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.     

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.     

On the likelihood of decompression sickness

The occurrence of decompression sickness in animals and humans is characterized by the extreme variability of individual response. Nevertheless, models and analyses of decompression results have generally used a critical value approach to separate safe and unsafe decompression procedures. Application of the principle of maximum likelihood provides a formal and consistent way to quantify decompression risk and to apply models to data on decompression outcome. By use of the maximum likelihood principle, a number of models were fit to data from dose-response and maximum pressure-reduction experiments with both rats and men. Several different formulations of two- and three-parameter models described the data well. In addition to summarizing data sets, the analyses provide a way to maximize the value of experimental observations, test theoretical predictions, estimate uncertainty in conclusions, and recommend safe practices.     

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.     

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.     

Consumption of platelets in decompression sickness of rabbits

Platelet behavior was studied in rabbit decompression sickness which was brought about by the exposure to 6 ATA for 40 min (bottom time) followed by rapid decompression. Platelet counts significantly decreased after the decompression. Kinetic studies with 111In-oxine-labeled platelets revealed shortened survivals of circulating platelets, and audioradiograms indicated the accumulation of radioactivity in the lungs after the decompression. Although there was no change in the mode volume of platelets after the decompression, the transient appearance of circulating smaller or fragmented platelets suggested a random overdestruction of platelets. Whole and releasable adenine nucleotide contents of platelets were decreased significantly after the decompression. There were no significant changes in cytoplasmic adenine nucleotide contents. Therefore, in decompression sickness, the circulating platelets behaved similarly to those in acquired storage pool disease. Platelet thrombi were found in the pulmonary arteries, compatible with the accumulation of 111In-oxine-labeled platelets. These findings suggest that circulating air bubbles interact with platelets, causing the platelet release reaction, and these activated platelets participate in the formation of thrombi in experimental decompression sickness.     

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.     

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.     

Neuroprotective role of the TREK-1 channel in decompression sickness

Nitrogen supersaturation and bubble formation can occur in the vascular system after diving, leading to death and nervous disorders from decompression sickness (DCS). Bubbles alter the vascular endothelium, activate platelets, and lead to focal ischemia with neurological damage mediated by the mechanosensitive TREK-1 neuronal potassium ion channel that sets pre- and postsynaptic resting membrane potentials. We report a neuroprotective effect associated with TREK-1. C57Bl6 mice were subjected to decompression from a simulated 90 msw dive. Of 143 mice that were wild type (WT) for TREK-1, 51.7% showed no DCS, 27.3% failed a grip test, and 21.0% died. Of 88 TREK-1 knockouts (KO), 26.1% showed no DCS, 42.0% failed a grip test, and 31.8% died. Mice that did not express TREK-1 had lower DCS resistance and were more likely to develop neurological symptoms. We conclude that the TREK-1 potassium channel was neuroprotective for DCS.     

Modeling the dynamics of risk of altitude decompression sickness

A probabilistic model of decompression sickness is modified by introducing corrections that determine more precisely the risk of tissue injury by gas bubbles as a function of blood supply and bubble nucleation intensity. Parameters of the “worst” virtual tissues and theoretical curves corresponding to empirical data on the cumulative probability of decompression sickness symptoms for some altitude decompression procedures are determined. The parameters are shown to depend on final pressure, physical load, and duration of preoxygenation.