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.     

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.     

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.     

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 risk of decompression sickness in humans from outcomes in sheep.

In animals, the response to decompression scales as a power of species body mass. Consequently, decompression sickness (DCS) risk in humans should be well predicted from an animal model with a body mass comparable to humans. No-stop decompression outcomes in compressed air and nitrogen-oxygen dives with sheep (n = 394 dives, 14.5% DCS) and humans (n = 463 dives, 4.5% DCS) were used with linear-exponential, probabilistic modeling to test this hypothesis. Scaling the response parameters of this model between species (without accounting for body mass), while estimating tissue-compartment kinetic parameters from combined human and sheep data, predicts combined risk better, based on log likelihood, than do separate sheep and human models, a combined model without scaling, and a kinetic-scaled model. These findings provide a practical tool for estimating DCS risk in humans from outcomes in sheep, especially in decompression profiles too risky to test with humans. This model supports the hypothesis that species of similar body mass have similar DCS risk.     

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.     

Ventilation-perfusion inhomogeneity increases gas uptake: theoretical modeling of gas exchange.

Ventilation-perfusion (VA/Q) inhomogeneity was modeled to measure its effect on gas exchange in the presence of inspired mixtures of two soluble gases using a two-compartment computer model. Theoretical studies involving a mixture of hypothetical gases with equal solubility in blood showed that the effect of increasing inhomogeneity of distributions of either ventilation or blood flow is to paradoxically increase uptake of the gas with the lowest overall uptake in relation to its inspired concentration. This phenomenon is explained by the concentrating effects that uptake of soluble gases exert on each other in low VA/Q compartments. Repeating this analysis for inspired mixtures of 30% O(2) and 70% nitrous oxide (N(2)O) confirmed that, during "steady-state" N(2)O anesthesia, uptake of N(2)O is predicted to paradoxically increase in the presence of worsening VA/Q inhomogeneity.     

Decompression comparison of helium and hydrogen in rats

Lillo, R. S., E. C. Parker, and W. R. Porter.Decompression comparison of helium and hydrogen in rats.J. Appl. Physiol. 82(3): 892-901, 1997.The hypothesis that there are differences in decompression riskbetween He and H₂ wasexamined in 1,607 unanesthetized male albino rats subjected to dives on2% O₂-balance He or 2%O₂-balanceH₂ (depths  50 ATA, bottom times  60 min). The animals were decompressed to 10.8 ATA with profilesvarying from rapid to slow, with up to four decompression stops of up to 60 min each. Maximum likelihood analysis was used to estimate therelative decompression risk on a per unit pressure basis (termed "potency") and the rate of gas uptake and elimination, bothfactors affecting the decompression sickness risk, from a specific dive profile. H₂ potency for causingdecompression sickness was found to be up to 35% greater than that forHe. Uptake rates were unresolvable between the two gases with the timeconstant (TC) estimated at ~2-3 min, leading to saturation inboth cases in <15 min. Washout of both gases was significantly slowerthan uptake, with He washout (TC ~1.5-3 h) substantially slowerthan H₂ washout (TC ~0.5 h). Itis unknown whether the decompression advantage of the faster washout ofH₂ or the disadvantage of itsincreased potency, observed in the rat, would be important for humandiving.

     

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.     

Gas transport and blood acid-base balance in diving sea snakes.

The values of hemoglobin concentration, Hb-O2 affinity and buffering capacity of the blood of six sea snake species considerably overlap values from terrestrial squamates. Decreased blood pH had little effect on the P50 but increased the n-value of Hb-O2 equilibrium curves. The O2 saturation of blood in the dorsal aorta varied between about 30 and 70% during voluntary diving in Acalyptophis peronii and Lapemis hardwickii. Voluntary dives ended when the lung PP02 was about 50 mm Hg and the arterial PO2 about 30 mm Hg indicating that roughly half of the O2 reserves had been used. In conjunction with relatively stable blood lactate concentration and pH, this indicates that voluntary dives occurred largely aerobically. In contrast, forced dives resulted in depletion of O2 reserves and large changes in blood acid-base balance. Long recovery periods following forced dives are inconsistent with field observations and thus suggest that extensive anaerobic metabolism does not normally occur in sea snakes. Bradycardia was not evident during forced dives. Large differences in PO2 between the lung and dorsal aorta indicated considerable right to left shunting either in the heart or in the lung. Venous blood represented over 50% of the systemic flow when there was considerable O2 in the lung. Therefore blood PO2 may remain relatively low despite elevated lung PO2 resulting from diving. In view of substantial capability for extra-pulmonary gas exchange, high shunting reduces the possibility of losing O2 through the skin and also may help prevent decompression sickness following deep dives.     

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.     

On the likelihood of decompression sickness during H(2) biochemical decompression in pigs.

A probabilistic model was used to predict decompression sickness (DCS) outcome in pigs during exposures to hyperbaric H(2) to quantify the effects of H(2) biochemical decompression, a process in which metabolism of H(2) by intestinal microbes facilitates decompression. The data set included 109 exposures to 22-26 atm, ca. 88% H(2), 9% He, 2% O(2), 1% N(2), for 0.5-24 h. Single exponential kinetics described the tissue partial pressures (Ptis) of H(2) and He at time t: Ptis = integral (Pamb - Ptis). tau(-1) dt, where Pamb is ambient pressure and tau is a time constant. The probability of DCS [P(DCS)] was predicted from the risk function: P(DCS) = 1 - e(-r), where r = integral (Ptis(H(2)) + Ptis(He) - Thr - Pamb). Pamb(-1) dt, and Thr is a threshold parameter. Inclusion of a parameter (A) to estimate the effect of H(2) metabolism on P(DCS): Ptis(H(2)) = integral (Pamb - A - Ptis(H(2))). tau(-1) dt, significantly improved the prediction of P(DCS). Thus lower P(DCS) was predicted by microbial H(2) metabolism during H(2) biochemical decompression.     

Effects of temperature and composition on the viscosity of respiratory gases

The steady-state sensitivity of resistance pneumotachographs is proportional to viscosity. Dynamic characteristics of pneumotachographs, pressure transducers, and mass spectrometers are also viscosity dependent. We derive linear equations to approximate the viscosities of O2, N2, CO2, H2O, He, N2O, and Ar for temperatures between 20 and 40 degrees C by using published viscosity data and a nonlinear extrapolation equation. We verify the accuracy of the extrapolation equation by comparison with published data. Our linear equations for pure gas viscosities yield standard errors less than 0.35 microP. We also compare a nonlinear equation for calculating the viscosities of mixtures of gases with published measured viscosities of dry air, humid air, and He-O2 and N2-CO2 mixtures. The maximum difference between published and calculated values is 1.3% for 10% CO2 in N2. All other differences are less than 0.38%. For saturated humid air at 35 degrees C, a linear concentration-weighted combination of viscosities differs from our nonlinear equation by 4.9, 2.1, and 1.7% at barometric pressures of 32, 83, and 100 kPa, respectively. By use of our method, the viscosity of normal respiratory gases can be calculated to within 1% of measured values.     

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.     

Growth responses of Neurospora crassa to increased partial pressures of the noble gases and nitrogen

Buchheit, R. G. (Union Carbide Corp., Tonawanda, N.Y.), H. R. Schreiner, and G. F. Doebbler. Growth responses of Neurospora crassa to increased partial pressures of the noble gases and nitrogen. J. Bacteriol. 91:622-627. 1966.-Growth rate of the fungus Neurospora crassa depends in part on the nature of metabolically "inert gas" present in its environment. At high partial pressures, the noble gas elements (helium, neon, argon, krypton, and xenon) inhibit growth in the order: Xe > Kr> Ar > Ne > He. Nitrogen (N(2)) closely resembles He in inhibitory effectiveness. Partial pressures required for 50% inhibition of growth were: Xe (0.8 atm), Kr (1.6 atm), Ar (3.8 atm), Ne (35 atm), and He ( approximately 300 atm). With respect to inhibition of growth, the noble gases and N(2) differ qualitatively and quantitatively from the order of effectiveness found with other biological effects, i.e., narcosis, inhibition of insect development, depression of O(2)-dependent radiation sensitivity, and effects on tissue-slice glycolysis and respiration. Partial pressures giving 50% inhibition of N. crassa growth parallel various physical properties (i.e., solubilities, solubility ratios, etc.) of the noble gases. Linear correlation of 50% inhibition pressures to the polarizability and of the logarithm of pressure to the first and second ionization potentials suggests the involvement of weak intermolecular interactions or charge-transfer in the biological activity of the noble gases.     

A model of extravascular bubble evolution: effect of changes in breathing gas composition.

Observations of bubble evolution in rats after decompression from air dives (O. Hyldegaard and J. Madsen. Undersea Biomed. Res. 16: 185-193, 1989; O. Hyldegaard and J. Madsen. Undersea Hyperbaric Med. 21: 413-424, 1994; O. Hyldegaard, M. Moller, and J. Madsen. Undersea Biomed. Res. 18: 361-371, 1991) suggest that bubbles may resolve more safely when the breathing gas is a heliox mixture than when it is pure O(2). This is due to a transient period of bubble growth seen during switches to O(2) breathing. In an attempt to understand these experimental results, we have developed a multigas-multipressure mathematical model of bubble evolution, which consists of a bubble in a well-stirred liquid. The liquid exchanges gas with the bubble via diffusion, and the exchange between liquid and blood is described by a single-exponential time constant for each inert gas. The model indicates that bubbles resolve most rapidly in spinal tissue, in adipose tissue, and in aqueous tissues when the breathing gas is switched to O(2) after surfacing. In addition, the model suggests that switching to heliox breathing may prolong the existence of the bubble relative to breathing air for bubbles in spinal and adipose tissues. Some possible explanations for the discrepancy between model and experiment are discussed.     

Microbial growth modification by compressed gases and hydrostatic pressure

Studies of the growth-modifying actions for Escherichia coli, Saccharomyces cerevisiae, and Tetrahymena thermophila of helium, nitrogen, argon, krypton, xenon, and nitrous oxide led to the conclusion that there are two definable classes of gases. Class 1 gases, including He, N(2), and Ar, are not growth inhibitors; in fact, they can reverse the growth inhibitory action of hydrostatic pressures. Class 2 gases, including Kr, Xe, and N(2)O, are potent growth inhibitors at low pressures. For example, at 24 degrees C, 50% growth-inhibitory pressures of N(2)O were found to be ca. 1.7 MPa for E. coli, 1.0 MPa for S. cerevisiae, and 0.5 MPa for T. thermophila. Class 1 gases could act as potentiators for growth inhibition by N(2)O, O(2), Kr, or Xe. Hydrostatic pressure alone is known to reverse N(2)O inhibition of growth, but we found that it did not greatly alter oxygen toxicity. Therefore, potentiation by class 1 gases appeared to be a gas effect rather than a pressure effect. The temperature profile for growth inhibition of S. cerevisiae by N(2)O revealed an optimal temperature for cell resistance of ca. 24 degrees C, with lower resistance at higher and lower temperatures. Overall, it appeared that microbial growth modification by hyperbaric gases could not be related to their narcotic actions but reflected definably different physiological actions.     

Inert gas enhancement of superoxide radical production.

Two free radical generating systems, xanthine oxidase/hypoxanthine or phenazine methosulfate/NADH, were exposed to air plus He, N2, or Ar at partial pressures ranging from 0.2 to 6.0 MPa, and the rates of production of superoxide, hydroxyl, singlet O2, and H2O2 were measured. All three inert gases acted similarly to enhance the production of superoxide radicals by facilitating interactions between iron and H2O2, or O2 and organic radicals. These reactions occurred at quite low gas partial pressures, only 0.28 MPa, and hydrostatic pressures of up to 6.0 MPa had no effect on radical reactions. Enhanced radical production may be the basis for the inhibition of cellular growth mediated by inert gases, and inert gas enhancement of O2 toxicity.     

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.