺型氧中毒可引起PPAR通路的激活。     

Hyperbaric oxygen toxicity and ribosome destruction in Escherichia coli K12

The viability of resting suspensions of Escherichia coli K12 Ymel exposed to air plus 300 psi (1 psi = 6.895 kPa) oxygen (hyperbaric oxygen) decreased as an apparent first-order process after an initial period of constant viability. Control suspensions exposed to air plus 300 psi nitrogen (hyperbaric nitrogen) did not lose viability over the 96 h of the experiment. It was observed that a decrease in the refractive index of the cells preceded the loss of viability in hyperbaric oxygen. This finding together with electron micrographs, which showed extensive loss of ribosomal particles in bacteria incubated in hyperbaric oxygen, led us to suspect that ribosome injury or disassociation might be important in hyperbaric oxygen toxicity. In support of this we found that cellular RNA, labeled with [5-3H]uridine, was much more rapidly and more completely degraded in hyperbaric oxygen than in hyperbaric nitrogen. Furthermore, a far greater proportion of RNA was degraded than was DNA or protein. A direct assay for ribosome particles by sucrose gradient centrifugation showed that only 34% of the 70S ribosome particles was lost during the first 24 h in hyperbaric nitrogen whereas in hyperbaric oxygen 99.6% of the 70S particles was degraded during the same period. In hyperbaric oxygen the rate of viability loss between 24 and 72 h was equal to the rate of 70S ribosome degradation during the first 24 h. If 70S ribosome disassociation in hyperbaric oxygen continues at the same rate after first 24 h, then cumulative 70S ribosome disassociation or injury may lead to and provide an explanation for irreversible bacterial cell injury and the loss of viability.     

Changes in cardiac rhythm in humans during breathing compressed air under pressure up to 1.1 MPa (results of the rhythmo-cardiographic study)]

Dynamics of cardiac rhythm has been considered according to rhythmocardiographic characteristics of heart rate under orthostatic test and one-stage step-test in four altitude chamber experiments where air under pressure of 0.4-1.1 MPa is used as a breathing mixture. It is shown that these characteristics linearly depend on the partial nitrogen and oxygen pressure and hyperbaric bradycardia essentially decreases in the final period of isopression due to toxic oxygen effect. Cytochrome C decreases hyperbaric bradycardia. Under hyperbaric conditions the regulation of cardiac rhythm proceeds with altered central vegetative effects provided a direct effect of higher nitrogen and oxygen pressure on the sinusal node cells.     

Oxidative stress is fundamental to hyperbaric oxygen therapy

The goal of this review is to outline advances addressing the role that reactive species of oxygen and nitrogen play in therapeutic mechanisms of hyperbaric oxygen. The review will be organized around major categories of problems or processes where controlled clinical trials have demonstrated clinical efficacy for hyperbaric oxygen therapy. Reactive species are now recognized to play a major role in cell signal transduction cascades, and the discussion will focus on how hyperbaric oxygen acts through these pathways to mediate wound healing and ameliorate postischemic and inflammatory injuries.     

BCNU-induced protection from hyperbaric hyperoxia: role of glutathione metabolism

To explore the role of the glutathione oxidation-reduction cycle in altering the sensitivity of rats to the effects of hyperbaric hyperoxia, we administered N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) to decrease tissue glutathione reductase activity. We then exposed these animals and their matched vehicle-treated controls to 100% O2 at 4 ATA. Animals that received BCNU and were immediately exposed to hyperbaric O2 showed enhanced toxicity by seizing earlier in the exposure than controls. Animals that received BCNU 18 h before the hyperbaric O2 exposure were paradoxically protected from the effects of the exposure with a prolongation of their time to initial seizure and a marked increase in their survival time during the exposure. Tissue glutathione concentrations were also measured in the various groups and the hyperbaric O2 exposure produced marked decreases in hepatic glutathione levels in all control animals. In animals treated with BCNU 18 h before exposure, hepatic glutathione concentrations also decreased, but the concentrations had significantly increased during the 18-h waiting period, allowing these animals to maintain hepatic levels in the normal range even during their hyperbaric exposures. We conclude that treatment of rats with BCNU 18 h before exposure to hyperbaric hyperoxia results in enhanced protection of the animals during the exposure.