Microparticle-induced vascular injury in mice following decompression is inhibited by hyperbaric oxygen: effects on microparticles and interleukin-1β

Hyperbaric oxygen (HBO2) 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 HBO2. We investigated effects of HBO2 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 O2 (HBO2) 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 HBO2 prophylactically, and 16.6 ± 6.3 ( n = 7, NS) when HBO2 was administered postdecompression. IL-1β content in MPs was similar in HBO2-exposed mice at 13 h postdecompression. HBO2 also inhibited decompression-associated neutrophil activation and diffuse vascular leak. Immunoprecipitation studies demonstrated that HBO2 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 HBO2 before MP harvest, vascular injuries were inhibited. We conclude that HBO2 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.

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Provocative decompression causes diffuse vascular injury in mice mediated by microparticles containing interleukin-1β

Journal of Applied Physiology ◽

10.1152/japplphysiol.00620.2018 ◽

2018 ◽

Vol 125 (4) ◽

pp. 1339-1348 ◽

Cited By ~ 4

Author(s):

Stephen R. Thom ◽

Veena M. Bhopale ◽

Kevin Yu ◽

Ming Yang

Keyword(s):

High Pressure ◽

Cell Activation ◽

Decompression Sickness ◽

Ambient Pressure ◽

Activation Parameters ◽

Vascular Damage ◽

Interleukin 1Β ◽

Inflammasome Activation ◽

Activation Process ◽

Circulating Microparticles

Inflammatory mediators are known to be elevated in association with decompression from elevated ambient pressure, but their role in tissue damage or overt decompression sickness is unclear. Circulating microparticles (MPs) are also known to increase, and because interleukin (IL)-1β is packaged within these particles, we hypothesized that IL-1β was responsible for tissue injuries. Here, we demonstrate that elevations of circulating MPs containing up to ninefold higher concentrations of IL-1β occur while mice are exposed to high air pressure (790 kPa), whereas smaller particles carrying proteins specific to exosomes are not elevated. MPs number and intra-particle IL-1β concentration increase further over 13 h post decompression. MPs also exhibit intra-particle elevations of tumor necrosis factor-α, caspase-1, inhibitor of κB kinase-β, and inhibitor of κB kinase-γ, and elevated IL-6 is adsorbed to the surface of MPs. Contrary to lymphocytes, neutrophil nucleotide-binding oligomerization domain-like receptor, pyrin domain containing 3 (NLRP3) inflammasome oligomerization and cell activation parameters occur during high pressure exposure, and additional evidence for activation is manifested post decompression. Diffuse vascular damage, although not apparent immediately post decompression, was present 2 h later and remained elevated for at least 13 h. Prophylactic administration of an IL-1β receptor inhibitor or neutralizing antibody to IL-1β inhibited MPs elevations, increases of all MPs-associated pro-inflammatory agents, and vascular damage. We conclude that an auto-activation process triggered by high pressure stimulates MPs production and concurrent inflammasome activation, and IL-1β is a proximal factor responsible for further cytokine production and decompression-associated vascular injuries. NEW & NOTEWORTHY Elevations in circulating microparticles due to decompression have been documented in humans and animals. This report shows that intra-particle interleukin-1β causes vascular damage that can be abrogated by interventions directed against this cytokine.

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Plasma gelsolin modulates the production and fate of IL-1β-containing microparticles following high-pressure exposure and decompression

Journal of Applied Physiology ◽

10.1152/japplphysiol.01062.2020 ◽

2021 ◽

Author(s):

Veena M. Bhopale ◽

Deepa Ruhela ◽

Kaighley D. Brett ◽

Nathan Z. Nugent ◽

Noelle K. Fraser ◽

...

Keyword(s):

Skeletal Muscle ◽

High Pressure ◽

Decompression Sickness ◽

Human Neutrophils ◽

Capillary Leak ◽

Research Subjects ◽

Plasma Gelsolin ◽

Inflammatory Conditions ◽

Model Research ◽

Circulating Microparticles

Plasma gelsolin (pGSN) levels fall in association with diverse inflammatory conditions. We hypothesized pGSN would decrease due to the stresses imposed by high pressure and subsequent decompression, and repletion would ameliorate injuries in a murine decompression sickness (DCS) model. Research subjects were found to exhibit a modest decrease in pGSN level while at high pressure and a profound decrease after decompression. Changes occurred concurrent with elevations of circulating microparticles (MPs) carrying interleukin (IL)-1β. Mice exhibited a comparable decrease in pGSN after decompression along with elevations of MPs carrying IL-1β. Infusion of recombinant human (rhu)-pGSN into mice before or after pressure exposure abrogated these changes and prevented capillary leak in brain and skeletal muscle. Human and murine MPs generated under high pressure exhibited surface filamentous (F-) actin to which pGSN binds, leading to particle lysis. Additionally, human neutrophils exposed to high air pressure exhibit an increase in surface F-actin that is diminished by rhu-pGSN resulting in inhibition of MPs production. Administration of rhu-pGSN may have benefit as prophylaxis or treatment for DCS.

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Acclimatization to neurological decompression sickness in rabbits

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00260.2004 ◽

2004 ◽

Vol 287 (5) ◽

pp. R1214-R1218 ◽

Cited By ~ 16

Author(s):

Chien-Ling Su ◽

Chin-Pyng Wu ◽

Shao-Yuan Chen ◽

Bor-Hwang Kang ◽

Kun-Lun Huang ◽

...

Keyword(s):

High Pressure ◽

Stress Response ◽

Hyperbaric Oxygen ◽

Hyperbaric Oxygen Therapy ◽

Oxygen Therapy ◽

Decompression Sickness ◽

Control Group ◽

Neurological Score ◽

Pressure Cycle ◽

Subsequent Exposure

Diving acclimatization refers to a reduced susceptibility to acute decompression sickness (DCS) in individuals undergoing repeated compression-decompression cycles. We demonstrated in a previous study that the mechanism responsible for this acclimatization is similar to that of stress preconditioning. In this study, we investigated the protective effect of prior DCS preconditioning on the severity of neurological DCS in subsequent exposure to high pressure in rabbits. We exposed the rabbits ( n = 10) to a pressure cycle of 6 absolute atmospheres (ATA) for 90 min, which induced signs of neurological DCS in 60% of the animals. Twenty-four hours after the pressure cycle, rabbits with DCS expressed more heat-shock protein 70 (HSP70) in the lungs, liver, and heart than rabbits without signs of disease or those in the control group ( n = 6). In another group of rabbits ( n = 24), 50% of animals presented signs of neurological DCS after exposure to high pressure, with a neurological score of 46.5 (SD 19.5). A course of hyperbaric oxygen therapy alleviated the signs of neurological DCS and ensured the animals' survival for 24 h. Experiencing another pressure cycle of 6 ATA for 90 min, 50% of 12 rabbits with prior DCS preconditioning developed signs of DCS, with a neurological score of 16.3 (SD 28.3), significantly lower than that before hyperbaric oxygen therapy ( P = 0.002). In summary, our results show that the occurrence of DCS in rabbits after rapid decompression is associated with increased expression of a stress protein, indicating that the stress response is induced by DCS. This phenomenon was defined as “DCS preconditioning.” DCS preconditioning attenuated the severity of neurological DCS caused by subsequent exposure to high pressure. These results suggest that bubble formation in tissues activates the stress response and stress preconditioning attenuates tissue injury on subsequent DCS stress, which may be the mechanism responsible for diving acclimatization.

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Combined effect of denucleation and denitrogenation on the risk of decompression sickness in rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.91146.2008 ◽

2009 ◽

Vol 106 (4) ◽

pp. 1453-1458 ◽

Cited By ~ 16

Author(s):

R. Arieli ◽

E. Boaron ◽

A. Abramovich

Keyword(s):

High Pressure ◽

High Altitude ◽

Hyperbaric Oxygen ◽

Decompression Sickness ◽

Nitrogen Pressure ◽

Inert Gas ◽

Practical Application ◽

Air Exposure ◽

Nitrogen Washout ◽

Gas Micronuclei

We previously hypothesized that the number of bubbles emerging on decompression from a dive, and the resultant risk of decompression sickness (DCS), may be reduced by a process whereby effective gas micronuclei that might otherwise have formed bubbles on decompression are shrunk and eliminated. In a procedure defined by us as denucleation, exposure to hyperbaric oxygen (HBO) would result in oxygen replacing the resident gas in the micronuclei, to be subsequently consumed by the mitochondria when the oxygen pressure is reduced. Support for the validity of our hypothesis may be found in our previous studies on the transparent prawn and the reduction of DCS in the rat. In all of these studies, HBO pretreatment was given before supersaturation with inert gas at high pressure. The purpose of the present study was to compare DCS outcome in rats that underwent nitrogen washout (denitrogenation) alone (9 min O2 at 507 kPa) after exposure to air at high pressure (33 min at 1,266 kPa), and rats treated by both procedures (denitrogenation + denucleation; 8 min of O2 breathing followed by 5 min air breathing, both at 507 kPa) after high-pressure air exposure. This was done with the same nitrogen load in both groups before the final decompression (a nitrogen pressure of 467 kPa in fatty and 488 kPa in aqueous tissue). Six of 20 rats in the denitrogenation + denucleation group died, compared with 13 in the denitrogenation group ( P < 0.03). Three rats in the denitrogenation + denucleation group suffered mild DCS, recovering completely within 2 h of decompression. The present study indicates an advantage in considering both denitrogenation and denucleation before decompression. This may have practical application before escape from a disabled submarine, when aborting a technical dive, or in the preparation of aviators for high altitude.

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Successful treatment of decompression sickness complicated with acute hepatic infarction and acute kidney injury: a case report

Undersea and Hyperbaric Medicine ◽

10.22462/01.03.2019.10 ◽

2019 ◽

pp. 81-85

Author(s):

Se Hyun Oh ◽

◽

Hui Dong Kang ◽

Sang Ku Jung ◽

Sangchun Choi ◽

...

Keyword(s):

Acute Kidney Injury ◽

Case Report ◽

Hyperbaric Oxygen ◽

Successful Treatment ◽

Decompression Sickness ◽

Kidney Injury ◽

Pressure Change ◽

Hepatic Infarction ◽

Hbo2 Therapy

Decompression sickness is a disease caused by abrupt pressure change and presents various symptoms. To date, acute kidney injury associated with decompression sickness has been reported frequently, but there is no report of hepatic infarction associated with decompression sickness. We report a case of acute kidney injury and acute hepatic infarction treated with hyperbaric oxygen (HBO2) therapy and dialysis in a patient with severe decompression sickness after work diving.

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Functional MRI during hyperbaric oxygen: Effects of oxygen on neurovascular coupling and BOLD fMRI signals

NeuroImage ◽

10.1016/j.neuroimage.2015.06.082 ◽

2015 ◽

Vol 119 ◽

pp. 382-389 ◽

Cited By ~ 9

Author(s):

Damon P. Cardenas ◽

Eric R. Muir ◽

Shiliang Huang ◽

Angela Boley ◽

Daniel Lodge ◽

...

Keyword(s):

Functional Mri ◽

Hyperbaric Oxygen ◽

Neurovascular Coupling ◽

Bold Fmri ◽

Oxygen Effects

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Effects of hyperbaric oxygen therapy on NACHT domain-leucine-rich-repeat- and pyrin domain-containing protein 3 inflammasome expression in rats following spinal cord injury

Molecular Medicine Reports ◽

10.3892/mmr.2015.3314 ◽

2015 ◽

Vol 11 (6) ◽

pp. 4650-4656 ◽

Cited By ~ 10

Author(s):

FANG LIANG ◽

CHUNSHENG LI ◽

CHUNJIN GAO ◽

ZHUO LI ◽

JING YANG ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Hyperbaric Oxygen ◽

Hyperbaric Oxygen Therapy ◽

Oxygen Therapy ◽

Leucine Rich Repeat ◽

Pyrin Domain ◽

Cord Injury

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Spinal cord decompression sickness in an inside attendant after a standard hyperbaric oxygen treatment session

Diving and Hyperbaric Medicine Journal ◽

10.28920/dhm51.1.103-106 ◽

2021 ◽

Vol 51 (1) ◽

pp. 103-106

Author(s):

Jacek Kot ◽

◽

Ewa Lenkiewicz ◽

Edward Lizak ◽

Piotr Góralczyk ◽

...

Keyword(s):

Hyperbaric Oxygen ◽

Decompression Sickness ◽

Transoesophageal Echocardiography ◽

Medical Personnel ◽

Treatment Session ◽

Occupational Risk ◽

Additional Risk ◽

Hyperbaric Treatment ◽

Hyperbaric Exposure ◽

Spinal Cord Decompression

Medical personnel in hyperbaric treatment centres are at occupational risk for decompression sickness (DCS) while attending patients inside the multiplace hyperbaric chamber (MHC). A 51-year-old male hyperbaric physician, also an experienced diver, was working as an inside attendant during a standard hyperbaric oxygen therapy (HBOT) session (70 minutes at 253.3 kPa [2.5 atmospheres absolute, 15 metres’ seawater equivalent]) in a large walk-in MHC. Within 10 minutes after the end of the session, symptoms of spinal DCS occurred. Recompression started within 90 minutes with an infusion of lignocaine and hydration. All neurological symptoms resolved within 10 minutes breathing 100% oxygen at 283.6 kPa (2.8 atmospheres absolute) and a standard US Navy Treatment Table 6 was completed. He returned to regular hyperbaric work after four weeks of avoiding hyperbaric exposures. Transoesophageal echocardiography with a bubble study was performed 18 months after the event without any sign of a persistent (patent) foramen ovale. Any hyperbaric exposure, even within no-decompression limits, is an essential occupational risk for decompression sickness in internal hyperbaric attendants, especially considering the additional risk factors typical for medical personnel (age, dehydration, tiredness, non-optimal physical capabilities and frequent problems with the lower back).

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Effects of hyperbaric oxygen pretreatment on brain antioxidant capacity in rats with decompression sickness

Undersea and Hyperbaric Medicine ◽

10.22462/05.06.2021.9 ◽

2021 ◽

pp. 287-295

Author(s):

Ya Li ◽

◽

Xiaona Xu ◽

Junxiang Bao Bao ◽

Wenlan Wang ◽

...

Keyword(s):

Hyperbaric Oxygen ◽

Decompression Sickness ◽

Neuroprotective Effect ◽

Male Rats ◽

Protective Effects ◽

Sprague Dawley ◽

Rat Models ◽

Metal Elements ◽

Flame Atomic Absorption ◽

Brain Tissues

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.

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