Biophysical basis for inner ear decompression sickness.

Isolated inner ear decompression sickness (DCS) is recognized in deep diving involving breathing of helium-oxygen mixtures, particularly when breathing gas is switched to a nitrogen-rich mixture during decompression. The biophysical basis for this selective vulnerability of the inner ear to DCS has not been established. A compartmental model of inert gas kinetics in the human inner ear was constructed from anatomical and physiological parameters described in the literature and used to simulate inert gas tensions in the inner ear during deep dives and breathing-gas substitutions that have been reported to cause inner ear DCS. The model predicts considerable supersaturation, and therefore possible bubble formation, during the initial phase of a conventional decompression. Counterdiffusion of helium and nitrogen from the perilymph may produce supersaturation in the membranous labyrinth and endolymph after switching to a nitrogen-rich breathing mixture even without decompression. Conventional decompression algorithms may result in inadequate decompression for the inner ear for deep dives. Breathing-gas switches should be scheduled deep or shallow to avoid the period of maximum supersaturation resulting from decompression.     

Role of oxygen in the production of human decompression sickness

In the calculation of decompression schedules, it is commonly assumed that only the inert gas needs to be considered; all inspired O2 is ignored. Animal experiments have shown that high O2 can increase risk of serious decompression sickness (DCS). A trial was performed to assess the relative risks of O2 and N2 in human no-decompression dives. Controlled dives (477) of 30- to 240-min duration were performed with subjects breathing mixtures with low (0.21-0.38 ATA) or high (1.0-1.5 ATA) Po2. Depths were chosen by a sequential dose-response format. Only 11 cases of DCS and 18 cases of marginal symptoms were recorded despite exceeding the presently accepted no-decompression limits by greater than 20%. Analysis by maximum likelihood showed a shallow dose-response curve for increasing depth. O2 was estimated to have zero influence on DCS risk, although data variability still allows a slight chance that O2 could be 40% as effective as N2 in producing a risk of DCS. Consideration of only inert gases is thus justified in calculating human decompression tables.     

Predicting the time of occurrence of decompression sickness.

Probabilistic models and maximum likelihood estimation have been used to predict the occurrence of decompression sickness (DCS). We indicate a means of extending the maximum likelihood parameter estimation procedure to make use of knowledge of the time at which DCS occurs. Two models were compared in fitting a data set of nearly 1,000 exposures, in which greater than 50 cases of DCS have known times of symptom onset. The additional information provided by the time at which DCS occurred gave us better estimates of model parameters. It was also possible to discriminate between good models, which predict both the occurrence of DCS and the time at which symptoms occur, and poorer models, which may predict only the overall occurrence. The refined models may be useful in new applications for customizing decompression strategies during complex dives involving various times at several different depths. Conditional probabilities of DCS for such dives may be reckoned as the dive is taking place and the decompression strategy adjusted to circumstance. Some of the mechanistic implications and the assumptions needed for safe application of decompression strategies on the basis of conditional probabilities are discussed.     

REPETITIVE SHALLOW DIVES POSE DECOMPRESSION RISK IN DEEP-DIVING BEAKED WHALES

The impact of naval sonar on beaked whales is of increasing concern. In recent years the presence of gas and fat embolism consistent with decompression sickness (DCS) has been reported through postmortem analyses on beaked whales that stranded in connection with naval sonar exercises. In the present study, we use basic principles of diving physiology to model nitrogen tension and bubble growth in several tissue compartments during normal diving behavior and for several hypothetical dive profiles to assess the risk of DCS. Assuming that normal diving does not cause nitrogen tensions in excess of those shown to be safe for odontocetes, the modeling indicates that repetitive shallow dives, perhaps as a consequence of an extended avoidance reaction to sonar sound, can indeed pose a risk for DCS and that this risk should increase with the duration of the response. If the model is correct, then limiting the duration of sonar exposure to minimize the duration of any avoidance reaction therefore has the potential to reduce the risk of DCS.     

Decompression sickness in the rat following a dive on trimix: recompression therapy with oxygen vs. heliox and oxygen.

Trimix (a mixture of helium, nitrogen, and oxygen) has been used in deep diving to reduce the risk of high-pressure nervous syndrome during compression and the time required for decompression at the end of the dive. There is no specific recompression treatment for decompression sickness (DCS) resulting from trimix diving. Our purpose was to validate a rat model of DCS on decompression from a trimix dive and to compare recompression treatment with oxygen and heliox (helium-oxygen). Rats were exposed to trimix in a hyperbaric chamber and tested for DCS while walking in a rotating wheel. We first established the experimental model, and then studied the effect of hyperbaric treatment on DCS: either hyperbaric oxygen (HBO) (1 h, 280 kPa oxygen) or heliox-HBO (0.5 h, 405 kPa heliox 50%-50% followed by 0.5 h, 280 kPa oxygen). Exposure to trimix was conducted at 1,110 kPa for 30 min, with a decompression rate of 100 kPa/min. Death and most DCS symptoms occurred during the 30-min period of walking. In contrast to humans, no permanent disability was found in the rats. Rats with a body mass of 100-150 g suffered no DCS. The risk of DCS in rats weighing 200-350 g increased linearly with body mass. Twenty-four hours after decompression, death rate was 40% in the control animals and zero in those treated immediately with HBO. When treatment was delayed by 5 min, death rate was 25 and 20% with HBO and heliox, respectively.     

Modulation of decompression sickness risk in pigs with caffeine during H(2) biochemical decompression.

In H(2) biochemical decompression, H(2)-metabolizing intestinal microbes remove gas stored in tissues of animals breathing hyperbaric H(2), thereby reducing decompression sickness (DCS) risk. We hypothesized that increasing intestinal perfusion in pigs would increase the activity of intestinal Methanobrevibacter smithii, lowering DCS incidence further. Pigs (Sus scrofa, 17-23 kg, n = 20) that ingested caffeine (5 mg/kg) increased O(2) consumption rate in 1 atm air by ~20% for at least 3 h. Pigs were given caffeine alone or caffeine plus injections of M. smithii. Animals were compressed to 24 atm (20.5-23.1 atm H(2), 0.3-0.5 atm O(2)) for 3 h, then decompressed and observed for signs of DCS. In previous studies, DCS incidence in animals without caffeine treatment was significantly (P < 0.05) lower with M. smithii injections (7/16) than in controls (9/10). However, contrary to our hypothesis, DCS incidence was marginally higher (P = 0.057) in animals that received caffeine and M. smithii (9/10) than in animals that received caffeine but no M. smithii (4/10). More information on gas kinetics is needed before extending H(2) biochemical decompression to humans.     

Decompression outcome following saturation dives with multiple inert gases in rats

This investigation examined the question of whether gas mixtures containing multiple inert gases provide a decompression advantage over mixtures containing a single inert gas. Unanesthetized male albino rats, Rattus norvegicus, were subjected to 2-h simulated dives at depths ranging from 145 to 220 fsw. At pressure, the rats breathed various He-N2-Ar-O2 mixtures (79.1% inert gas-20.9% O2); they were then decompressed rapidly (within 10 s) to surface pressures. The probability of decompression sickness (DCS), measured either as severe bends symptoms or death, was related to the experimental variables in a Hill equation model incorporating parameters that account for differences in the potencies of the three gases and the weight of the animal. The relative potencies of the three gases, which affect the total dose of decompression stress, were determined as significantly different in the following ascending order of potency: He less than N2 less than Ar; some of these differences were small in magnitude. With mixtures, the degree of decompression stress diminished as either N2 or Ar was replaced by He. No obvious advantage or disadvantage of mixtures over the least potent pure inert gas (He) was evident, although limits to the expectation of possible advantage or disadvantage of mixtures were defined. Also, model analysis did not support the hypothesis that the outcome of decompression with multiple inert gases in rats under these experimental conditions can be explained totally by the volume of gas accumulated in the body during a dive.     

Mixed-gas model for predicting decompression sickness in rats.

A mixed-gas model for rats was developed to further explore the role of different gases in decompression and to provide a global model for possible future evaluation of its usefulness for human prediction. A Hill-equation dose-response model was fitted to over 5,000 rat dives by using the technique of maximum likelihood. These dives used various mixtures of He, N(2), Ar, and O(2) and had times at depth up to 2 h and varied decompression profiles. Results supported past findings, including 1) differences among the gases in decompression risk (He < N(2) < Ar) and exchange rate (He > Ar approximately N(2)), 2) significant decompression risk of O(2), and 3) increased risk of decompression sickness with heavier animals. New findings included asymmetrical gas exchange with gas washout often unexpectedly faster than uptake. Model success was demonstrated by the relatively small errors (and their random scatter) between model predictions and actual incidences. This mixed-gas model for prediction of decompression sickness in rats is the first such model for any animal species that covers such a broad range of gas mixtures and dive profiles.     

Effect of inert gas switching at depth on decompression outcome in rats

The present investigation was performed to determine whether inert gas sequencing at depth would affect decompression outcome in rats via the phenomenon of counterdiffusion. Unanesthetized rats (Rattus norvegicus) were subjected to simulated dives in either air, 79% He-21% O2, or 79% Ar-21% O2; depths ranged from 125 to 175 feet of seawater (4.8-6.3 atmospheres absolute). After 1 h at depth, the dive chamber was vented (with depth held constant) over a 5-min period with the same gas as in the chamber (controls) or one of the other two inert gas-O2 mixtures. After the gas switch, a 5- to 35-min period was allowed for gas exchange between the animals and chamber atmosphere before rapid decompression to the surface. Substantial changes in the risk of decompression sickness (DCS) were observed after the gas switch because of differences in potencies (He less than N2 less than Ar) for causing DCS and gas exchange rates (He greater than Ar greater than N2) among the three gases. Based on the predicted gas exchange rates, transient increases or decreases in total inert gas pressure would be expected to occur during these experimental conditions. Because of differences in gas potencies, DCS risk may not directly follow the changes in total inert gas pressure. In fact, a decline in predicted DCS risk may occur even as total inert gas pressure in increasing.     

Using animal data to improve prediction of human decompression risk following air-saturation dives.

To plan for any future rescue of personnel in a disabled and pressurized submarine, the US Navy needs a method for predicting risk of decompression sickness under possible scenarios for crew recovery. Such scenarios include direct ascent from compressed air exposures with risks too high for ethical human experiments. Animal data, however, with their extensive range of exposure pressures and incidence of decompression sickness, could improve prediction of high-risk human exposures. Hill equation dose-response models were fit, by using maximum likelihood, to 898 air-saturation, direct-ascent dives from humans, pigs, and rats, both individually and combined. Combining the species allowed estimation of one, more precise Hill equation exponent (steepness parameter), thus increasing the precision associated with human risk predictions. These predictions agreed more closely with the observed data at 2 ATA, compared with a current, more general, US Navy model, although the confidence limits of both models overlapped those of the data. However, the greatest benefit of adding animal data was observed after removal of the highest risk human exposures, requiring the models to extrapolate.     

Short oxygen prebreathing and intravenous perfluorocarbon emulsion reduces morbidity and mortality in a swine saturation model of decompression sickness.

Disabled submarine (DISSUB) survivors will achieve inert gas tissue saturation within 24 h. Direct ascent to the surface when saturated carries a high risk of decompression sickness (DCS) and death, yet may be necessary during rescue or escape. O(2) has demonstrated benefits in decreasing morbidity and mortality resulting from DCS by enhancing inert gas elimination. Perfluorocarbons (PFCs) also mitigate the effects of DCS by decreasing bubble formation and increasing O(2) delivery. Our hypothesis is that combining O(2) prebreathing (OPB) and PFC administration will reduce the incidence of DCS and death following saturation in an established 20-kg swine model. Yorkshire swine (20 +/- 6.5 kg) were compressed to 5 atmospheres (ATA) in a dry chamber for 22 h before randomization into one of four groups: 1) air and saline, 2) OPB and saline, 3) OPB with PFC given at depth, 4) OPB with PFC given after surfacing. OPB animals received >90% O(2) for 9 min at depth. All animals were returned to the surface (1 ATA) without decompression stops. The incidence of severe DCS < 2 h after surfacing was 96%, 63%, 82%, and 29% for groups 1, 2, 3, and 4, respectively. The incidence of death was 88%, 41%, 54%, and 5% for groups 1, 2, 3, and 4, respectively. OPB combined with PFC administration after surfacing provided the greatest reduction in DCS morbidity and mortality in a saturation swine model. O(2)-related seizure activity before reaching surface did not negatively affect outcome, but further safety studies are warranted.     

Specifics of Gas Bubble Formation and Growth in Tissues during Decompression after Saturation Dives

It is shown that the decompression schedules after saturation diving to the depth of 30 m designed to hold the nitrogen supersaturation for the most “slow” tissues at the acceptable levels is significantly shorter than the decompression schedules with zero supersaturation of these tissues with nitrogen and all dissolved gases. Equality of the risk for decompression sickness (DCS) onset during this decompression schedule to the risk of DCS onset under non-stop ascent to the surface after saturation diving to the depth of 6.1 m indicates that the effect of the high ambient pressure decreases the density of gas bubble seeds in tissues and the growth rate of their total volume. The DCS symptoms in the experienced divers under dangerous decompression profiles not appear due to the lower density of gas bubble seeds in their tissues relatively to the average level inherent to the many of humans.     

Acclimatization to neurological decompression sickness in rabbits

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.     

Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness

Decompression sickness (DCS) with alterations in coagulation system and formation of platelet thrombi occurs when a subject is subjected to a reduction in environmental pressure. Blood platelet consumption after decompression is clearly linked to bubble formation in humans and offers an index for evaluating DCS severity in animal models. Previous studies highlighted a predominant involvement of platelet activation and thrombin generation in bubble-induced platelet aggregation (BIPA). To study the mechanism of the BIPA in DCS, we examined the effect of acetylsalicylic acid (ASA), heparin (Hep), and clopidogrel (Clo), with anti-thrombotic dose pretreatment in a rat model of DCS. Male Sprague-Dawley rats (n = 208) were randomly assigned to one experimental group treated before the hyperbaric exposure and decompression protocol either with ASA (3×100 mg·kg(-1)·day(-1), n = 30), Clo (50 mg·kg(-1)·day(-1), n = 60), Hep (500 IU/kg, n = 30), or to untreated group (n = 49). Rats were first compressed to 1,000 kPa (90 msw) for 45 min and then decompressed to surface in 38 min. In a control experiment, rats were treated with ASA (n = 13), Clo (n = 13), or Hep (n = 13) and maintained at atmospheric pressure for an equivalent period of time. Onset of DCS symptoms and death were recorded during a 60-min observation period after surfacing. DCS evaluation included pulmonary and neurological signs. Blood samples for platelet count (PC) were taken 30 min before hyperbaric exposure and 30 min after surfacing. Clo reduces the DCS mortality risk (mortality rate: 3/60 with Clo, 15/30 with ASA, 21/30 with Hep, and 35/49 in the untreated group) and DCS severity (neurological DCS incidence: 9/60 with Clo, 6/30 with ASA, 5/30 with Hep, and 12/49 in the untreated group). Clo reduced fall in platelet count and BIPA (-4,5% with Clo, -19.5% with ASA, -19,9% with Hep, and -29,6% in the untreated group). ASA, which inhibits the thromboxane A2 pathway, and Hep, which inhibits thrombin generation, have no protective effect on DCS incidence. Clo, a specific ADP-receptor antagonist, reduces post-decompression platelet consumption. These results point to the predominant involvement of the ADP release in BIPA but cannot differentiate definitively between bubble-induced vessel wall injury and bubble-blood component interactions in DCS.     

Oxygen or carbogen breathing before simulated submarine escape.

Raised internal pressure in a distressed submarine increases the risk of bubble formation and decompression illness after submarine escape. The hypothesis that short periods of oxygen breathing before submarine escape would reduce decompression stress was tested, using Doppler-detectable venous gas emboli as a measure. Twelve goats breathed oxygen for 15 min at 0.1 MPa before exposure to a simulated submarine escape profile to and from 2.5 MPa (240 m/seawater), whereas 28 control animals underwent the same dive without oxygen prebreathe. No decompression sickness (DCS) occurred in either of these two groups. Time with high bubble scores (Kisman-Masurel >or=3) was significantly (P < 0.001) shorter in the prebreathe group. In a second series, 30 goats breathed air at 0.2 MPa for 6 h. Fifteen minutes before escape from 2.5 MPa, animals were provided with either air (n = 10), oxygen (n = 12), or carbogen (97.5% O(2) and 2.5% CO(2)) gas (n = 8) as breathing gas. Animals breathed a hyperoxic gas (60% O(2)-40% N(2)) during the escape. Two animals (carbogen group) suffered oxygen convulsions during the escape but recovered on surfacing. Only one case of DCS occurred (carbogen group). The initial bubble score was reduced in the oxygen group (P < 0.001). The period with bubble score of Kisman-Masurel >or=3 was also significantly reduced in the oxygen group (P < 0.001). Oxygen breathing before submarine escape reduces initial bubble scores, although its significance in reducing central nervous system DCS needs to be investigated further.     

Increasing activity of H(2)-metabolizing microbes lowers decompression sickness risk in pigs during H(2) dives.

The risk of decompression sickness (DCS) was modulated by varying the biochemical activity used to eliminate some of the hydrogen (H(2)) stored in the tissues of pigs (19.4 +/- 0.2 kg) during hyperbaric exposures to H(2). Treated pigs (n = 16) received intestinal injections of Methanobrevibacter smithii, a microbe that metabolizes H(2) to water and CH(4). Surgical controls (n = 10) received intestinal injections of saline, and an additional control group (n = 10) was untreated. Pigs were placed in a chamber and compressed to 24 atm abs (20.6-22.9 atm H(2)). After 3 h, the pigs were decompressed and observed for symptoms of DCS for 1 h. Pigs with M. smithii had a significantly lower (P < 0.05) incidence of DCS (44%; 7/16) than all controls (80%; 16/20). The DCS risk decreased with increasing activity of microbes injected (logistic regression, P < 0.05). Thus the supplemental tissue washout of the diluent gas by microbial metabolism was inversely correlated with DCS risk in a dose-dependent manner in this pig model.     

Theoretical evaluation of safety of dives completed by non-stop ascent to surface

Our model of decompression sickness determines the cumulative probability of developing symptoms of this illness by the exponential equation whose index is the integral cumulative risk function of all body tissue lesions by bubbles, F _cum(t) = ΣF _n(t). The underwater dives may be considered as practically safe in the context of this model when the function F _cum(t) during its growth will not exceed some small value F _cum-max = ΣF _n-max. Using hypothetical values of parameters of tissues and functions F _n(t), we calculated the curves depth-duration for practically safe non-stop dives with air and with mixtures of oxygen with helium, neon and argon. Doing so, we obtained the distributions of values F _n-max in regard to the values of inert gas washout half-times from tissues which show that the tissues experienced the largest risks of bubble lesions are different for dives with different duration. The comparison of the indicated curves shows that the short-term dives with air are less dangerous and the long-term dives are more dangerous than the dives with helium-oxygen mixture. At the same time, the least risk of bubble lesions of tissues arises at dives with neon-oxygen mixture and the greatest risk arises at dives with argon-oxygen mixture.     

Effect of N2-He-O2 on decompression outcome in rats after variable time-at-depth dives

No study of decompression sickness has examined both variable gas mixtures and variable time at depth to the point of statistical significance. This investigation examined the effect of N2-He-O2 on decompression outcome in rats after variable time-at-depth dives. Unanesthetized male albino rats were subjected to one of two series of simulated dives: 1) N2-He-O2 dives (20.9% O2) at 175 feet of seawater fsw) and 2) N2-O2 dives (variable percentage of O2; depths from 141 to 207 fsw). Time at depth ranged from 10 to 120 min; rats were then decompressed within 10 s to surface pressure. The probability of decompression sickness (severe bends symptoms or death) was analyzed with a Hill equation model, with parameters for gas potency and equilibrium time for the three gases and weight of the animal. Relative potencies for the three gases were of similar magnitude for bends and statistically different for death in ascending order: O2 less than He less than N2. Estimated gas uptake rates were different. N2 took three to four times as long as He to reach full effect; the rate of O2 appeared to be considerably shorter than that of N2 or He. The large influence of O2 on decompression outcome questions the simplistic view that O2 cannot contribute to the decompression requirement.     

Natural history of severe decompression sickness after rapid ascent from air saturation in a porcine model.

We developed a swine model to describe the untreated natural history of severe decompression sickness (DCS) after direct ascent from saturation conditions. In a recompression chamber, neutered male Yorkshire swine were pressurized to a predetermined depth from 50-150 feet of seawater [fsw; 2.52-5.55 atmospheres absolute (ATA)]. After 22 h, they returned to the surface (1 ATA) at 30 fsw/min (0.91 ATA/min) without decompression stops and were observed. Depth was the primary predictor of DCS incidence (R = 0.52, P < 0.0001) and death (R = 0.54, P < 0.0001). Severe DCS, defined as neurological or cardiopulmonary impairment, occurred in 78 of 128 animals, and 42 of 51 animals with cardiopulmonary DCS died within 1 h after surfacing. Within 24 h, 29 of 30 survivors with neurological DCS completely resolved their deficits without intervention. Pretrial Monte Carlo analysis decreased subject requirement without sacrificing power. This model provides a useful platform for investigating the pathophysiology of severe DCS and testing therapeutic interventions. The results raise important questions about present models of human responses to similar decompressive insults.