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Diving and Environmental Physiology Department, Naval Medical Research Institute, Bethesda, Maryland 20889-5607
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
APPENDIX
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
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 risk
between He and H2 was
examined in 1,607 unanesthetized male albino rats subjected to dives on
2% O2-balance He or 2%
O2-balance
H2 (depths 
50 ATA, bottom times 60 min). The animals were decompressed to 10.8 ATA with profiles
varying from rapid to slow, with up to four decompression stops of up to 60 min each. Maximum likelihood analysis was used to estimate the
relative decompression risk on a per unit pressure basis (termed "potency") and the rate of gas uptake and elimination, both
factors affecting the decompression sickness risk, from a specific dive profile. H2 potency for causing
decompression sickness was found to be up to 35% greater than that for
He. Uptake rates were unresolvable between the two gases with the time
constant (TC) estimated at ~2-3 min, leading to saturation in
both cases in <15 min. Washout of both gases was significantly slower
than uptake, with He washout (TC ~1.5-3 h) substantially slower
than H2 washout (TC ~0.5 h). It
is unknown whether the decompression advantage of the faster washout of
H2 or the disadvantage of its
increased potency, observed in the rat, would be important for human
diving.
decompression sickness; diving; hyperbaric; inert gases
INTRODUCTION COMPRESSED AIR is a satisfactory breathing gas for
almost all shallow water diving and is widely used. Beyond 5 ATA,
however, N2 narcosis begins to
significantly impair an air diver's performance, and working dives
much below 6 ATA are prohibited by narcosis (8). To avoid this problem,
divers generally breathe binary mixtures of He and
O2. However, the deeper dives are
complicated by 1) long decompression
schedules; 2) reduced work capacity
due to the increased work of breathing a dense, highly compressed gas
(21); and 3) a variety of
neurological symptoms collectively known as the high-pressure nervous
syndrome (HPNS; Ref. 2). Small amounts of
N2 have been added experimentally
to He-O2, which have reduced some
of the pronounced HPNS symptoms, but breathing resistance is increased
and the potential for N2 narcosis
recurs. Based on the rationale that
1)
H2 also has some narcotic potency that could antagonize, hence lessen, HPNS and
2)
H2 is one-half as dense as He and
should be easier to breathe, the use of
H2 as a complete or partial
substitute for He has been proposed (4). The recent interest in
H2 as a diving gas has coincided
with the development of technology that overcomes the danger of
H2 flammability, particularly at
great depths where low percentages of
O2 are used in breathing mixtures
(9). These gas mixtures have been safely tested starting in the 1980s
during experimental dives in Europe, particularly France, and were
reasonably successful (13).
An important consideration for using
H2 for diving is the decompression
characteristics of this gas and how it compares to He. Research and
experience indicate that there can be significant differences in risk
among gases for causing decompression sickness (DCS; Refs. 17, 18).
Given the role that bubbles appear to play in DCS, these differences
have been generally attributed to differences in gas properties such as
tissue solubility and diffusivity. For
H2, however, there is an
additional consideration of reactivity within the body. Typical
"inert" diving gases such as
N2 and He are generally considered
to be chemically nonreactive with the tissues. On the other hand, the
conversion of H2 to water through
enzymatic oxidation may be possible (13). Such a process would not only
reduce the decompression time by chemical removal of the gas from the
body but also might increase cold-water tolerance by enhancing body
heat production. However, a recent study suggests that mammalian
tissues do not metabolize H2 even
in a hyperbaric environment (14). Limited experience with human
decompression after H2 diving
suggests that decompression requirements for He and
H2 may be similar (6, 13).
This investigation responds to the need to examine critically the
decompression aspect of H2 by
comparing the decompression risk of He and
H2 in rats with the maximum
likelihood technique (7), which is well suited for analyzing binary
data such as decompression outcome. Based on differences between the
properties of the two gases, the study hypothesis was that there would
be differences in the risk of DCS between He and
H2.
METHODS Summary
The experiments reported herein were conducted according to the principles set forth in the Guide for the Care and Use of Laboratory Animals [DHEW Publication No. (NIH) 86-23, Revised 1985].
Experimental Protocols
Male albino rats (Rattus norvegicus, Sprague-Dawley strain) weighing ~200-300 g were obtained from a local supplier and housed in the Institute's Animal Care Facility for at least 1 wk before use. The animals were allowed access to food and water up until immediately before the dive began.Diving procedures. The experiments were conducted in a facility equipped with special safety features designed for small-animal diving with H2 and He at pressures up to ~60 ATA. The animals were dived on one of two gas mixtures: 1) 2% O2-balance He or 2) 2% O2-balance H2. Both dive mixtures were obtained either commercially or prepared in-house and were confirmed to be within 2.0-2.2% O2 for use.
Immediately before each dive, five animals were individually weighed on a triple-beam balance to the nearest gram and placed in a cylindrical cage (56 cm long, 23 cm diameter), which was then loaded into a hyperbaric chamber (Bethlehem model 183160 HP, Bethlehem, PA). The air-filled chamber was sealed and pressurized with pure He to 10.8 ATA, resulting in an O2 concentration of ~2%. Immediately on reaching 10.8 ATA, a gas switch was made by venting the chamber over a 5-min period with ~6,000 standard liters of one of the two dive mixtures, holding the depth constant. After the switch, a delay of 4.5 min was allowed for sampling of the chamber atmosphere for gas analysis. Compression to the final depth, up to 50 ATA, was then begun with the dive mixture. Clocking of bottom time, which ranged up to 60 min, started as soon as the final depth was reached. All compression was done at 1.8 ATA/min. The animals were held at that depth for up to 60 min and were then decompressed with varying profiles back to 10.8 ATA. They were then observed for 30 min for signs of DCS, as described previously (18).
Throughout the dive and postdecompression period, the animals were exercised by rotating the cage at a perimeter speed of ~3 m/min to ensure that all animals sustained a similar level of activity and to facilitate DCS scoring. For data analysis, decompression results were recorded as no DCS symptoms, obvious DCS, or death. Therefore, the category DCS included the subset category of death. Two different scorers were involved in these experiments, although only one scorer participated in any one dive. After the 30-min postdecompression period, all surviving animals were killed by flushing the chamber at 10.8 ATA with CO2. The chamber was then decompressed to the surface, and the animals were again weighed.
Three series of dives were performed (details in Appendix).
SATURATION (SAT) DIVES. This series compared the decompression risk of He and H2 while minimizing the confounding issues of gas uptake and washout. All dives were done with a 60-min bottom time. The dive depth was varied to produce a range in incidence levels from 0 to 100% for both DCS and death for each gas. Experience has shown that this wide range in incidence is necessary for effective modeling. Based on prior work (17), the 60-min time at depth should produce saturation for He, although the model used for analysis and described in Data Analysis: the Model does not assume this. All dives were decompressed rapidly (<1 min) to 10.8 ATA to minimize gas washout.
VARIABLE TIME-AT-DEPTH (TD) DIVES. This series examined the rates of gas uptake of He and H2 by allowing a variable amount of time for gas to enter the animal while minimizing gas washout during decompression. Bottom time was varied from 0 (immediate decompression on reaching depth) to 20 min followed by rapid decompression, with the goal again to generate the full range of incidences for both DCS and death.
VARIABLE DECOMPRESSION (VD) DIVES. These dives compared the rates of gas elimination of He and H2 by varying the decompression time primarily via the length and number of stops during ascent rather than via travel rate. The animals were decompressed with a number of different profiles varying from rapid (<1 min) to slow (0.9 or 1.8 ATA/min), with as many as four stops of up to 60 min each.
The three dive series were conducted in sequential order over a period of 3 yr. After preliminary experiments to define the appropriate range in dive profiles for a specific series, the dives were conducted in random order, generally with two or three dives per day. A specific dive profile (i.e., identical depth, time at depth, and decompression) was replicated up to 6 times, resulting in up to 30 rats exposed to the same pressure history. Depth vs. time records of each dive were recorded on a personal computer with the PC-ACQUISITOR data-acquisition system (Dianachart, Rockaway, NJ) to confirm the profile accuracy. Actual depth at any time was generally within 0.05 ATA of the expected value.
When at depth, no venting of the chamber was done to remove CO2 or add O2. Gas (dive mixture) was added only to compensate for any very minor leakage that occurred to maintain depth. Soda lime on a tray below the animal cage was used to absorb CO2. CO2 levels were not measured routinely during the actual experiments. However, previous experience at shallower depths (i.e., 5-8 ATA) indicated that CO2 should be effectively removed this way and kept below 1% surface equivalent. This was confirmed several times for the present dives by drawing samples in gastight syringes from the chamber and analyzing them. During the postdecompression period at 10.8 ATA, the chamber was vented for 20 s with the dive mixture at 5, 15, and 25 min to slow the decline in O2. During the experiments, O2 was observed to fall by up to 0.1% from the starting concentration of 2.0-2.2%, resulting in a lower O2 limit of 1.9%.
At depth, the chamber atmosphere was kept at 30.0 ± 1.5°C by means of a heating-cooling system built into the chamber and regulated by a temperature controller (Omega CN9000A series miniature autotune temperature controller, Omega Engineering, Stamford, CT). During compression, the chamber atmosphere increased by 3-5°C. However, this temperature change was transient, and the atmosphere generally returned to 30°C in <5 min. During the rapid ascent, the temperature dropped to 2-13°C but returned to 30°C in <1 min. During the slow ascent (0.5-1 ATA/min), little deviation from the desired temperature was observed.
The dive profiles used reflect several requirements. For safety reasons, the maximum percentage of O2 in H2 in the chamber atmosphere was limited to 2%. This is well below the flammability limits of 3.5-4% O2 for H2 mixtures reported over a large range of pressures (11, 25). It was also arbitrarily decided to perform the gas switch during compression at the same depth where the animals would be decompressed at the end of the dive. This decompression depth (10.8 ATA) would be the lowest possible pressure while still maintaining normoxia (0.21 ATA O2) at the lower limit of 1.9% O2.
Gas analysis. An automated gas chromatograph (Shimadzu model GC-9A, Shimadzu, Columbia, MD) with thermal conductivity detection and pneumatic sampling valves was used to analyze the chamber atmosphere once every 9 min for He, H2, N2, and O2. Ar was used as the carrier gas to allow analysis of both He and H2 with a molecular sieve 5A packed column (1/8 inch OD by 12 foot length, 60/80 mesh; Supelco, Bellefonte, PA). Current of the thermal conductivity detection was set at 75 mA, and both column and reference gas flows were 50 ml/min. Analysis was done isothermally at 60°C. Peak analysis and quantitation were performed with a Shimadzu CR601 chromatopac integrator based on a one-point calibration with a gravimetric primary standard obtained commercially and certified to ±1% relative to the stated value: 1) 2% O2-2% N2-4% He-balance H2 for H2 dives and 2) 2% O2-2% N2-balance He for He dives. These standards were selected to be very close to the actual composition of the chamber atmosphere to enhance analytic accuracy. Accuracy of analysis was estimated at ±2% relative to both O2 and residual He (for H2 dives) and ±5% relative to residual N2.
Data Analysis: the Model
A dose-response model predicting the probability of DCS in rats was fit to all three series of data by the technique of maximum likelihood (7). Parameter values of the model were adjusted to maximize the log likelihood (LL) of the model with a modified Marquardt nonlinear estimation algorithm (22). The likelihood ratio (LR) test was used to evaluate the significance of parameters based on improvement in "goodness of fit" (15). The shape of the likelihood surface near the converged parameters was used to estimate the precision of the parameter values.All DCS cases were treated equally, with no allowance in the model for grades in severity. The only accommodation for differences in response was to model all DCS cases (including fatalities) and then to repeat the modeling with only cases of death. The dose-response model used for this analysis was the Hill equation
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(1) |
The dose in Eq. 1 represents a measure of decompression stress and was defined in a manner similar to previous reports (17, 18) based on the traditional idea of total gas supersaturation. In the present experiments, the possible gases contributing to the decompression response are He, H2, N2, and O2; CO2 is ignored. To allow for possible differences in gases, each partial pressure is multiplied by a relative potency (RP) value that weights each gas according to risk on a per unit pressure basis. The resulting equation for dose, in ATA, is
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![+ (Pti<SUB>N<SUB>2</SUB></SUB> · RP<SC>n</SC><SUB>2</SUB>)] − 10.8](/content/vol82/issue3/fulltext/892/img003.gif)
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(2) |
The tissue partial pressures of He, H2, and N2 in the animal were obtained with single-exponential kinetics, assuming a single compartment (i.e., whole rat) even though real tissues need a more complex model (12, 23). After a step change in partial pressure of one gas at time 0 (T0), the Pti of the gas at time T can be described by the following equation for T > T0
![Pti = (Pam<SUB><IT>i</IT></SUB> − Pti<SUB>0</SUB>) · [1 − e<SUP>−(<IT>t</IT>−<IT>t</IT><SUB>0</SUB>)/TC<SUB><IT>i</IT></SUB></SUP>] + Pti<SUB>0</SUB>](/content/vol82/issue3/fulltext/892/img004.gif)
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(3) |
The situation becomes more complicated when calculating Pti during actual dives where the ambient gas partial pressures change in a nonstepwise manner (e.g., during compression, gas switching, or decompression). The solution used in the present analysis was to treat each dive as a series of partial pressure ramps that describe the pressure history of the dive. Partial pressures of individual gases at the beginning and ending of each ramp were estimated by multiplying the chamber pressure by the percentage of each gas as measured by gas chromatography. Once 10.8 ATA were reached during compression, O2 was assumed to stay constant at 2.0% for the rest of the dive. For H2 dives, the partial pressure of the residual He after the shift to H2 at 10.8 ATA was calculated at two points: 1) immediately after the gas switch and 2) at the depth just before the start of decompression. In these cases, He pressure was assumed to decline linearly from the time when the depth was first reached to the start of decompression.
For calculation purposes, each ramp was subdivided into a number of smaller time intervals, and Eq. 3 was used to successively compute Pti values at each interval along each ramp until decompression was completed. This procedure was performed for each of the gases that was being considered, in this case He, H2, and N2. Separate TCs for the uptake (TCin) and washout (TCout) of each gas allowed for the possibility of asymmetry in gas kinetics. This was implemented by taking the Pti for each gas and comparing it to the Pami for that gas. When Pti0 > Pami in Eq. 3, the TCin was replaced with the TCout. This situation generally occurred some time after decompression began, although in the case of He washout during a H2 dive, TCout for He was used even while H2 was still washing in.
Gas kinetics in Eq. 3 assume that, at equilibrium, the partial pressures in the animal become equal to those in the chamber. This assumption avoids the difficult task of choosing a more complicated model based on inadequate knowledge of tissue-blood relationships. Because decompression data often do not allow resolution of very different models, simpler models frequently fit the data as well as, or better than, more complex ones. Although Eq. 3 models gas kinetics in the rat, it is important to emphasize that gas uptake and washout were not actually measured. Consequently, what is being modeled is the animal response. The TCs that are being estimated define the rates of change in processes that affect the probability of DCS or death, although interpretation in terms of gas kinetics is made in this report.
The premise behind the definition of dose was that the gas supersaturation existing immediately at the completion of decompression is the measure of insult, leading to the development of DCS. Thus the model estimates the risk of DCS that starts to develop immediately on surfacing and assumes that there is no risk of DCS before this. Problems related to this assumption are discussed below.
The partial pressures of the gases are reported in absolute atmospheres. To estimate the RP values, one of the potencies had to be fixed so that the other potencies could be calculated in relation to it. The RPHe value was arbitrarily set at 1.0 so that the P50 would be expressed in terms of the partial pressure of He in absolute atmospheres. The effect of this weighting calculation was to convert exposures of H2 and N2 into equivalent He exposures.
Because animal weight has a significant effect on the decompression outcome, a weight correction term for dose was included in the model, as previously done, with a power function (17, 18). Animal weight (Wt), normalized to a weight (260 g) close to the average weight of all animals (258 g), was raised to an exponent denoted as the weight factor (WtF). Consequently, the final expression for dose was
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(4) |
The three dive series were initially analyzed separately. Parameter estimation began with the simplest possible model: P50, n, and symmetrical gas kinetics, with a single TC for all inert gases. Each subsequent level of complexity of the model, with all possible combinations of estimated parameters, was evaluated by at least five different sets of starting parameter values to ensure that the maximum LL found was a global and not a local maximum. Parameter combinations that showed promising improvement to the fit were explored with many more starting values so that, overall, several thousand separate starting parameter sets were evaluated.
The next step was to perform an LR test to determine whether the data sets were combinable
![LR = 2 · [LL<SUB>1+2</SUB> − (LL<SUB>1</SUB> + LL<SUB>2</SUB>)]](/content/vol82/issue3/fulltext/892/img006.gif)
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(5) |
In summary, this model 1) predicts the probability of DCS in rats subjected to dives on 2% O2-balance He or 2% O2-balance H2; 2) assumes that the decompression response is dependent on the degree of supersaturation of the gases He, H2, and N2 in the animal; and 3) is used to estimate the parameters governing the location and shape of the dose-response curve, the RP values of the gases, the exponent correcting for animal weight, and the TCin and TCout values of the individual gases.
RESULTS
Table 1 presents a summary of the decompression results from 1,607 dives with the rats that were used for modeling. Detailed results of these data are given in the Appendix. Data include results from all workup dives that were done to define the experimental profiles for each dive series. Overall incidence was 82.0% for DCS and 23.4% for death. The incidence rates were similar for He and H2 dives (83.4 and 79.1%, respectively, for DCS; 24.1 and 22.0%, respectively, for death). Rat weights before diving ranged from 192 to 318 g with a mean of 258 ± 17 (SD) g. The animals experienced a mean drop of 9 ± 3 g by the end of the experiments. Gas-switching effectiveness varied with the specific series, with the postswitch residual He concentration ranging from 1.8 to 4.8% for the Sat series, 5.3 to 10.6% for the TD series, and 11.2 to 13.2% for the VD series. These gas-switch differences among series are thought to reflect plumbing changes that were made to the inside of the chamber over the course of the investigation, which affected the flow of gas during the switching procedure.
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Although the three dive series will be briefly described here, conclusions regarding the decompression differences between He and H2 will be based on the model analysis of the combined data discussed in Model Analysis.
Sat Dives
The DCS and death incidences increased with saturation depth for both He and H2 (Fig. 1). Deeper dives were needed for He compared with H2 to produce similar incidence levels, suggesting a greater H2 potency for causing DCS. For example, H2 dives at depths from 19 to 27 ATA produced DCS incidences from 0 to 100%, whereas He dives required depths from 25 to 37 ATA to span the same range. To produce death, the corresponding depth range was 27-33 ATA for H2 compared with 36-46 ATA for He.
) and H2 (
), both 2%
O2. Shallower dives were needed
for H2 compared with He to produce
similar incidence levels. This reflects greater DCS potency of
H2. Decompression was rapid (<1
min) to 10.8 ATA. Values are experimentally observed incidence values
based on 4-15 animals (see
Appendix). Curves are predictions
from Sat + time-to-depth (TD) dive models (Sat + TD; see Table 2), with
animal weight set at 260 g.
TD Dives
These dives were done at 28-47 ATA for He and 27-33 ATA for H2, again indicating that deeper dives were needed with He than with H2 to produce similar incidence rates. Incidence levels for both gases tended to increase similarly, with increasing bottom time, until a plateau was reached that suggested comparable rates of gas uptake for the two gases (Fig. 2).
) and H2
(), both 2% O2 with saturation
achieved in <15 min. Data and plots for He are for deeper dives than
those for H2 to produce similar
incidence rates, again reflecting greater DCS potency of
H2. Decompression was rapid (<1
min) to 10.8 ATA. Values are experimentally observed incidence values
based on 5-25 animals (see
Appendix). Curves are predictions
from Sat + TD models (see Table 2), with animal weight set at 260 g.
VD Dives
Difficulty was encountered during initial He dives in defining the profiles that produced a low incidence of DCS. To reduce the DCS risk, the decompression time was increased by inserting additional decompression stops, particularly at relatively deep depths. Surprisingly, this approach appeared to have little effect on the incidence of DCS. However, as a result, the majority (84%) of dives in this series were done on He before finishing up with a small number of H2 dives, all at the same depth. In contrast to He, the DCS incidence appeared to decline with an increasing amount of decompression time when using H2.For the VD dives, there were 80 cases where DCS symptoms were observed during ascent before reaching 10.8 ATA. All but three of these dives were on He. For He, 25 of these 77 early cases died; none of the 3 rats showing early symptoms on H2 died. Although these DCS cases violate the assumption that there is no DCS risk until the observation depth is reached, treating these "early" DCS cases as having occurred before arrival at that depth results in censored data. For the purposes of this study, we will consider all animals on a common pressure exposure to have been given the same dose.
The large number of different dive profiles in this series makes it difficult to evaluate how the gas washout rates of the two gases compare without modeling.
Model Analysis
Model parameters were estimated separately for DCS and death with the model described by Eqs. 1-4 (Table 2). Only parameters found to be significant at the 0.05 level are included. Sat and TD dives were found combinable by LR testing. Thus parameters for the combined model (Sat + TD) are given. The VD dives were not combinable with either or both of the other two series; thus the parameters for the VD dives are presented separately.
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Sat + TD. The model allowed for different TCin and TCout values. However, because only rapid decompression procedures were used for Sat + TD, the data did not provide sufficient information on washout to estimate TCout values. Consequently, TCout was set equal to TCin for each gas, so only TCin values are given in Table 2.
VD. Because VD dives had relatively long bottom times, these profiles were not well suited for estimating TCin values. Thus it was not unexpected that TCin values in the VD1 model, which estimated all parameters, were very poorly defined. This model was also accompanied by RPH2 values with very large standard errors. This undoubtedly is partly due to the strong correlation observed between RPH2 and TCout for H2 because the dose can be altered by adjusting either parameter or some combination of the two. Such problems did not occur with the Sat and TD data because the TCin is well determined by the TD data and RPH2 can be estimated, independently of the kinetics, from the Sat data.
To try to improve the model estimates for VD, TCin values were fixed at the values estimated for Sat + TD, and the model was reestimated. This reduced the error in RPH2 and TCout values. This model is denoted VD2. Standard errors for the H2 TCout values were further reduced by refitting the model, again after fixing both RPH2 and TCin at values estimated for Sat + TD. This model is called VD3. In both the VD2 and VD3 models, the parameters P50 and n did not change appreciably from the initial VD1 model in which TCin and RPH2 values had been estimated.
Model VD4 was a test for the significance of asymmetrical kinetics as estimated in VD1-VD3. In this version, the TCout parameters were set equal to the TCin values, resulting in symmetrical gas uptake-washout. This produced much poorer fits as indicated by the LL value, which is ~17 LL worse for both DCS and death in VD4 than in VD3 for the same number of parameters. The symmetrical kinetic TCs estimated in VD4 are intermediate in value between the previously estimated uptake and washout values (VD3). This test (VD4) supports the strong asymmetry estimated in VD1-VD3.
All VD models are included in Table 2. Model VD1 is included to show the changes that occurred going from this model to VD2 and VD3. Models VD2 and VD3 are similar, with the main difference being the greater precision associated with the H2 TCout estimates for VD3.
Parameter Estimates (Models Sat + TD and VD2-VD3)
In comparing the models for DCS and death, the P50 values for death were larger, as would be expected, because a higher dose is required to cause death. The exponent defining the degree of slope of the central portion of the response curve was larger for Sat + TD vs. VD, particularly in the case of death. None of the models required separate exponents for He and H2 or a nonzero potency term for N2. The latter was not surprising because gas switching during compression generally removed all detectable N2 from the chamber atmosphere. Therefore, little information was available to estimate N2 potency.The potency of H2 was estimated at
~10-20% greater than that of He for causing DCS overall and
~30-35% greater than He for death. Predictive response curves
(Fig. 1) illustrate the differences in potency and model agreement with
the Sat data. Uptake rates were unresolvable between the two gases, so
a single TCin value was used that
was estimated at ~2-3 min, leading to saturation in <15 min
(Figs. 2 and 3). Washout of both gases was
over an order of magnitude slower than uptake, with He washout (TC
~1.5-3 h) substantially slower than
H2 washout (TC ~0.5 h; Fig. 3).
This would necessitate a much longer decompression time to avoid DCS when using He. He washout was approximately twice as slow for DCS vs.
death.
For Sat + TD, inclusion of a weight correction (the parameter WtF) in the model produced a significant improvement in fit for both DCS and death. This was not the case for VD.
Effectiveness of the Model
The ability of the models to describe the wide range of dive profiles was examined by plotting the difference between model prediction and observed incidence vs. total decompression time for each different dive profile (Fig. 4). All the data were used in this exercise, with the observed values being the mean incidence rates of the dive profiles. The predictive values were derived from the reported best fit model for Sat + TD for those sets of dives and the model VD3 for those dives. Animal weight was set at 260 g in all model predictions. The scatter of points around zero illustrates that the models predict DCS or death without significant bias and generally equally well regardless of total decompression time.
DISCUSSION
This investigation supported the initial hypothesis that there are differences in the risk of DCS between He and H2 and demonstrated differences between He and H2 in both potency for causing DCS and in the estimated washout rate in the whole rat. Here, potency defines the level of risk based on the estimated Pti values of the gases. Exchange rates (gas uptake or washout) govern the rate of change in the Pti values of the gases with time. Gas kinetics were extrapolated from rate constants estimated from the changes in DCS risk rather than determined from the direct measurement of gas uptake and washout. Both potency and rate constants interact to affect the degree of risk associated with a specific dive profile.
Previous work has suggested that the greater potency of "riskier" gases may be due to larger volumes of gas evolving during decompression (20). These gas volumes would be expected to be affected by differences among gases in tissue solubility and/or diffusivity and in rates of bubble development. With the use of published data on gas properties, some simple comparisons can be made, although it should be emphasized that it is unknown how well such data relate to actual tissues under pressure. Coefficients for H2 and He solubility in water at 37°C (0.0185 and 0.0099 ml gas/ml fluid, respectively; Ref. 24) are in the relative proportion of 1.9 for H2-to-He. A similar ratio for the H2-to-He solubility in oil (0.0495 and 0.0168 ml gas/ml fluid, respectively; Ref. 24) is 2.9. These solubility ratios are considerably higher than the observed potency differences (i.e., up to 35% or a ratio of 1.35), although this was also the case when He, N2, and Ar were similarly compared previously (20). However, the greater solubility of H2 in both water and oil would support the greater potential gas volume-greater risk hypothesis.
The rates of gas exchange of animals or humans are also believed to depend on solubility and diffusivity properties as well as on the partial pressure gradients and on factors such as the relative importance of gaseous diffusion and blood perfusion. In examining the rate constants estimated here, several observations are particularly interesting in light of previous work with rats at depths up to 9 ATA (17-19). First, at the shallower depths, the rate of gas uptake was similar to that of gas washout for both N2 (17, 19) and He (R. S. Lillo, unpublished data). However, N2 was approximately three times slower than He in both cases. This is in contrast to the much slower (over an order of magnitude) washout compared with uptake seen here at the greater depths for He and H2. Second, although the uptake rates reported here for He and H2 are indistinguishable and similar to those found before for He (17), the washout rates for these two gases during decompression are very different.
Despite previous reports of reduced rates of inert gas elimination during decompression due to cardiovascular changes or bubble development (5, 10), the magnitude of slowing estimated here was unexpected. This suggests the possibility that the increased depth of the present dives may be affecting washout. Another explanation may be that the risk of DCS becomes uncoupled from the gas load in the animal at greater depths, so that risk remains elevated long after most excess gas has been eliminated. A recent examination of the time course of predicted bubble evolution with predicted DCS risk in humans has suggested that gas-phase dynamics may not fully explain persistent DCS risk (1).
These experiments do not specifically model a type of human DCS. Rather, we take a simplistic approach with these dives in terms of gas loading and elimination and how these processes relate to DCS. In this way, we avoid having to make assumptions regarding the etiology of DCS that is not well understood and is probably very complex and varies depending on the tissues involved. Whether these findings relating to a very severe type of DCS have an application to DCS in humans is unknown. Obviously, the scaling effect going from a rat to a human would prevent use of absolute gas rate constants (3, 16). Thus it is unknown whether the decompression advantage of the faster washout of H2 or the disadvantage of its increased potency, observed in the rat, would be important for human diving. However, these findings raise the possibility of exploiting such differences between He and H2 to manipulate the DCS risk after saturation diving with humans.
ACKNOWLEDGEMENTS
This work was supported by Naval Medical Research and Development Command Work Unit No. 62233N MM33P30.004-1057.
FOOTNOTES
Address for reprint requests: R. S. Lillo, Code 0541, Diving and Environmental Physiology Dept., Naval Medical Research Institute, 8901 Wisconsin Ave., Bethesda, MD 20889-5607.
Received 26 June 1996; accepted in final form 5 November 1996.
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