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SCUBA diving poses risks due to pressure changes during descent (compression) and ascent (decompression). Decompression sickness (DCS) occurs due to gas bubble formation as the pressure decreases, causing joint pain, numbness, dizziness, or even paralysis and death. Immediate treatment involves 100% oxygen to help eliminate inert gases and hyperbaric oxygen therapy (HBOT), which is essential to reduce gas emboli formation and inflammation, thus improving symptoms. We evaluated oxy-inflammation biomarkers in the saliva and urine of nine subjects pre- and post-technical dive on the Haven wreck (GE, Italy). A case of DCS occurred during the dive. The injured diver was treated immediately with O 2 and transported to the hyperbaric center of "ASST Ospedale Ca Granda" in Milan. He was treated following the U.S. Navy Treatment Table 5 at 2.8 ATA and the day after with Table 15 at 2.4 ATA. Venous blood and urine samples were collected before and after each HBO treatment. Our study shows that dive increased oxy-inflammation biomarkers (ROS +126%; lipid peroxidation +23%; interleukins-6 +81%, -1β +19%, and TNFα +84%) and nitric oxide metabolites levels (+36%). HBOT after a DCS episode reduced oxidative stress, lowering the very high marker of lipid peroxidation (8-iso-PGF2α), and inhibited inflammatory interleukins. Overall, HBOT improved physiological responses in the diver affected by DCS.

Decompression sickness (DCS) is a systemic syndrome that can occur after an environmental pressure reduction. Previously, we showed that the plasmatic tetrameric form of transthyretin (TTR) nearly disappeared in rats suffering DCS but not in asymptomatic ones. In this pilot study, we assessed whether the resistance to DCS could be associated with polymorphism of the gene of TTR. For this study, Sanger sequencing was performed on purified PCR products from the liver of 14-week-old male and female standard and DCS-resistant rats (n = 5 per group). Hepatic TTR mRNA expression was assessed by RT-qPCR in 18-19 week-old male and female standard and resistant rats (n = 6 per group). There is a synonymous single nucleotide polymorphism (SNP) on the third base of codon 46 (c.138 C > T). The thymine allele was present in 90% and 100% of males and females standard, respectively. However, this allele is present in only 30% of DCS-resistant males and females (p = 0.0002301). In the liver, there is a significant effect of the resistance to DCS (p = 0.043) and sex (p = 0.047) on TTR expression. Levels of TTR mRNA were lower in DCS-resistant animals. To conclude, DCS resistance might be associated with a SNP and a lower expression of TTR., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

We hypothesized that early intra-central nervous system (CNS) responses in a murine model of decompression sickness (DCS) would be reflected by changes in the microparticles (MPs) that exit the brain via the glymphatic system, and due to systemic responses the MPs would cause inflammatory changes lasting for many days leading to functional neurological deficits. Elevations on the order of threefold of blood-borne inflammatory MPs, neutrophil activation, glymphatic flow, and neuroinflammation in cerebral cortex and hippocampus were found in mice at 12 days after exposure to 760 kPa of air for 2 h. Mice also exhibited a significant decline in memory and locomotor activity, as assessed by novel object recognition and rotarod testing. Similar inflammatory changes in blood, neuroinflammation, and functional impairments were initiated in naïve mice by injection of filamentous (F-) actin-positive MPs, but not F-actin-negative MPs, obtained from decompressed mice. We conclude that high pressure/decompression stress establishes a systemic inflammatory process that results in prolonged neuroinflammation and functional impairments in the mouse decompression model. NEW & NOTEWORTHY Elevated glymphatic flow due to astrocyte and microglial activation from high-pressure exposure triggers release of microparticles (MPs) to the circulation where neutrophil activation and production of filamentous (F)-actin expressing MPs result in a persistent feed-forward neuroinflammatory cycle and functional deficits lasting for at least 12 days.

In some complicated situations, decompression sickness (DCS) combined with other injuries, such as irradiation, will seriously endanger life safety. However, it is still unclear whether irradiation will increase the incidence of DCS. This study was designed to investigate the damage effects of irradiation on decompression injury and the underlying mechanism. Sprague-Dawley rats were exposed to irradiation followed by hyperbaric decompressing and the mortality and decompression symptoms were observed. Lung tissue and bronchoalveolar lavage fluid were collected to detect the lung lesion, inflammation response, activity of the angiotensin system, oxidative stress, and relative signal pathway by multiple methods, including Q-PCR, western blot, and ELISA. As a result, pre-exposure to radiation significantly exacerbated disease outcomes and lung lesions of DCS. Mechanically, the up-regulation of angiotensin-converting enzyme expression and angiotensin II levels was responsible for the exacerbated DCS and lung lesions caused by predisposing irradiation exposure. Oxidative stress and PI3K/AKT signal pathway activation in pulmonary tissue were enhanced after irradiation plus decompression treatment. In conclusion, our results suggested that irradiation could exacerbate lung injury and the outcomes of DCS by activating the angiotensin system, which included eliciting oxidative stress and activation of the PI3K/AKT signal pathway., (© 2023. The Author(s).)

Blood-borne extracellular vesicles and inflammatory mediators were evaluated in divers using a closed circuit rebreathing apparatus and custom-mixed gases to diminish some diving risks. "Deep" divers ( n = 8) dove once to mean (±SD) 102.5 ± 1.2 m of sea water (msw) for 167.3 ± 11.5 min. "Shallow" divers ( n = 6) dove 3 times on day 1, and then repetitively over 7 days to 16.4 ± 3.7 msw, for 49.9 ± 11.9 min. There were statistically significant elevations of microparticles (MPs) in deep divers (day 1) and shallow divers at day 7 that expressed proteins specific to microglia, neutrophils, platelets, and endothelial cells, as well as thrombospondin (TSP)-1 and filamentous (F-) actin. Intra-MP IL-1β increased by 7.5-fold ( p < 0.001) after day 1 and 41-fold ( p = 0.003) at day 7. Intra-MP nitric oxide synthase-2 (NOS2) increased 17-fold ( p < 0.001) after day 1 and 19-fold ( p = 0.002) at day 7. Plasma gelsolin (pGSN) levels decreased by 73% ( p < 0.001) in deep divers (day 1) and 37% in shallow divers by day 7. Plasma samples containing exosomes and other lipophilic particles increased from 186% to 490% among the divers but contained no IL-1β or NOS2. We conclude that diving triggers inflammatory events, even when controlling for hyperoxia, and many are not proportional to the depth of diving.

This project investigated glial-based lymphatic (glymphatic) function and its role in a murine model of decompression sickness (DCS). DCS pathophysiology is traditionally viewed as being related to gas bubble formation from insoluble gas on decompression. However, a body of work implicates a role for a subset of inflammatory extracellular vesicles, 0.1 to 1 µm microparticles (MPs) that are elevated in human and rodent models in response to high gas pressure and rise further after decompression. Herein, we describe immunohistochemical and Western blot evidence showing that following high air pressure exposure, there are elevations of astrocyte NF-κB and microglial-ionized calcium-binding adaptor protein-1 (IBA-1) along with fluorescence contrast and MRI findings of an increase in glymphatic flow. Concomitant elevations of central nervous system-derived MPs coexpressing thrombospondin-1 (TSP) drain to deep cervical nodes and then to blood where they cause neutrophil activation. A new set of blood-borne MPs are generated that express filamentous actin at the surface that exacerbate neutrophil activation. Blood-brain barrier integrity is disrupted due to activated neutrophil sequestration that causes further astrocyte and microglial perturbation. When postdecompression node or blood MPs are injected into naïve mice, the same spectrum of abnormalities occur and they are blocked with coadministration of antibody to TSP. We conclude that high pressure/decompression causes neuroinflammation with an increased glymphatic flow. The resulting systemic liberation of TSP-expressing MPs sustains the neuroinflammatory cycle lasting for days. NEW & NOTEWORTHY A murine model of central nervous system (CNS) decompression sickness demonstrates that high gas pressure activates astrocytes and microglia triggering inflammatory microparticle (MP) production. Thrombospondin-expressing MPs are released from the CNS via enhanced glymphatic flow to the systemic circulation where they activate neutrophils. Secondary production of neutrophil-derived MPs causes further cell activation and neutrophil adherence to the brain microvasculature establishing a feed-forward neuroinflammatory cycle.

On one side, decompression sickness (DCS) with neurological disorders lead to a reshuffle of the fecal metabolome from rat caecum. On the other side, there is high inter-individual variability in terms of occurrence of DCS. One could wonder whether the fecal metabolome could be linked to the DCS-susceptibility. We decided to study male and female rats selected for their resistance to decompression sickness, and we hypothesize a strong impregnation concerning the fecal metabolome. The aim is to verify whether the rats resistant to the accident have a fecal metabolomic signature different from the stem generations sensitive to DCS. 39 DCS-resistant animals (21 females and 18 males), aged 14 weeks, were compared to 18 age-matched standard Wistar rats (10 females and 8 males), i.e., the same as those we used for the founding stock. Conventional and ChemRICH approaches helped the metabolomic interpretation of the 226 chemical compounds analyzed in the cecal content. Statistical analysis shows a panel of 81 compounds whose expression had changed following the selection of rats based on their resistance to DCS. 63 compounds are sex related. 39 are in common. This study shows the spectral fingerprint of the fecal metabolome from the caecum of a strain of rats resistant to decompression sickness. This study also confirms a difference linked to sex in the metabolome of non-selected rats, which disappear with selective breeding. Results suggest hormonal and energetic reshuffle, including steroids sugars or antibiotic compounds, whether in the host or in the microbial community.

Objective: Decompression sickness (DCS) causes serious brain hypoxic-ischemic injury. This experiment was designed to observe whether hyperbaric oxygen (HBO2) pretreatment played a neuroprotective effect in decompression sickness rat models and to explore the mechanism of protective effects., Methods: Sprague-Dawley (SD) male rats were pretreated with HBO2 and then underwent decompression to establish the DCS rat model. Antioxidant capacities were evaluated by detecting peroxides (GPx), superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in brains. The levels of metal elements manganese (Mn), zinc (Zn), iron (Fe) and magnesium (Mg) in brain tissues were assessed by flame atomic absorption spectrometry. Necrosis and apoptosis of neurons were assessed by H-E staining and immunohistochemical staining., Results: HBO2 pretreatment reduced the degree of necrosis and apoptosis in brain tissues of decompression sickness rat models. In addition, HBO2 pretreatment increased GPx, SOD and CAT activities and reduced MDA accumulation. It also increased the content of Mn, Zn, Fe and Mg in brain tissue, which are all related to free radical metabolism., Conclusion: These results suggested that HBO2 pretreatment has protective effects on brain injury of rats with decompression sickness. The mechanism of the protective effects may be related to reducing oxidative damage by affecting metal elements in vivo., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Massive bubble formation after diving can lead to decompression sickness (DCS), which can result in neurological disorders. We demonstrated that hydrogen production from intestinal fermentation could exacerbate DCS in rats fed with a standard diet. The aim of this study is to identify a fecal metabolomic signature that may result from the effects of a provocative hyperbaric exposure. The fecal metabolome was studied in two groups of rats previously fed with maize or soy in order to account for diet effects. 64 animals, weighing 379.0&#95;20.2 g on the day of the dive, were exposed to the hyperbaric protocol. The rats were separated into two groups: 32 fed with maize (Div MAIZE) and 32 fed with soy (Div SOY). Gut fermentation before the dive was estimated by measuring exhaled hydrogen. Following hyperbaric exposure, we assessed for signs of DCS. Blood was analyzed to assay inflammatory cytokines. Conventional and ChemRICH approaches helped the metabolomic interpretation of the cecal content. The effect of the diet is very marked at the metabolomic level, a little less in the blood tests, without this appearing strictly in the clinic status. Nevertheless, 37 of the 184 metabolites analyzed are linked to clinical status. 35 over-expressed compounds let suggest less intestinal absorption, possibly accompanied by an alteration of the gut microbial community, in DCS. The decrease in another metabolite suggests hepatic impairment. This spectral difference of the ceca metabolomes deserves to be studied in order to check if it corresponds to functional microbial particularities.

Endothelial dysfunction induced by bubbles plays an important role in decompression sickness (DCS), but the mechanism of which has not been clear. The present study was to investigate the role of autophagy in bubble-induced endothelial injury. Human umbilical vein endothelial cells (HUVECs) were treated with bubbles, autophagy markers and endothelial injury indices were determined, and relationship strengths were quantified. Effects of autophagy inhibitor 3-methyladenine (3-MA) were observed. Bubble contact for 1, 5, 10, 20 or 30 minutes induced significant autophagy with increases in LC3-II/I ratio and Beclin-1, and a decrease in P62, which correlated with bubble contact duration. Apoptosis rate, cytochrome C and cleaved caspase-3 increased, and cell viability decreased following bubble contact for 10, 20 or 30 minutes, but not for 1 or 5 minutes. Injuries in HUVECs were correlated with LC3-II/I ratio and partially reversed by 3-MA in 10, 20 or 30 minutes contact, but worsened in 1 or 5 minutes. Bubble pre-conditioning for 1 minutes resulted in increased cell viability and decreased apoptosis rate compared with no pre-conditioning, and 30-minutes pre-conditioning induced opposing changes, all of which were inhibited by 3-MA. In conclusion, autophagy was involved and played a biphasic role in bubble-induced endothelial injury., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Decompression illness (DCI) is a complex clinical syndrome caused by supersaturation of respiratory gases in blood and tissues after abrupt reduction in ambient pressure. The resulting formation of gas bubbles combined with pulmonary barotrauma leads to venous and arterial gas embolism. Severity of DCI depends on the degree of direct tissue damage caused by growing bubbles or indirect cell injury by impaired oxygen transport, coagulopathy, endothelial dysfunction, and subsequent inflammatory processes. The standard therapy of DCI requires expensive and not ubiquitously accessible hyperbaric chambers, so there is an ongoing search for alternatives. In theory, perfluorocarbons (PFC) are ideal non-recompressive therapeutics, characterized by high solubility of gases. A dual mechanism allows capturing of excess nitrogen and delivery of additional oxygen. Since the 1980s, numerous animal studies have proven significant benefits concerning survival and reduction in DCI symptoms by intravenous application of emulsion-based PFC preparations. However, limited shelf-life, extended organ retention and severe side effects have prevented approval for human usage by regulatory authorities. These negative characteristics are mainly due to emulsifiers, which provide compatibility of PFC to the aqueous medium blood. The encapsulation of PFC with amphiphilic biopolymers, such as albumin, offers a new option to achieve the required biocompatibility avoiding toxic emulsifiers. Recent studies with PFC nanocapsules, which can also be used as artificial oxygen carriers, show promising results. This review summarizes the current state of research concerning DCI pathology and the therapeutic use of PFC including the new generation of non-emulsified formulations based on nanocapsules.

In the context of decompression sickness, this paper presents analytical formulae and explanations for growth of a gas bubble in blood and other tissues in an unsteady diffusion field with a source or a sink. The formulae are valid for variable (through decompression) and constant (concerning diving stops/at sea level) ambient pressure. Under a linear decompression regime for ambient pressure, the gas bubble growth is proportional to ascent rate, tissue diffusivity and initial tissue tension and inversely proportional to surface tension, initial ambient pressure and the strength of the source/sink parameter [Formula: see text] which gives the conditions for bubble growth. We find that the growth process is noticeably affected by changing k-values within a specified range, with no significant effect on the value of the bubble radius when k is outside this range. We discuss the effect of the presence of multiple bubbles, and of repetitive diving. Of the three available models for bubble growth, the predicted time to completion is longest in the model by Srinivasan et al. (J Appl Physiol 86:732-741, 1999), where the bubble grows in a steady diffusion field, but shortest in the model we describe for k-values closest to the boundaries of the interval [Formula: see text]. This is because our model considers the effect of the presence of a source, increasing the bubble growth rate and not taken into account in our previous (2010) model predicting an intermediate timeframe for bubble growth. We believe our new model provides a more accurate and widely applicable description of bubble growth in decompression sickness than previous versions.

Hyperbaric oxygen (HBO 2 ) became a mainstay for treating decompression sickness (DCS) because bubbles are associated with the disorder. Inflammatory processes including production of circulating microparticles (MPs) have now been shown to occur with DCS, leading to questions regarding pathophysiology and the role for HBO 2 . We investigated effects of HBO 2 on mice exposed to 790 kPa air pressure for 2 h, which triggers elevations of MPs ladened with interleukin (IL)-1β that cause diffuse vascular injuries. Exposure to 283 kPa O 2 (HBO 2 ) inhibited MP elevations at 2 h postdecompression by 50% when applied either prophylactically or as treatment after decompression, and the MP number remained suppressed for 13 h in the prophylactic group. Particle content of IL-1β at 2 h postdecompression was 139.3 ± 16.2 [means ± SE; n = 11, P < 0.05) pg/million MPs vs. 8.2 ± 1.0 ( n = 15) in control mice, whereas it was 31.5 ± 6.1 ( n = 6, not significant vs. control (NS)] in mice exposed to HBO 2 prophylactically, and 16.6 ± 6.3 ( n = 7, NS) when HBO 2 was administered postdecompression. IL-1β content in MPs was similar in HBO 2 -exposed mice at 13 h postdecompression. HBO 2 also inhibited decompression-associated neutrophil activation and diffuse vascular leak. Immunoprecipitation studies demonstrated that HBO 2 inhibits high-pressure-mediated neutrophil nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 inflammasome oligomerization. Furthermore, MPs isolated from decompressed mice cause vascular injuries when injected into naïve mice, but if decompressed mice were exposed to HBO 2 before MP harvest, vascular injuries were inhibited. We conclude that HBO 2 impedes high-pressure/decompression-mediated inflammatory events by inhibiting inflammasome formation and IL-1β production. NEW & NOTEWORTHY High pressure/decompression causes vascular damage because it stimulates production of microparticles that contain high concentrations of interleukin-1β, and hyperbaric oxygen can prevent injuries.

Decompression sickness (DCS) occurs because of an excessively rapid and extensive reduction of the ambient pressure. Bubble-induced spinal cord ischemia is generally considered as a part of neurological DCS pathogenesis. Because helium preconditioning (HPC) recently demonstrated beneficial properties against ischemic damage, we hypothesized that HPC may decrease the neurological deficits of DCS in rats. Seventy-five male Sprague-Dawley rats were divided into a non-HPC group ( n = 25) and a HPC group ( n = 25) and 25 naive animals that were euthanized for histological examination ( n = 5) or anesthetized for baseline somatosensory evoked potential (SSEP) recordings ( n = 20). To induce DCS, rats were compressed with air to a pressure of 709 kPa for 60 min and decompressed at a rate of 203 kPa/min. HPC was administered as three episodes of 79% helium-21% oxygen mixture inhalation for 5 min interspersed with 5 min of air breathing. We found that HPC resulted in significantly decreased DCS incidence and delay of DCS onset. HPC also improved animal performance on the grip test after decompression and significantly ameliorated decompression-induced decrease of platelet number. Furthermore, the incidence of abnormal SSEP waves and histological spinal lesions was significantly reduced by HPC. We conclude that HPC can decrease the occurrence of DCS and ameliorate decompression-induced neurological deficits. NEW & NOTEWORTHY Helium preconditioning ameliorates decompression-induced neurological deficits in rats. Helium breathing before air dives may prevent neurological deficit and attenuate symptoms after decompression.

Introduction: High concentration normobaric oxygen (O₂) is a priority in treating divers with suspected decompression illness. The effect of different O₂ mask configurations on tissue oxygenation when breathing with a demand valve was evaluated., Methods: Sixteen divers had tissue oxygen partial pressure (PtcO₂) measured at six limb sites. Participants breathed O₂ from a demand valve using: an intraoral mask (IOM®) with and without a nose clip (NC), a pocket face mask and an oronasal mask. In-line inspired O₂ (FIO₂) and nasopharyngeal FIO₂ were measured. Participants provided subjective ratings of mask comfort, ease of breathing and holding in position., Results: PtcO₂ values and nasopharyngeal FIO₂ (median and range) were greatest using the IOM with NC and similar with the IOM without NC. O₂ measurements were lowest with the oronasal mask which also was rated as the most difficult to breathe from and to hold in position. The pocket face mask was reported as the most comfortable to wear. The NC was widely described as uncomfortable. The IOM and pocket face mask were rated best for ease of breathing. The IOM was rated as the easiest to hold in position., Conclusion: Of the commonly available O₂ masks for use with a demand valve, the IOM with NC achieved the highest PtcO₂ values. PtcO₂ and nasopharyngeal FIO₂ values were similar between the IOM with and without NC. Given the reported discomfort of the NC, the IOM without NC may be the best option., (Copyright: This article is the copyright of the authors who grant Diving and Hyperbaric Medicine a non-exclusive licence to publish the article in electronic and other forms.)

While barotrauma, decompression sickness, and drowning-related injuries are common morbidities associated with diving and decompression from depth, it remains unclear what impact rapid decompression has on mitochondrial function. In vitro diving simulation was performed with human dermal fibroblast cells subjected to control, air, nitrogen, and oxygen dive conditions. With the exception of the gas mixture, all other related variables, including absolute pressure exposure, dive and decompression rates, and temperature, were held constant. High-resolution respirometry was used to examine key respiratory states. Mitochondrial dynamic function, including net movement, number, and rates of fusion/fission events, was obtained from fluorescence microscopy imaging. Effects of the dive conditions on cell cytoskeleton were assessed by imaging both actin and microtubules. Maximum respiration was lower in fibroblasts in the air group than in the control and nitrogen groups. The oxygen group had overall lower respiration when compared with all other groups. All groups demonstrated lower mitochondrial motility when compared with the control group. Rates of fusion and fission events were the same between all groups. There were visible differences in cell morphology consistent with the actin staining; however, there were no appreciable changes to the microtubules. This is the first study to directly assess mitochondrial respiration and dynamics in a cell model of decompression. Both hyperbaric oxygen and air dive conditions produce deleterious effects on overall mitochondrial health in fibroblasts.

Systemic hypobaric hypoxia is reported to cause renal damage; nevertheless the exact pathophysiological mechanisms are not completely understood. Therefore, the present study aims to explore renal pathophysiology by using proteomics approach under hypobaric hypoxia. Six to eight week old male Sprague Dawley rats were exposed to hypobaric hypoxia equivalent to altitude of 7628 metres (pO2-282mmhg) at 28°C and 55% humidity in decompression chamber for different time intervals; 1, 3, and7 days. Various physiological, proteomic and bioinformatic studies were carried out to examine the effect of chronic hypobaric hypoxia on kidney. Our data demonstrated mild to moderate degenerative tubular changes, altered renal function, injury biomarkers and systolic blood pressure with increase in duration of hypobaric hypoxia exposure. Renal proteomic analysis showed 38 differential expressed spots, out of which 25 spots were down regulated and 13 were up regulated in 7 dayhypobarichypoxic exposure group of rats as compared to normoxia control. Identified proteins were involved in specific molecular changes pertinent to endogenous redox pathways, cellular integrity and energy metabolism. The study provides an empirical evidence of renal homeostasis under hypobaric hypoxia by investigating both physiological and proteomics changes. The identification of explicit key proteins provides a valuable clue about redox signalling mediated renal damage under hypobaric hypoxia., Competing Interests: The authors have declared that no competing interests exist.

Diving air-breathing vertebrates have long been considered protected against decompression sickness (DCS) through anatomical, physiological, and behavioural adaptations. However, an acute systemic gas and fat embolic syndrome similar to DCS in human divers was described in beaked whales that stranded in temporal and spatial association with military exercises involving high-powered sonar. More recently, DCS has been diagnosed in bycaught sea turtles. Both cases were linked to human activities. Two Risso's dolphin (Grampus griseus) out of 493 necropsied cetaceans stranded in the Canary Islands in a 16-year period (2000-2015), had a severe acute decompression sickness supported by pathological findings and gas analysis. Deadly systemic, inflammatory, infectious, or neoplastic diseases, ship collision, military sonar, fisheries interaction or other type of lethal inducing associated trauma were ruled out. Struggling with a squid during hunting is discussed as the most likely cause of DCS.

Background and Aims: Severe decompression sickness (DCS) is a multi-organ injury. This study investigated the preventive effects of rosiglitazone on liver injury following rapid decompression in mice and examined the underlying mechanisms., Methods: Mice were randomly divided into four groups: a control group, vehicle group, and rosiglitazone (5 and 10 mg·kg⁻¹) groups, the latter three being exposed to a pressure of 911 kPa. Haematoxylin and eosin staining, plasma levels of alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase and blood cell counts were used to evaluate liver injury at 30 min after rapid decompression. The expression of endothelial and inducible nitric oxide synthase (iNOS) and its phosphorylation were measured to uncover the underlying molecular mechanisms., Results: A significant increase in plasma ALT, red blood cells and platelets, and a decrease in neutrophils were observed in the vehicle group. Furthermore, the expression of iNOS, E-selectin and the total level of NO in hepatic tissue, and soluble E-selectin in the plasma were significantly elevated in the vehicle group. Rosiglitazone pre-treatment prevented the increases in ALT (and AST), soluble E-selectin concentration, red blood cells and platelet counts. Moreover, rosiglitazone reduced over-expression of iNOS and the NO level, prevented the fall in neutrophil count and promoted the phosphorylation of iNOS in the liver., Conclusions: Pre-treatment with rosiglitazone ameliorated liver injury from severe DCS. This preventive effect may be partly mediated by stimulating endothelial NO production, improving endothelial function and limiting inflammatory processes.

Decompression sickness (DCS) is the collective term for an array of signs and symptoms triggered by ambient pressure reduction. It is of particular concern to divers as they decompress on ascend from depth to sea surface, but despite a long history of studies the determinants of DCS risk are incompletely understood and there are no validated biomarkers. In this issue of Proteomics Clinical Applications, Lautridou et al. [8] report on their search for DCS biomarkers in rats exposed to simulated diving. By comparing the plasma proteomes from animals showing neurological symptoms to those emerging from dives unaffected, they identified several high-abundance proteins not previously associated with DCS. The most significant finding was a near depletion of thyroxine- and vitamin A transporter transthyretin in symptomatic rats. In addition to their potential role as diagnostic biomarkers, the proteins identified in Lautridou's study may offer new pieces in the yet incomplete puzzle of DCS etiology., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Studies conducted in divers indicate that endothelium function is impaired following a dive even without decompression sickness (DCS). Our previous experiment conducted on rat isolated vessels showed no differences in endothelium-dependent vasodilation after a simulated dive even in the presence of DCS, while contractile response to phenylephrine was progressively impaired with increased decompression stress. This study aimed to further investigate the effect of DCS on vascular smooth muscle. Thirty-two male Sprague-Dawley rats were submitted to the same hyperbaric protocol and classified according to the severity of DCS: no-DCS (without clinical symptoms), mild-DCS, or severe-DCS (dead within 1 h). A control group remained at atmospheric pressure. Isometric tension was measured in rings of abdominal aorta and mesenteric arteries. Single dose contraction was assessed with KCl solution. Dose-response curves were obtained with phenylephrine and endothelin-1. Phenylephrine-induced contraction was observed in the presence of antioxidant tempol. Additionally, plasma concentrations of angiotensin II, angiotensin-converting enzyme, and thiobarbituric acid reactive substances (TBARS) were assessed. Response to phenylephrine was impaired only among mild-DCS in both vessels. Dose-response curves to endothelin-1 were impaired after mild-DCS in mesenteric and severe-DCS in aorta. KCl-induced contraction was affected after hyperbaric exposure regardless of DCS status in aorta only. These results confirm postdive vascular dysfunction is dependent on the type of vessel. It further evidenced that vascular dysfunction is triggered by DCS rather than by diving itself and suggest the influence of circulating factor/s. Diving-induced impairment of the L-type voltage-dependent Ca(2+) channels and/or influence of renin-angiotensin system is proposed., (Copyright © 2016 the American Physiological Society.)

Despite state-of-the-art hyperbaric oxygen (HBO) treatment, about 30% of patients suffering neurologic decompression sickness (DCS) exhibit incomplete recovery. Since the mechanisms of neurologic DCS involve ischemic processes which result in excitotoxicity, it is likely that HBO in combination with an anti-excitotoxic treatment would improve the outcome in patients being treated for DCS. Therefore, in the present study, we investigated the effect of the noble gas xenon in an ex vivo model of neurologic DCS. Xenon has been shown to provide neuroprotection in multiple models of acute ischemic insults. Fast decompression compared to slow decompression induced an increase in lactate dehydrogenase (LDH), a well-known marker of sub-lethal cell injury. Post-decompression administration of xenon blocked the increase in LDH release induced by fast decompression. These data suggest that xenon could be an efficient additional treatment to HBO for the treatment of neurologic DCS.

Objective: To observe the pathological changes in rabbits with spinal cord injury induced by decompression sickness (DCS), and to investigate the role of tumor necrosis factor-alpha (TNF-α) in spinal cord injury induced by DCS., Methods: Rabbits were randomly divided into normal control group, DCS group, and safe decompression group. The rabbit model of DCS was established. Light microscopy, real-time PCR, and immunohistochemical method were used to observe the pathomorphological changes in the thoracolumbar spinal cord and the mRNA and protein expression of TNF-α, respectively. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to observe the apoptosis in the spinal cord., Results: In the DCS group, cavities formed in the white matter of spinal cord and gliosis occurred around necrotic areas. Moreover, the mRNA and protein expression of TNF-α was significantly higher in the DCS group than in the normal control group and the safe decompression group (P<0.01). The results of TUNEL showed that the number of positive apoptotic cells was significantly larger in the DCS group than in the normal control group and the safe decompression group (P<0.05)., Conclusion: Apoptosis plays an important role in spinal cord injury induced by DCS. In the early stage of DCS, the massive release of TNF-α initiates apoptosis and contributes to the pathological changes in spinal cord injury induced by DCS.

Decompression sickness (DCS) is a systemic disorder, assumed due to gas bubbles, but additional factors are likely to play a role. Circulating microparticles (MPs)--vesicular structures with diameters of 0.1-1.0 μm--have been implicated, but data in human divers have been lacking. We hypothesized that the number of blood-borne, Annexin V-positive MPs and neutrophil activation, assessed as surface MPO staining, would differ between self-contained underwater breathing-apparatus divers suffering from DCS vs. asymptomatic divers. Blood was analyzed from 280 divers who had been exposed to maximum depths from 7 to 105 meters; 185 were control/asymptomatic divers, and 90 were diagnosed with DCS. Elevations of MPs and neutrophil activation occurred in all divers but normalized within 24 h in those who were asymptomatic. MPs, bearing the following proteins: CD66b, CD41, CD31, CD142, CD235, and von Willebrand factor, were between 2.4- and 11.7-fold higher in blood from divers with DCS vs. asymptomatic divers, matched for time of sample acquisition, maximum diving depth, and breathing gas. Multiple logistic regression analysis documented significant associations (P < 0.001) between DCS and MPs and for neutrophil MPO staining. Effect estimates were not altered by gender, body mass index, use of nonsteroidal anti-inflammatory agents, or emergency oxygen treatment and were modestly influenced by divers' age, choice of breathing gas during diving, maximum diving depth, and whether repetitive diving had been performed. There were no significant associations between DCS and number of MPs without surface proteins listed above. We conclude that MP production and neutrophil activation exhibit strong associations with DCS., (Copyright © 2015 the American Physiological Society.)

Introduction: The Hypobaric Decompression Sickness (DCS) Treatment Model links a decrease in computed bubble volume from increased pressure (ΔP), increased oxygen (O2) partial pressure, and passage of time during treatment to the probability of symptom resolution [P(SR)]. The decrease in offending volume is realized in two stages: 1) during compression via Boyles law; and 2) during subsequent dissolution of the gas phase via the oxygen window., Methods: We established an empirical model for the P(SR) while accounting for multiple symptoms within subjects. The data consisted of 154 cases of hypobaric DCS symptoms with ancillary information from tests on 56 men and 18 women., Results: Our best estimated model is P(SR)=1/(1+exp(-(ln(ΔP)-1.510+0.795×AMB-0.00308×Ts)/0.478)), where ΔP is pressure difference (psid); AMB=1 if ambulation took place during part of the altitude exposure, otherwise AMB=0; and Ts is the elapsed time in minutes from the start of altitude exposure to recognition of a DCS symptom., Discussion: Values of ΔP as inputs to the model would be calculated from the Tissue Bubble Dynamics Model based on the effective treatment pressure: ΔP=P2-P1|=P1×V1/V2-P1, where V1 is the computed volume of a bubble at low pressure P1 and V2 is computed volume after a change to a higher pressure P2. If 100% ground-level oxygen was breathed in place of air, then V2 continues to decrease through time at P2 at a faster rate.

In underwater diving, decompression schedules are based on compartmental models of nitrogen and helium tissue kinetics. However, these models are not based on direct measurements of nitrogen and helium kinetics. In isoflurane-anesthetized sheep, nitrogen and helium kinetics in the hind limb (n = 5) and brain (n = 5) were determined during helium-oxygen breathing and after return to nitrogen-oxygen breathing. Nitrogen and helium concentrations in arterial, femoral vein, and sagittal sinus blood samples were determined using headspace gas chromatography, and venous blood flows were monitored continuously using ultrasonic Doppler. The experiment was repeated at different states of hind limb blood flow and cerebral blood flow. Using arterial blood gas concentrations and blood flows as input, parameters and model selection criteria of various compartmental models of hind limb and brain were estimated by fitting to the observed venous gas concentrations. In both the hind limb and brain, nitrogen and helium kinetics were best fit by models with multiexponential kinetics. In the brain, there were no differences in nitrogen and helium kinetics. Hind limb models fit separately to the two gases indicated that nitrogen kinetics were slightly faster than helium, but models with the same kinetics for both gases fit the data well. In the hind limb and brain, the blood:tissue exchange of nitrogen is similar to that of helium. On the basis of these results, it is inappropriate to assign substantially different time constants for nitrogen and helium in all compartments in decompression algorithms., (Copyright © 2015 the American Physiological Society.)

Decompression sickness (DCS) is a specific diving injury which sometimes may be life-threatening. Previous studies suggested that simvastatin (SIM) can protect against pathological inflammation and tissue damage. This study aimed to investigate whether SIM pretreatment could exert its beneficial effects on DCS. SIM was administered orally to adult male Sprague-Dawley rats for two weeks (2 mg/kg/day), then rats were subjected to a simulated dive at 700 kPa air pressure for 100 minutes before rapid decompression. After 30 minutes of symptom observation, lung tissue and blood samples were collected for further analysis. Compared to the vehicle-control, SIM pretreatment significantly decreased the incidence of DCS and ameliorated all parameters of pulmonary injuries, including lung dry/wet weight ratio, bronchoalveolar lavage fluid protein concentration, lung tissue malondialdehyde level and morphology. Moreover, SIM pretreatment abolished increases in systemic and pulmonary inflammation by reducing tumor necrosis factor-α levels in blood plasma and lung tissue. The results indicate that SIM may offer a novel pharmacological protection against injuries in DCS rats by inhibiting inflammatory responses. Further study is needed to understand the exact mechanisms.

Fast buoyancy ascent escape is the general submarine escape manner adopted by the majority of naval forces all over the world. However, if hyperbaric exposure time exceeds the time limit, fast buoyancy ascent escape has a high risk to result in decompression sickness (DCS). Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 have been all implicated in the process of inflammation associated with acute lung injury (ALI). Our work demonstrated that DCS caused by simulated fast buoyancy ascent escape could induce ALβ in the rat model. The purpose of the present work was to study the expression changes of TNF-α, IL-1β and IL-6 in the rat lung affected by DCS caused by simulated fast buoyancy ascent escape. The lung tissue mRNA levels of TNF-α, Il-1β and Il-6 were significantly increased at 0.5 hour after DCS caused by simulated fast buoyancy ascent escape. The lung contents of TNF-α, IL-1β and IL-6 were at an expression peak at 0.5 hour, although showing no statistical difference when compared with the normal control group. In conclusion, the rat lung expression variations of TNF-α, IL-1β and IL-6 are the most obvious at 0.5 hour within 24 hours after the lung injury by DCS caused by simulated fast buoyancy ascent escape.

Fast buoyancy ascent escape is one of the major naval submarine escape maneuvers. Decompression sickness (DCS) is the major bottleneck to increase the depth of fast buoyancy ascent escape. Rapid decompression induces the release of inflammatory mediators and results in tissue inflammation cascades and a protective anti-inflammatory response. In our previous study, we found that DCS caused by simulated fast buoyancy ascent escape could induce acute lung injury (ALI) and the expression changes of the proinflammatory cytokines: tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β and IL-6 in rat lung tissue. In order to study the expression change characteristics of TNF-α, IL-1β, IL-6, IL-10 and IL-13 in the rat lung of DCS caused by simulated fast buoyancy ascent escape, we detected the rat lung mRNA and protein levels of TNF-α, IL-1β, IL-6, IL-10 and IL-13 at 0.5 hour after DCS caused by simulated fast buoyancy ascent escape (fast escape group), compared with the normal control group (control group) and diving DCS (decompression group). We observed that DCS caused by simulated fast buoyancy ascent escape could increase the mRNA levels of TNF-α, IL-1β, IL-6, IL-10, and the protein levels of TNF-α, IL-10 in rat lung tissue. At the same time, we found that the protein level of IL-13 was also downregulated in rat lung tissue. TNF-α, IL-10 and IL-13 may be involved in the process of the rat lung injury of DCS caused by simulated fast buoyancy ascent escape. In conclusion, the expression changes of inflammatory factors in the rat lung of DCS caused by simulated fast buoyancy ascent escape were probably different from that in the rat lung of diving DCS, which indicated that the pathological mechanism of DCS caused by simulated fast buoyancy ascent escape might be different from that of diving DCS.

Objective: Symptoms consistent with neurological decompression sickness (DCS) in commercial breath-hold (Ama) divers has been reported from a few districts of Japan. The aim of this study was to detect circulating intravascular bubbles after repetitive breath-hold diving in a local area where DCS has been reported in Ama divers., Methods: The participants were 12 partially assisted (descent using weights) male Ama divers. The equipment (AQUALAB system) consisted of continuous-wave Doppler with a 5-MHz frequency, and the Doppler probe was placed in the precordial site with the ultrasonic wave directed into the pulmonary infundibulum. We carried out continuous monitoring for 10 minutes at the end of the series of repetitive dives, and the recordings were made on numerical tracks and graded in a blind manner by 2 experienced investigators, according to the Spencer Doppler code., Results: Depths and number of dives were 8 to 20 m and 75 to 131 times. Mean diving duration and surface interval were 64 ± 12 seconds and 48 ± 8 seconds, respectively (mean ± SD). We detected the lowest grade of intravascular bubbles (Spencer's grade I) in an Ama diver whose mean surface interval was only 35.2 ± 6.2 seconds. His mean descending, bottom, and ascending times were 10.4 ± 1.6 seconds, 39.2 ± 8 seconds, and 18.2 ± 3.0 seconds, respectively, over the course of 99 dives., Conclusions: Intravascular bubbles may be formed after repetitive breath-hold dives with short surface intervals or after a long breath-holding session in Ama divers. Symptoms consistent with neurological accidents in repetitive breath-hold diving may be caused in part by the intravascular presence of bubbles, indicating the need for safety procedures., (Copyright © 2014 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the changes in expression of tumor necrosis factor-alpha (TNF-α) and glial fibrillary acidic protein (GFAP) in rabbits with decompression disease (DCS), and to investigate the functioning mechanism., Methods: A total of 21 healthy adult rabbits were randomly divided into 3 groups: normal control group, DCS group, and safe relief group, with 7 rabbits in each group. A rabbit DCS model was established by quick decompression. The changes in pathological morphology and mRNA and protein expression of TNF-α and GFAP in the brain and spinal cord of rabbits with DCS were determined by light microscopy, real-time PCR, and immunohistochemistry, respectively., Results: Cavity formation was observed in the white matter of spinal cord in DCS group. The mRNA and protein expression of TNF-α and GFAP was significantly higher in the DCS group than in the normal control group and safe relief group (P < 0.01), while no significant differences were observed in the brain (P > 0.05)., Conclusion: Spinal cord is the main part of central nervous system injury in DCS. Activation of TNF-α and GFAP genes accompanied by increase in their protein expression can be observed at the early stage of DCS. The astrocytes and TNF-α play important roles in the process of spinal cord injury in DCS.

The concentration distribution around a growing nitrogen gas bubble in the blood and other bio tissues of divers who ascend to surface too quickly is obtained by Mohammadein and Mohamed model (2010) for variant and constant ambient pressure through the decompression process. In this paper, the growing of gas bubbles and concentration distribution under the effect of suction process are studied as a modification of Mohammadein and Mohamed model (zero suction). The growth of gas bubble is affected by ascent rate, tissue diffusivity, initial concentration difference, surface tension and void fraction. Mohammadein and Mohamed model (2010) is obtained as a special case from the present model. Results showed that, the suction process activates the systemic blood circulation and delay the growth of gas bubbles in the bio tissues to avoid the incidence of decompression sickness (DCS)., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Therapeutic mechanisms of action for hyperbaric oxygen (HBO2) therapy are based on elevation of both the partial pressure of inspired O2 and of the hydrostatic pressure. This last mechanism contributes to a compression of all gas-filled spaces in the body (Boyle's Law) and is relevant to treat conditions where gas bubbles are present in the body and cause the disease (e.g., intravascular embolism; decompression sickness with intravascular or intra-tissue bubbles). However, the majority of patients treated with HBO2 do not suffer from bubble-induced injuries, but derive clinical improvements from the elevated O2 partial pressures. High O2 partial pressures in various tissues increase the production of reactive O2 species (ROS) and also of reactive nitrogen species (RNS) because of hyperoxia. Most controlled studies have verified that the clinical efficacy from HBO2 derives from modulation of intracellular transduction cascades, leading to synthesis of growth factors and promoting wound healing and ameliorating post-ischemic and post-inflammatory injuries.

The study goal was to use membrane voltage changes during neurohypophysial action potential (AP) propagation as an index of nerve function to evaluate the role that circulating microparticles (MPs) play in causing central nervous system injury in response to decompression stress in a murine model. Mice studied 1 h following decompression from 790 kPa air pressure for 2 h exhibit a 45% broadening of the neurohypophysial AP. Broadening did not occur if mice were injected with the MP lytic agent polyethylene glycol telomere B immediately after decompression, were rendered thrombocytopenic, or were treated with an inhibitor of nitric oxide synthase-2 (iNOS) prior to decompression, or in knockout (KO) mice lacking myeloperoxidase or iNOS. If MPs were harvested from control (no decompression) mice and injected into naive mice, no AP broadening occurred, but AP broadening was observed with injections of equal numbers of MPs from either wild-type or iNOS KO mice subjected to decompression stress. Although not required for AP broadening, MPs from decompressed mice, but not control mice, exhibit NADPH oxidase activation. We conclude that inherent differences in MPs from decompressed mice, rather than elevated MPs numbers, mediate neurological injury and that a component of the perivascular response to MPs involves iNOS. Additional study is needed to determine the mechanism of AP broadening and also mechanisms for MP generation associated with exposure to elevated gas pressure.

Background: As is known, there are many cases when symptoms of decompression sickness (DCS) in divers appear extremely late (> 15 h after completion of diving) and there is much evidence for unsuccessful treatment of DCS by means of recompression. In this study, we have tried to gain insight into the roots of these phenomena., Methods: Using the mathematical model of extravascular gas bubble dynamics, we have analyzed the time history of such bubbles under typical air dives and recompression procedures used for DCS treatment., Results: If the parameters defining the bubble dynamics remained invariable, the bubbles formed in different body tissues would reach their maximal sizes within the well-known latency time range for DCS onset, and later these bubbles would dissolve completely during standard recompression procedures. Actually, the parameters defining the processes of bubble growth and dissolution vary with time., Conclusions: The symptoms of DCS that arise with abnormal latency may be induced by bubbles that grow a very long time in some tissues when the rate of nitrogen washout from them is reduced significantly due to vascular bubbles blocking the microcirculation. An abnormal latency of DCS onset may also appear when the negative effects of the initially asymptomatic bubbles are detected during the very slow process of their dissolution. The failure of recompression to resolve this DCS probably happens when the previously formed bubbles are large and located in tissues with less permeability so that they dissolve very slowly.

The study goal was to evaluate responses in humans following decompression from open-water SCUBA diving with the hypothesis that exertion underwater and use of a breathing mixture containing more oxygen and less nitrogen (enriched air nitrox) would alter annexin V-positive microparticle (MP) production and size changes and neutrophil activation, as well as their relationships to intravascular bubble formation. Twenty-four divers followed a uniform dive profile to 18 m of sea water breathing air or 22.5 m breathing 32% oxygen/68% nitrogen for 47 min, either swimming with moderately heavy exertion underwater or remaining stationary at depth. Blood was obtained pre- and at 15 and 120 min postdive. Intravascular bubbles were quantified by transthoracic echocardiography postdive at 20-min intervals for 2 h. There were no significant differences in maximum bubble scores among the dives. MP number increased 2.7-fold, on average, within 15 min after each dive; only the air-exertion dive resulted in a significant further increase to 5-fold over baseline at 2 h postdive. Neutrophil activation occurred after all dives. For the enriched air nitrox stationary at depth dive, but not for other conditions, the numbers of postdive annexin V-positive particles above 1 μm in diameter were correlated with intravascular bubble scores (correlation coefficients ∼0.9, P < 0.05). We conclude that postdecompression relationships among bubbles, MPs, platelet-neutrophil interactions, and neutrophil activation appear to exist, but more study is required to improve confidence in the associations.

Decompression sickness is initiated by gas bubbles formed during decompression, and it has been generally accepted that exercise before decompression causes increased bubble formation. There are indications that exercise-induced muscle injury seems to be involved. Trauma-induced skeletal muscle injury and vigorous exercise that could theoretically injure muscle tissues before decompression have each been shown to result in profuse bubble formation. Based on these findings, we hypothesized that exercise-induced skeletal muscle injury prior to decompression from diving would cause increase of vascular bubbles and lower survival rates after decompression. In this study, we examined muscle injury caused by eccentric exercise in rats prior to simulated diving and we observed the resulting bubble formation. Female Sprague-Dawley rats (n = 42) ran downhill (-16º) for 100 min on a treadmill followed by 90 min rest before a 50-min simulated saturation dive (709 kPa) in a pressure chamber. Muscle injury was evaluated by immunohistochemistry and qPCR, and vascular bubbles after diving were detected by ultrasonic imaging. The exercise protocol resulted in increased mRNA expression of markers of muscle injury; αB-crystallin, NF-κB, and TNF-α, and myofibrillar disruption with preserved sarcolemmal integrity. Despite evident myofibrillar disruption after eccentric exercise, no differences in bubble amounts or survival rates were observed in the exercised animals as compared to non-exercised animals after diving, a novel finding that may be applicable to humans.

Inert gases diffuse into tissues in proportion to ambient pressure, and when pressure is reduced, gas efflux forms bubbles due to the presence of gas cavitation nuclei that are predicted based on theory but have never been characterized. Decompression stress triggers elevations in number and diameter of circulating annexin V-coated microparticles (MPs) derived from vascular cells. Here we show that ∼10% MPs from wild-type (WT) but not inflammatory nitric oxide synthase-2 (iNOS) knockout (KO) mice increase in size when exposed to elevated air pressure ex vivo. This response is abrogated by a preceding exposure to hydrostatic pressure, demonstrating the presence of a preformed gas phase. These MPs have lower density than most particles, 10-fold enrichment in iNOS, and generate commensurately more reactive nitrogen species (RNS). Surprisingly, RNS only slowly diffuse from within MPs unless particles are subjected to osmotic stress or membrane cholesterol is removed. WT mice treated with iNOS inhibitor and KO mice exhibit less decompression-induced neutrophil activation and vascular leak. Contrary to injecting naïve mice with MPs from wild-type decompressed mice, injecting KO MPs triggers fewer proinflammatory events. We conclude that nitrogen dioxide is a nascent gas nucleation site synthesized in some MPs and is responsible for initiating postdecompression inflammatory injuries.

The mathematical model of gas bubble dynamics in body tissues was used for the analysis of evolution of their size during the treatment of decompression sickness in divers by means of recompression in accordance with RN table 72 and USN table 6A. It was shown that the duration of the process of bubble dissolution depends on the compression - decompression profile, as well on the initial size of a bubble, the oxygen content in the breathing mixture and the rate of nitrogen diffusion between a bubble and the surrounding tissue. The results of this study give the grounds to assume that the effect of recompression regimes used in the UK, USA and Russia promotes the treatment of DCS as a result of complete dissolution or significant reduction in the bubble sizes as well as due to therapeutic action of moderately hyperoxic breathing mixture on the tissues affected by bubbles.

For over a century, studies on body fat (BF) in decompression sickness and venous gas embolism of divers have been inconsistent. A major problem is that age, BF, and maximal oxygen consumption (Vo2max) show high multicollinearity. Using the Bühlmann model with eight parallel compartments, preceded by a blood compartment in series, nitrogen tensions and loads were calculated with a 40 min/3.1 bar (absolute) profile. Compared with Haldanian models, the new model showed a substantial delay in N2 uptake and (especially) release. One hour after surfacing, an increase of 14-28% in BF resulted in a whole body increase of the N2 load of 51%, but in only 15% in the blood compartment. This would result in an increase in the bubble grade of only 0.01 Kisman-Masurel (KM) units at the scale near KM = I-. This outcome was tested indirectly by a dry dive simulation (air breathing) with 53 male divers with a small range in age and Vo2max to suppress multicollinearity. BF was determined with the four-skinfold method. Precordial Doppler bubble grades determined at 40, 80, 120, and 160 min after surfacing were used to calculate the Kisman Integrated Severity Score and were also transformed to the logarithm of the number of bubbles/cm(2) (logB). The highest of the four scores yielded logB = -1.78, equivalent to KM = I-. All statistical outcomes of partial correlations with BF were nonsignificant. These results support the model outcomes. Although this and our previous study suggest that BF does not influence venous gas embolism (Schellart NAM, van Rees Vellinga TP, van Dijk FH, Sterk W. Aviat Space Environ Med 83: 951-957, 2012), more studies with different profiles under various conditions are needed to establish whether BF remains (together with age and Vo2max) a basic physical characteristic or will become less important for the medical examination and for risk assessment.

In order to develop more sensitive imaging tools for clinical use and basic research of spinal decompression sickness (DCS), we used diffusion tensor MRI (DTI) validated by histology to assess DCS-related tissue injury in sheep spinal cords. DTI is based on the measurement of water diffusion indices, including fractional anisotropy (FA) and mean diffusion (MD) to detect tissue microstructural abnormalities. In this study, we measured FA and MD in white and gray matter spinal cord regions in samples taken from sheep following hyperbaric exposure to 60-132 fsw and 0-180 minutes of oxygen pre-breathing treatment before rapid decompression. The main finding of the study was that decompression from >60 fsw resulted in reduced FA that was associated with cell death and disrupted tissue microstructure in spinal cord white matter tracts. Additionally, animals exposed to prolonged oxygen pre-breathing prior to decompression demonstrated reduced MD in spinal cord gray matter regions regardless of dive depth. To our knowledge, this is the first study to demonstrate the utility of DTI for the investigation of DCS-related injury and to define DTI biomarkers of spinal DCS.

Objective: To investigate the change of adhesion molecules in the lungs of rats suffered with decompression sickness (DCS)., Methods: Male SD rats were placed in the hyperbaric chamber, the chamber was compressed within 3 minutes to depths of 7 absolute atmosphere (ATA) and held at the designated depth for 60 min, then rapidly decompressed (3 min) to the surface. Rats were observed for signs of DCS after decompression. The brains, hepatis, and lungs were removed at 30 min, 6 h, 24 h post decompression, fixed and stained with hematoxylin eosin for routine histologic analysis. Lung paraffin sections were immunostained for the expression of intercellular adhesion molecule-1 (ICAM-1), E-selectin and major histocompatibility complex class II molecule (MHC-II). 2% evans blue dye in normal saline was injected 30 minutes prior to 6 h, 24 h before decompression. After 30 min, animals were perfused with 0.9% normal saline and lungs were harvested. Evans blue in the plasma was quantified by wavelength spectrophotometric analysis at 620 nm., Results: Results showed that there were hemorrhage and edema changes in the lungs, liver and brain at 30 min post decompression. Compared with control animals maintained at 1 ATA, the levels of E-selectin, ICAM-1 and MHC-II in the lungs of DCS rats were significantly increased post decompression. Compared with control animals, evans blue in the plasma was much higher at 6 h, 24 h post decompression., Conclusion: The bubble-induced adhesion molecule-mediated endothelial activation may be involved in the pathogenesis of DCS.

Preventive measures to reduce the risk of decompression sickness can involve several procedures such as oxygen breathing during in-water decompression. Theoretical predictions also suggest that brief periods of recompression during the course of decompression could be a method for controlling bubble formation. The aim of this study was to get clearer information about the effects of different experimental ascent profiles (EAPs) on bubble reduction, using pure oxygen or recompression during decompression for nitrox diving. Four EAPs were evaluated using bubble monitoring in a group of six military divers using Nitrox 40% O(2) breathing with a rebreather. For EAP 1 and 2, 100% O(2) was used for the end stage of decompression, with a 30% reduction of decompression time in EAP 1 and 50% in EAP 2, compared to the French navy standard schedule. For EAP 3 and 4, nitrox 40% O(2) was maintained throughout the decompression stage. EAP 3 is based on an air standard decompression schedule, whereas EAP 4 involved a brief period of recompression at the end of the stop. We found that EAP 1 significantly reduced bubble formation, whereas high bubble grades occurred with other EAPs. No statistical differences were observed in bubbles scores between EAP 3 and 4. One diver developed mild neurological symptoms after EAP 3. These results tend to demonstrate that the "oxygen window" plays a key role in the reduction of bubble production and that breathing pure oxygen during decompression stops is an optimal strategy to prevent decompression sickness for nitrox diving.

Bubbles in supersaturated tissues and blood occur in beaked whales stranded near sonar exercises, and post-mortem in dolphins bycaught at depth and then hauled to the surface. To evaluate live dolphins for bubbles, liver, kidneys, eyes and blubber-muscle interface of live-stranded and capture-release dolphins were scanned with B-mode ultrasound. Gas was identified in kidneys of 21 of 22 live-stranded dolphins and in the hepatic portal vasculature of 2 of 22. Nine then died or were euthanized and bubble presence corroborated by computer tomography and necropsy, 13 were released of which all but two did not re-strand. Bubbles were not detected in 20 live wild dolphins examined during health assessments in shallow water. Off-gassing of supersaturated blood and tissues was the most probable origin for the gas bubbles. In contrast to marine mammals repeatedly diving in the wild, stranded animals are unable to recompress by diving, and thus may retain bubbles. Since the majority of beached dolphins released did not re-strand it also suggests that minor bubble formation is tolerated and will not lead to clinically significant decompression sickness.

The goal of this study was to evaluate annexin V-positive microparticles (MPs) and neutrophil activation in humans following decompression from open-water SCUBA diving with the hypothesis that changes are related to intravascular bubble formation. Sixteen male volunteer divers followed a uniform profile of four daily SCUBA dives to 18 m of sea water for 47 min. Blood was obtained prior to and at 80 min following the first and fourth dives to evaluate the impact of repetitive diving, and intravascular bubbles were quantified by trans-thoracic echocardiography carried out at 20-min intervals for 2 h after each dive. MPs increased by 3.4-fold after each dive, neutrophil activation occurred as assessed by surface expression of myeloperoxidase and the CD18 component of β(2)-integrins, and there was an increased presence of the platelet-derived CD41 protein on the neutrophil surface indicating interactions with platelet membranes. Intravascular bubbles were detected in all divers. Surprisingly, significant inverse correlations were found among postdiving bubble scores and MPs, most consistently at 80 min or more after the dive on the fourth day. There were significant positive correlations between MPs and platelet-neutrophil interactions after the first dive and between platelet-neutrophil interactions and neutrophil activation documented as an elevation in β(2)-integrin expression after the fourth dive. We conclude that MPs- and neutrophil-related events in humans are consistent with findings in an animal decompression model. Whether there are causal relationships among bubbles, MPs, platelet-neutrophil interactions, and neutrophil activation remains obscure and requires additional study.

Background: Because it has earlier been shown that exercise 24 or two hours pre-dive may suppress the appearance of venous gas bubbles (VGB) in connection with the dive, we studied whether exercise before or during N2 elimination would influence the rate of the latter. Nitrogen elimination was recorded in eight volunteers breathing a normoxic O2+argon mixture for two hours. The N2 washout was preceded two (Condition A) or 24 hours (Condition B) earlier, by one hour of exercise at 85% VO2max (two hours of exercise interspersed with two hours of rest). In separate experiments, exercise at -40% of VO2max was performed throughout the two-hour washout (Condition C), and control experiments (Condition D) with denitrogenation without exercise were also performed., Results: There were no significant differences among conditions for the total N2 eliminated (904 +/- 196 mL). The half-times of N2 washout for A (35.2 +/- 10.8 minutes) and B (31.9 +/- 8.6 minutes) did not differ from control washouts. The rate of washout in C increased 14% compared to D (half-time: 30.4 +/- 7.6 vs. 34.5 +/- 7.8 minutes, p = 0.002), and correlated with cardiac output., Conclusion: Exercise 24 or two hours pre-N2 washout did not affect it, suggesting that the decreased VGB scores noted by others in dives preceded by conditions similar to A and B are not due to changes in nitrogen exchange but rather to factors related to bubble formation and/or appearance. That N2 elimination is enhanced by concomitant exercise makes physiological sense but does not necessarily explain the observation by others of a reduced risk of decompression sickness with exercise before diving.

Previous studies demonstrated that animals exposed to repeated compression-decompression stress acclimated (i.e., developed reduced susceptibility) to rapid decompression. This study endeavored to characterize inflammatory and stress-related gene expression and signal transduction associated with acclimation to rapid decompression. Rats were divided into four groups: 1) control-sham: pressure naïve rats; 2) acclimation-sham: nine acclimation dives [70 feet seawater (fsw), 30 min]; 3) control-dive: test dive only (175 fsw, 60 min); and 4) acclimation-dive: nine acclimation dives and a test dive. After the test dive, rats were observed for decompression sickness (DCS). Expression of 13 inflammatory and stress-related genes and Akt (or PKB, a serine/threonine protein kinase) and MAPK phosphorylation of lung tissue were examined. The expression of immediate early gene/transcription factor early growth response gene 1 (Egr-1) was observed in both control and acclimation animals with DCS but not in animals without DCS. Increased Egr-1 in control-dive animals with DCS was significantly greater than in acclimation-dive animals with DCS. TNF-α, IL-1β, IL-6, and IL-10 were significantly elevated in control-DCS animals. Acclimation-DCS animals had increased TNF-α, but there was no change in IL-1β, IL-6, and IL-10. High levels of Akt phosphorylation were observed in lungs of acclimation-sham, acclimation-dive, and control-dive animals; phosphorylated ERK1/2 was only observed in animals with DCS. This study suggests that activation of ERK1/2 and upregulation of Egr-1 and its target cytokine genes by rapid decompression may play a role in the initiation and progression of DCS. It may be that the downregulated expression of these genes in animals with DCS is associated with previous exposure to repeated compression-decompression cycles. This study represents an initial step toward understanding the molecular mechanisms associated with acclimation to decompression.

Deep tissue isobaric counterdiffusion that may cause unwanted bubble formation or transient bubble growth has been referred to in theoretical models and demonstrated by intravascular gas formation in animals, when changing inert breathing gas from nitrogen to helium after hyperbaric air breathing. We visually followed the in vivo resolution of extravascular air bubbles injected at 101 kPa into nitrogen supersaturated rat tissues: adipose, spinal white matter, skeletal muscle or tail tendon. Bubbles were observed during isobaric breathing-gas shifts from air to normoxic (80:20) heliox mixture while at 285 kPa or following immediate recompression to either 285 or 405 kPa, breathing 80:20 and 50:50 heliox mixtures. During the isobaric shifts, some bubbles in adipose tissue grew marginally for 10-30 min, subsequently they shrank and disappeared at a rate similar to or faster than during air breathing. No such bubble growth was observed in spinal white matter, skeletal muscle or tendon. In spinal white matter, an immediate breathing gas shift after the hyperbaric air exposure from air to both (80:20) and (50:50) heliox, coincident with recompression to either 285 or 405 kPa, caused consistent shrinkage of all air bubbles, until they disappeared from view. Deep tissue isobaric counterdiffusion may cause some air bubbles to grow transiently in adipose tissue. The effect is marginal and of no clinical consequence. Bubble disappearance rate is faster with heliox breathing mixtures as compared to air. We see no reason for reservations in the use of heliox breathing during treatment of air-diving-induced decompression sickness.

The analysis of probable causes for anomalously prolonged latent time of developing decompression sickness in divers after completion of air dives was carried out in the content of the theory of formation and subsequent evolution of gas bubbles in body tissues. This phenomenon gives grounds to consider that certain of the decompression bubbles have a prolonged lifetime and gradually increase their affect on adjacent tissues. The main causes of increasing the lifetime of these bubbles are the increase of their sires due to the reduction of tissue perfusion during decompression and the coalescence them to one another, as well the encrustation of bubbles by a layer of intercellular fluid elements that reduces the rate of nitrogen diffusion from bubbles to tissues and retards their dissolution. The bubble layer decreases also the gas pressure inside bubbles due to reduction of the surface tension action of intercellular fluid that results in additional reduction of the diffusion flow of nitrogen from bubbles and the rate of their dissolution. Moreover, taken alone, the process of bubble layer formation seems as one of the main mechanisms of tissue lesions by gas bubbles.

Diving and decompression performed under immersed conditions have been shown to reduce cardiac function. The mechanisms for these changes are not known. The effect of immersion before a simulated hyperbaric dive on cardiomyocyte function was studied. Twenty-three rats were assigned to four groups: control, 1 h thermoneutral immersion, dry dive, and 1 h thermoneutral immersion before a dive (preimmersion dive). Rats exposed to a dive were compressed to 700 kPa, maintained for 45 min breathing air, and decompressed linearly to the surface at a rate of 50 kPa/min. Postdive, the animals were anesthetized and the right ventricle insonated for bubble detection using ultrasound. Isolation of cardiomyocytes from the left ventricle was performed and studied using an inverted fluorescence microscope with video-based sarcomere spacing. Compared with a dry dive, preimmersion dive significantly increased bubble production and decreased the survival time (bubble grade 1 vs. 5, and survival time 60 vs. 17 min, respectively). Preimmersion dive lead to 18% decreased cardiomyocyte shortening, 20% slower diastolic relengthening, and 22% higher calcium amplitudes compared with controls. The protein levels of the sarco-endoplasmic reticulum calcium ATPase (SERCA2a), Na+/Ca2+ exchanger (NCX), and phospholamban phosphorylation in the left ventricular tissue were significantly reduced after both dry and preimmersion dive compared with control and immersed animals. The data suggest that immersion before a dive results in impaired cardiomyocyte and Ca2+ handling and may be a cellular explanation to reduced cardiac function observed in humans after a dive.