Exposure to hyperbaric O2 levels leads to blood-brain barrier breakdown in rodents.

INTRODUCTION: Hyperbaric oxygen has been used as a medical treatment tool in hyperbaric chambers and is an integral part of professional and combat divers' activity. In extreme cases, exposure to hyperbaric oxygen can develop central nervous system oxygen toxicity (CNS-OT), which leads to seizures and eventually death. CNS-OT is caused by neuronal hyperactivity due to high oxygen levels, potentially damaging brain cells including the blood-brain barrier (BBB). However, the effect of hyperbaric oxygen levels on the healthy BBB has not been characterized directly yet. METHODS: Six or three different groups of ~ eight rats or mice, respectively, were exposed to increasing levels of partial pressure of oxygen (0.21 to 5 ATA) in a hyperbaric chamber, followed by MRI scanning with gadolinium. Statistical significance (adjusted p-value ≤ 0.05) was assessed using linear regression and ordinary one-way (rats) or two-way (mice) ANOVA with correction of multiple comparison tests. In rats, the effect of 100% oxygen at 5 ATA was independently validated using FITC-Dextran (5 kDa). Statistical significance (p-value ≤ 0.05) was assessed using Welch's t-test and effect size was calculated by Cohen's D. RESULTS: In rats, analyzed MRI scans showed a significant trend of increase in the % gadolinium in brain tissues as a result of hyperbaric oxygen pressures (p-value = 0.0079). The most significant increase was measured at 4 ATA compared to air (adjusted p-value = 0.0461). Significant increased FITC-Dextran levels were measured in the rats' brains under 100% oxygen at 5 ATA versus air (p-value = 0.0327; Effect size = 2.0). In mice, a significant increase in gadolinium penetration into the hippocampus and frontal cortex was measured over time (adjusted p-value < 0.05) under 100% oxygen at 3 and 5 ATA versus air, and between the treatments (adjusted p-value < 0.0001). CONCLUSIONS: The BBB is increasingly disrupted due to higher levels of hyperbaric oxygen in rodents, indicating a direct relation between hyperbaric oxygen and BBB dysregulation for the first time. We suggest considering this risk in different diving activities, and protocols using a hyperbaric chamber. On the other hand, this study highlights the potential therapeutic usage of hyperbaric oxygen for controlled drug delivery through the BBB into brain tissues in different brain-related diseases.

Symptoms of central nervous system oxygen toxicity during 100% oxygen breathing at normobaric pressure with increasing inspired levels of carbon dioxide: a case report.

The greatest danger faced by divers who use oxygen-enriched gas mixtures is central nervous system oxygen toxicity (CNS-OT). CNS-OT is characterised by convulsions resembling grand-mal epileptic seizures, which may terminate in drowning and death. Elevated arterial levels of carbon dioxide (CO2) (hypercapnia) represent a major risk factor for CNS-OT when breathing hyperoxic gas mixtures. To reduce the risk of a diver being involved in a CNS-OT incident due to hypercapnia, candidates for combat diving are examined at our institute using a routine physiological training procedure, in which they are tested for CO2 detection and retention. We present the case of a candidate for combat diving, who unexpectedly exhibited signs typical of CNS-OT while breathing pure oxygen under normobaric conditions with > 3 kPa inspired CO2. Severe headache and nausea, as well as facial muscle twitching, appeared during one of these routine tests. Subsequent medical examination including neurological tests, magnetic resonance imaging and an electroencephalogram were unremarkable. To the best of our knowledge, an event such as this has never previously been published in the medical literature. We present a discussion of the case, and a review of the relevant literature regarding CO2 as a risk factor for the development of CNS-OT.

Evaluating the thermal protection provided by a 2‒3 mm wet suit during fin diving in shallow water with a temperature of 16‒20°C.

INTRODUCTION: The purpose of the study was to evaluate the thermal protection provided by a 2-3 mm surfing wet suit during at least two hours of fin diving in shallow water with a temperature of 16-20°C. We examined the effect of wearing the suit while diving in cold water on cognitive performance, muscle strength, and hand motor function. METHODS: Subjects were six male well-trained rebreather divers, 19-23 years old, acclimatised to cold. They attended the laboratory on three separate occasions, when we conducted the experiment at one of three temperatures, 16, 18, and 20°C. Core temperature (gastrointestinal system), skin temperature, oxygen consumption, and cold perception were evaluated during the test. Before and immediately after the dives, subjects performed a series of cognitive, manual dexterity, and muscle strength tests. RESULTS: Core temperature decreased by 0.35-0.81°C over the two hours at all three water temperatures. No subject reached a core temperature below 35°C. The decrease in upper body skin temperature during the two hour dive ranged between 5.97 and 8.41°C (P < 0.05). Two hours diving in 16-20°C water resulted in a significant increase in the time taken to perform the task of unlinking and reassembling four shackles (∼30% longer, P < 0.05). No effect was found on the cognitive or muscle strength tests. CONCLUSIONS: A 2-3 mm wet suit provides adequate thermal protection in trained and cold-acclimatised young males engaged in active diving in shallow water with a temperature of 16°C and above.

The transition from day-to-night activity is a risk factor for the development of CNS oxygen toxicity in the diurnal fat sand rat (Psammomys obesus).

Performance and safety are impaired in employees engaged in shift work. Combat divers who use closed-circuit oxygen diving apparatus undergo part of their training during the night hours. The greatest risk involved in diving with such apparatus is the development of central nervous system oxygen toxicity (CNS-OT). We investigated whether the switch from day-to-night activity may be a risk factor for the development of CNS-OT using a diurnal animal model, the fat sand rat (Psammomys obesus). Animals were kept on a 12:12 light-dark schedule (6 a.m. to 6 p.m. at 500 lx). The study included two groups: (1) Control group: animals were kept awake and active during the day, between 09:00 and 15:00. (2) Experimental group: animals were kept awake and active during the night, between 21:00 and 03:00, when they were exposed to dim light in order to simulate the conditions prevalent during combat diver training. This continued for a period of 3 weeks, 5 days a week. On completion of this phase, 6-sulphatoxymelatonin (6-SMT) levels in urine were determined over a period of 24 h. Animals were then exposed to hyperbaric oxygen (HBO). To investigate the effect of acute melatonin administration, melatonin (50 mg/kg) or its vehicle was administered to the animals in both groups 20 min prior to HBO exposure. After the exposure, the activity of superoxide dismutase, catalase and glutathione peroxidase was measured, as were the levels of neuronal nitric oxide synthase (nNOS) and overall nitrotyrosylation in the cortex and hippocampus. Latency to CNS-OT was significantly reduced after the transition from day-to-night activity. This was associated with alterations in the level of melatonin metabolites secreted in the urine. Acute melatonin administration had no effect on latency to CNS-OT in either of the groups. Nevertheless, the activity of superoxide dismutase and catalase, as well as nitrotyrosine and nNOS levels, were altered in the hippocampus following melatonin administration. On the basis of these results, we suggest that a switch from diurnal to nocturnal activity may represent an additional risk factor for the development of CNS-OT. Utilizing a diurnal animal model may contribute to our understanding of the heightened risk of developing CNS-OT when diving with closed-circuit oxygen apparatus at night.

The Effect of Aging on the Ventilatory Response to Wearing a Chemical, Biological, Radiological, and Nuclear Hood Respirator at Rest and During Mild Exercise.

BACKGROUND: Structural changes in the human body resulting from aging may affect the response to altered levels of O2 and CO2. An abnormal ventilatory response to a buildup of CO2 in the inspired air due to rebreathing may result in adverse effects, which will impair the individual's ability to function under stress. The purpose of this study was to evaluate the effect of age on the respiratory response to wearing an escape hood at rest and during mild exercise. METHODS: Subjects were seven healthy, young adult males (20-30 years) and seven healthy, middle-aged males (45-65 years). Inspired CO2 and O2, breathing pattern (tidal volume [VT] and breathing frequency [F]), and mouth inspiratory and expiratory pressures, were measured at rest and during mild exercise (50 w) while wearing the CAPS 2000 escape hood (Shalon Chemical Industries and Supergum-Rubber and Plastic Technology, Tel Aviv, Israel). FINDINGS: Resting inspired CO2 was higher in the middle-aged group compared with the young group (2.25% ± 0.42% and 1.80% ± 0.34%, respectively; p < 0.05). Breathing pattern in the middle-aged group tended to be shallower and faster compared with the young group (VT: 0.69 ± 0.27 L and 0.79 ± 0.32 L, respectively; F: 14.7 ± 4.0 breaths/min and 12.4 ± 2.8 breaths/min, respectively). During exercise, there was a trend toward a high inspired CO2 in the middle-aged group compared with the young group (2.18% ± 0.40% CO2 and 1.94% ± 0.70% CO2, respectively). A correlation was found between age and inspired CO2 when wearing the escape hood (r2 = 0.375; p < 0.05). DISCUSSION: The age-related decrease in pulmonary function, together with the finding in this study of a higher inspired CO2 in middle-aged subjects wearing the CAPS 2000, may represent a greater risk for persons of middle age wearing an escape hood. RECOMMENDATIONS: On the basis of this study, it would appear reasonable to recommend that new respirators be evaluated on subjects from different age groups, to ensure the safety of both young and old.

Evidence for the infiltration of gas bubbles into the arterial circulation and neuronal injury following "yo-yo" dives in pigs.

"Yo-yo" diving may place divers at a greater risk of neurologic decompression illness (DCI). Using a rat model, we previously demonstrated that "yo-yo" diving has a protective effect against DCI. In the current study, we evaluated the risk of neurologic DCI following "yo-yo" dives in a pig model. Pigs were divided into four groups. The Control group (group A) made a square dive, without excursions to the surface ("peeps"). Group B performed two "peeps," group C performed four "peeps," and group D did not dive at all. All dives were conducted on air to 5 atm absolute, for 30-min bottom time. Echocardiography was performed to detect cardiac gas bubbles before the dive, immediately after, and at 90-min postdive. Motor performance was observed during the 5-h postdive period. Symptoms increased dramatically following a dive with four "peeps." Gas bubbles were detected in the right ventricle of all animals except for the sham group and in the left ventricle only after the four-peep dive. Neuronal cell injury was found in the spinal cord in each of the three experimental groups, tending to decrease with an increase in the number of "peeps." A four-peep "yo-yo" dive significantly increased the risk of neurologic DCI in pigs. Following a four-peep dive, we detected a higher incidence of bubbles in the left ventricle, supporting the common concern regarding an increased risk of neurologic DCI, albeit there was no direct correlation with the frequency of "red neurons" in the spinal cord.

Evaluating the risk of decompression sickness for a yo-yo dive using a rat model.

PURPOSE: The frequent ascents made during yo-yo diving may contribute to gas bubble clearance but paradoxically may also increase the risk of central nervous system decompression illness (DCI). We evaluated the risk of DCI due to yo-yo dives with very short surface intervals, using a controlled animal model. METHODS: Dives were conducted on air to a depth of 90 meters (10 atmospheres absolute) for 32 minutes of bottom time, at a descent/ascent rate of 10 meters/ minute. Sprague-Dawley rats weighing ~ 300 grams were divided randomly into three groups. Group A performed a square dive protocol without any surface intervals, Group B conducted a protocol that included two surface intervals during the dive, and Group C performed a protocol with three surface intervals. Ascent/descent rate for surface intervals, each lasting one minute, was also 10 meters/minute. RESULTS: Manifestations of DCI were observed in 13 of 16 animals in Group A (81.3%), six of 12 in Group B (58.3%), and two of 12 in Group C (16.7%). Mortality rates were similar in all groups. CONCLUSIONS: Surface intervals during dives breathing air significantly reduced DCI risk in the rat. Further studies are required using a larger animal model to reinforce the results of the present investigation.

Evidence for the initiation of decompression sickness by exposure to intense underwater sound.

Mass stranding of cetaceans (whales and dolphins), in close association with the activity of naval sonar systems, has been reported on numerous occasions. Necropsy showed bubble-associated lesions similar to those described in human decompression sickness (DCS). We examined the hypothesis that exposure to underwater sound may potentiate DCS. Rats were subjected to immersion and simulated dives with and without simultaneous acoustic transmissions at pressure levels and frequencies of 204 dB/8 kHz and 183.3 dB/15 kHz. DCS severity was assessed using the rotating wheel method. Recording of somatosensory evoked potentials (SSEPs) was employed under general anesthesia as an electrophysiological measure of neurologic insult. A significantly higher rate of decompression sickness was found among animals exposed to the 204-dB/8-kHz sound field. Significantly higher pathological SSEPs scores were noted for both underwater sound protocols. Pathological SSEPs scores in animals immersed during the acoustic transmissions, but without changes in ambient pressure, were comparable to those observed in animals exposed to the dive profile. The results demonstrate induction of neurological damage by intense underwater sound during immersion, with a further deleterious effect when this was combined with decompression stress. The study outcome has potential implications for human diving safety and may provide an explanation for the mass stranding of cetaceans purportedly associated with sonar activity.

Alteration of blood glucose levels in the rat following exposure to hyperbaric oxygen.

Findings regarding blood glucose level (BGL) on exposure to hyperbaric oxygen (HBO) are contradictory. We investigated the influence of HBO on BGL, and of BGL on latency to central nervous system oxygen toxicity (CNS-OT). The study was conducted on five groups of rats: Group 1, exposure to oxygen at 2.5 atmospheres absolute (ATA), 90 min/day for 7 days; Group 2, exposure to oxygen once a week from 2 to 6 ATA in increments of 1 ATA/wk, for a period of time calculated as 60% of the latency to CNS-OT (no convulsions); Group 3, exposure to 6 ATA breathing a gas mixture with a pO2 of 0.21; Group 4, received 10 U/kg insulin to induce hypoglycemia before exposure to HBO; Group 5, received 33% glucose to induce hyperglycemia before exposure to HBO. Blood samples were drawn before and after exposures for measurement of BGL. No change was observed in BGL after exposure to oxygen at 2.5 ATA, 90 min/day for 7 days. BGL was significantly elevated after exposure to oxygen at 6 ATA until the appearance of convulsions, and following exposure to 4, 5, and 6 ATA without convulsions (P < 0.01). No change was observed in BGL after exposure to 6 ATA breathing a gas mixture with a pO2 of 0.21. Hypoglycemia shortened latency to CNS oxygen toxicity, whereas hyperglycemia had no effect. Our results demonstrate an influence of HBO exposure on elevation of BGL, starting at 4 ATA. This implies that BGL may serve as a marker for the generation of CNS-OT.

Brief screening test of ventilatory sensitivity to CO2 cannot replace the mandatory test for susceptibility to CNS oxygen toxicity.

Central nervous system oxygen toxicity is a major risk in closed-circuit diving, and the risk increases with elevation of the inspired carbon dioxide (CO2). Mandatory tests for CO2 retention and detection are common practice at the Israel Naval Medical Institute, for the instruction and selection of combat divers at an advanced stage in their training. Read test is a simpler test of the ventilatory response to CO2. Positive correlation between parameters from Read and mandatory tests, enable conducting the test at an earlier stage in diving candidates. In the mandatory test, divers (n = 45) breathing various levels of CO2 in oxygen, and tested for the detection and retention of CO2 reported their sensations. In the Read test, we recorded end-tidal CO2 and ventilation in subjects as they rebreathed from rubber bag. The slope of ventilation was calculated as a function of end-tidal CO2. There was low correlation between any of the parameters from our test and the Read test. There was low insignificant correlation between any parameter from the Read test and detection or retention of CO2. We cannot use the Read test as a test for CO2 retention or detection at an earlier stage in diving candidates.

A comparison of factors involved in the development of central nervous system and pulmonary oxygen toxicity in the rat.

Central nervous system oxygen toxicity (CNS-OT) can occur in humans at pressures above 2atmospheres absolute (ATA), and above 4.5ATA in the rat. Pulmonary oxygen toxicity appears at pressures above 0.5ATA. We hypothesized that exposure to mild HBO following extreme exposure might provide protection against CNS, but not pulmonary oxygen toxicity. We measured the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), and nitrotyrosine and nNOS levels in the brain and lung in the following groups: (1) Sham rats, no pressure exposure (SHAM); (2) Exposure to 6ATA oxygen for 60% of latency to CNS-OT (60%LT); (3) Exposure to 6ATA for 60% of latency to CNS-OT, followed by 20min at 2.5ATA for recovery (REC); (4) Exposure to 6ATA for 60% of latency to CNS-OT, followed by 20min at 2.5ATA oxygen and a subsequent increase in pressure to 6ATA until the appearance of convulsions (CONV); (5) Control rats exposed to 6ATA until the appearance of convulsions (C). SOD and CAT activity were reduced in both brain and lung in the REC group. GPX activity was reduced in the hippocampus in the REC group, but not in the cortex or the lung. nNOS levels were reduced in the hippocampus in the REC group. Contrary to our hypothesis, no difference was observed between the brain and the lung for the factors investigated. We suggest that at 2.5ATA and above, CNS and pulmonary oxygen toxicity may share similar mechanisms.

Hyperbaric oxygen preconditioning protects rats against CNS oxygen toxicity.

We examined the hypothesis that repeated exposure to non-convulsive hyperbaric oxygen (HBO) as preconditioning provides protection against central nervous system oxygen toxicity (CNS-OT). Four groups of rats were used in the study. Rats in the control and the negative control (Ctl-) groups were kept in normobaric air. Two groups of rats were preconditioned to non-convulsive HBO at 202 kPa for 1h once every other day for a total of three sessions. Twenty-four hours after preconditioning, one of the preconditioned groups and the control rats were exposed to convulsive HBO at 608 kPa, and latency to CNS-OT was measured. Ctl- rats and the second preconditioned group (PrC-) were not subjected to convulsive HBO exposure. Tissues harvested from the hippocampus and frontal cortex were evaluated for enzymatic activity and nitrotyrosine levels. In the group exposed to convulsive oxygen at 608 kPa, latency to CNS-OT increased from 12.8 to 22.4 min following preconditioning. A significant decrease in the activity of glutathione reductase and glucose-6-phosphate dehydrogenase, and a significant increase in glutathione peroxidase activity, was observed in the hippocampus of preconditioned rats. Nitrotyrosine levels were significantly lower in the preconditioned animals, the highest level being observed in the control rats. In the cortex of the preconditioned rats, a significant increase was observed in glutathione S-transferase and glutathione peroxidase activity. Repeated exposure to non-convulsive HBO provides protection against CNS-OT. The protective mechanism involves alterations in the enzymatic activity of the antioxidant system and lower levels of peroxynitrite, mainly in the hippocampus.

Women candidates for diving with oxygen-enriched gas mixtures have a lower end tidal CO2 than men during moderate exercise.

We have previously determined the thresholds for CO2 detection (conscious recognition of elevated CO2) and retention in male divers, beyond which a diving candidate should not continue his diving activity due to an increased risk of CNS oxygen toxicity. The purpose of the present study was to establish whether there is a difference in end tidal PCO2 between male and female divers who use oxygen-enriched gas mixtures. Ventilatory and perceptual responses to variations in inspired CO2 (range 0-42 mm Hg) were assessed during moderate exercise in 18 males and 18 females. End tidal PCO2 was lower in the female divers when breathing oxygen with 42 mm Hg CO2 (58.2±3.0 mm Hg vs. 61.5±4.5 mm Hg, P<0.03). These results suggest that female divers have a lower end tidal CO2 than males when breathing a hyperoxic gas mixture during exercise, which might imply that women are less susceptible to CNS oxygen toxicity than men.

Use of a fast transcutaneous CO2 detector to evaluate escape hoods: the "CAPS 2000" with the inlet valves removed from the nose-cup as a test case.

INTRODUCTION: The traditional method used to evaluate escape masks has been to examine the composition of the inspired gas, although arterial carbon dioxide (CO2) and oxygen (O2) would be more relevant physiological parameters. The recent development of reliable, fast-responding transcutaneous CO2 detectors makes it possible to evaluate arterial CO2 and O2 saturation. The CAPS 2000 escape mask was designed to protect the head and respiratory system from chemical or biological attack. The question arises of whether there might be a risk of dangerous hypoxia-hypercapnia in rebreathing from the mask because of leakage of the expired gas from the nose-cup into the hood, although theoretical considerations rule this out. We studied a worst case scenario. METHODS: Nine subjects wore the CAPS 2000 for 15 minutes after removal of the inspiratory valves. A mass spectrometer and transcutaneous sensor were used to measure O2 and CO2, arterial O2 saturation, and arterial partial pressure of CO2 (PCO2). RESULTS: Blood oxygen saturation decreased from an initial value of 98.4% to 96.2% at 2 minutes, subsequently rising and stabilizing at a level similar to control. Subcutaneous PCO2 rose from the control level of 36 to 43 torr after 5 minutes, then decreased to 42 torr and stabilized at that level. Inspired PO2 dropped from 21% to 16% at 3 to 4 minutes, rose to 17% at 8 minutes, and stabilized thereafter. Inspired PCO2 rose to 3% in the first minute and continued to rise to 3.5% at 3 minutes, after which it slowly decreased to 3% and stabilized at that level. DISCUSSION: The transcutaneous CO2 detector provided a true indication of the physiological state of the subject, and these parameters are sufficient on their own for the evaluation of breathing masks. CO2 and O2 did not reach dangerous levels with the inspiratory valves removed from the CAPS 2000 mask.

Prolonged latency to CNS-O2 toxicity induced by heat acclimation in rats is associated with increased antioxidative defenses and metabolic energy preservation.

We have previously shown that heat acclimation provides protection against central nervous system oxygen toxicity (CNS-OT). This was well correlated with increased levels of heat shock protein 72 (HSP72). We now examine other antioxidative defenses against CNS-OT that are correlated with heat acclimation. Two groups of male Sprague-Dawley rats were used. The heat-acclimated group (HA) was exposed for 4 wk to 32°C, and the control group (C) was maintained at 24°C. At the end of the acclimation period, rats were exposed to oxygen at 608 kPa. EEG was recorded continuously until appearance of the first electrical discharge. Brain samples were taken from each group after exposure to pressure. Levels of the antioxidant enzymes CuZnSOD, MnSOD, catalase, and glutathione peroxidase, as well as levels of HSP72, were quantified by Western blot. Comparative proteome analysis of the brains of HA and C rats was carried out using two-dimensional electrophoresis and mass spectrometry to define protein spot alterations. Levels of HSP72 and CuZnSOD were higher in HA rats. Levels of the other antioxidant enzymes were not affected significantly by heat acclimation. Differences in the levels of four protein spots identified as α-synuclein, valosin-containing protein, adenylate kinase 1 (AK1), and the mitochondrial H+-ATP synthase α subunit were found between HA and C rats. We conclude that elevation of HSP72, CuZnSOD, AK1, and the mitochondrial H+-ATP synthase α subunit and possible phosphorylation of α-synuclein--all proteins involved in oxidative stress or energy conservation--might contribute to the prolongation of latency to CNS-OT induced by heat acclimation.

Do hyperbaric oxygen-induced seizures cause brain damage?

It is commonly accepted that hyperbaric oxygen-induced seizures, the most severe manifestation of central nervous system oxygen toxicity, are harmless. However, this hypothesis has not been investigated in depth. We used apoptotic markers to determine whether cells in the cortex and hippocampus were damaged by hyperbaric oxygen-induced seizures in mice. Experimental animals were exposed to a pressure of 6 atmospheres absolute breathing oxygen, and were randomly assigned to two groups sacrificed 1h after the appearance of seizures or 7 days later. Control groups were not exposed to hyperbaric oxygen. Caspase 9, caspase 3, and cytochrome c were used as apoptotic markers. These were measured in the cortex and the hippocampus, and compared between the groups. Levels of caspase 3, cytochrome c, and caspase 9 in the hippocampus were significantly higher in the hyperbaric oxygenexposed groups compared with the control groups 1 week after seizures (p<0.01). The levels of two fragments of caspase 9 in the cortex were higher in the control group compared with the hyperbaric oxygen-exposed group 1h after seizures (p<0.01). Hyperbaric oxygen-induced seizures activate apoptosis in the mouse hippocampus. The reason for the changes in the cortex is not understood. Further investigation is necessary to elucidate the mechanism underlying these findings and their significance.

Flow resistance, work of breathing of humidifiers, and endotracheal tubes in the hyperbaric chamber.

Humidification of inspired gas is critical in ventilated patients, usually achieved by heat and moisture exchange devices (HMEs). HME and the endotracheal tube (ETT) add airflow resistance. Ventilated patients are sometimes treated in hyperbaric chambers. Increased gas density may increase total airway resistance, peak pressures (PPs), and mechanical work of breathing (WOB). We tested the added WOB imposed by HMEs and various sizes of ETT under hyperbaric conditions. We mechanically ventilated 4 types of HMEs and 3 ETTs at 6 minute ventilation volumes (7-19.5 L/min) in a hyperbaric chamber at pressures of 1 to 6 atmospheres absolute (ATA). Peak pressure increased with increasing chamber pressure with an HME alone, from 2 cm H2O at 1 ATA to 6 cm H(2)O at 6 ATA. Work of breathing was low at 1 ATA (0.2 J/L) and increased to 1.2 J/L at 6 ATA at minute ventilation = 19.5 L/min. Connecting the HME to an ETT increased PP as a function of peak flow and chamber pressure. Reduction of the ETT diameter (9 > 8 > 7.5 mm) and increase in chamber pressure increased the PP up to 27.7 cm H2O, resistance to 33.2 cmH2O*s/L, and WOB to 3.76 J/L at 6 ATA with a 7.5-mm EET. These are much greater than the usually accepted critical peak pressures of 25 cm H2O and WOB of 1.5 to 2.0 J/L. Endotracheal tubes less than 8 mm produce significant added WOB and airway pressure swings under hyperbaric conditions. The hyperbaric critical care clinician is advised to use the largest possible ETT. The tested HMEs add negligible resistance and WOB in the chamber.

Oxygen pretreatment as protection against decompression sickness in rats: pressure and time necessary for hypothesized denucleation and renucleation.

Pretreatment with HBO at 300-500 kPa for 20 min reduced the incidence of decompression sickness (DCS) in a rat model. We investigated whether this procedure would be effective with lower oxygen pressures and shorter exposure, and tried to determine how long the pretreatment would remain effective. Rats were pretreated with oxygen at 101 or 203 kPa for 20 min and 304 kPa for 5 or 10 min. After pretreatment, the animals were exposed to air at 1,013 kPa for 33 min followed by fast decompression. Pretreatment at 101 or 203 kPa for 20 min and 304 kPa for 10 min significantly reduced the number of rats with DCS to 45%, compared with 65% in the control group. However, after pretreatment at 304 kPa for 5 min, 65% of rats suffered DCS. When pretreatment at 304 kPa for 20 min was followed by 2 h in normobaric air before compression and decompression, the outcome was worse, with 70-90% of the animals suffering DCS. This is probably due to the activation of "dormant" micronuclei. The risk of DCS remained lower (43%) when pretreatment with 100% O(2) at normobaric pressure for 20 min was followed by a 2 h interval in normobaric air (but not 6 or 24 h) before the hyperbaric exposure. The loss of effectiveness after a 6 or 24 h interval in normobaric air is related to micronuclei rejuvenation. Although pretreatment with hyperbaric O(2) may have an advantage over normobaric hyperoxia, decompression should not intervene between pretreatment and the dive.

Personal CO2 scrubbing device for use in a disabled submarine.

INTRODUCTION: In the sunken submarine, a breakdown in the power supply can disrupt the provision of fresh air and the absorption of CO2. A personal device based on a breathing mask and the soda lime canisters used in the submarine is proposed for CO2 absorption. METHODS: In an unmanned experiment, a breathing simulator provided a flow of air at 8.7 L x min(-1) and a carbon dioxide output of 20.9 L x h(-1), which passed through either one or two 3.8-kg canisters of soda lime. In the manned experiment, four subjects wore the breathing mask, which was connected to two 3.8-kg canisters of soda lime placed in a bag, and remained for 24 h in a sealed hyperbaric chamber. They inspired the chamber atmosphere and expired via the canisters. RESULTS: In the unmanned experiment, the concentration of CO2 when a single canister was used reached 1% after 8 h, 2% after 22 h, and 2.5% after 37 h. With two canisters connected in sequence, the concentration of CO2 reached 1% after 48 h, while the pressure at the entrance to the canisters did not exceed 0.7 cm H2O. In the manned experiment, the CO2 concentration decreased over the first 12 h from its initial value of 1.3%, stabilizing during sleep at 0.75%. DISCUSSION: The personal carbon dioxide absorption device lowered the ambient CO2 level over a period of 24 h, and could maintain this level for a further 24 h. Keeping CO2 at a low level has an advantage over the peaks of 3% obtained with absorbent LiOH curtains, where elevated pressure and increased P(CO2) may have an adverse effect on the survivors. Some of the crew can remain active without using the device, while the others do the job of clearing the carbon dioxide for the whole crew.

Hyperbaric oxygen pretreatment reduces the incidence of decompression sickness in rats.

We have previously hypothesised that the number of bubbles evolving during decompression from a dive, and therefore the incidence of decompression sickness (DCS), might be reduced by pretreatment with hyperbaric oxygen (HBO). The inert gas in the gas micronuclei would be replaced by oxygen, which would subsequently be consumed by the mitochondria. This has been demonstrated in the transparent prawn. To investigate whether our hypothesis holds for mammals, we pretreated rats with HBO at 304, 405, or 507 kPa for 20 min, after which they were exposed to air at 1,013 kPa for 33 min and decompressed at 202 kPa/min. Twenty control rats were exposed to air at 1,013 kPa for 32 min, without HBO pretreatment. On reaching the surface, the rat was immediately placed in a rotating cage for 30 min. The animal's behaviour enabled us to make an early diagnosis of DCS according to accepted symptoms. Rats were examined again after 2 and 24 h. After 2 h, 65% of the control rats had suffered DCS (45% were dead), whereas 35% had no DCS. HBO pretreatment at 304, 405 and 507 kPa significantly reduced the incidence of DCS at 2 h to 40, 40 and 35%, respectively. Compared with the 45% mortality rate in the control group after 24 h, in all of the pretreated groups this was 15%. HBO pretreatment is equally effective at 304, 405 or 507 kPa, bringing about a significant reduction in the incidence of DCS in rats decompressed from 1,013 kPa.