Bubbles Quantified In vivo by Ultrasound Relates to Amount of Gas Detected Post-mortem in Rabbits Decompressed from High Pressure.

The pathophysiological mechanism of decompression sickness is not fully understood but there is evidence that it can be caused by intravascular and autochthonous bubbles. Doppler ultrasound at a given circulatory location is used to detect and quantify the presence of intravascular gas bubbles as an indicator of decompression stress. In this manuscript we studied the relationship between presence and quantity of gas bubbles by echosonography of the pulmonary artery of anesthetized, air-breathing New Zealand White rabbits that were compressed and decompressed. Mortality rate, presence, quantity, and distribution of gas bubbles elsewhere in the body was examined postmortem. We found a strong positive relationship between high ultrasound bubble grades in the pulmonary artery, sudden death, and high amount of intra and extra vascular gas bubbles widespread throughout the entire organism. In contrast, animals with lower bubble grades survived for 1 h after decompression until sacrificed, and showed no gas bubbles during dissection.

Differentiation at necropsy between in vivo gas embolism and putrefaction using a gas score.

Gas bubble lesions consistent with decompression sickness in marine mammals were described for the first time in beaked whales stranded in temporal and spatial association with military exercises. Putrefaction gas is a post-mortem artifact, which hinders the interpretation of gas found at necropsy. Gas analyses have been proven to help differentiating putrefaction gases from gases formed after hyperbaric exposures. Unfortunately, chemical analysis cannot always be performed. Post-mortem computed tomography is used to study gas collections, but many different logistical obstacles and obvious challenges, like the size of the animal or the transport of the animal from the stranding location to the scanner, limit its use in stranded marine mammals. In this study, we tested the diagnostic value of an index-based method for characterizing the amount and topography of gas found grossly during necropsies. For this purpose, putrefaction gases, intravenously infused atmospheric air, and gases produced by decompression were evaluated at necropsy with increased post-mortem time in New Zealand White Rabbits using a gas score index. Statistical differences (P<0.001) were found between the three experimental models immediately after death. Differences in gas score between in vivo gas embolism and putrefaction gases were found significant (P<0.05) throughout the 67h post-mortem. The gas score-index is a new and simple method that can be used by all stranding networks, which has been shown through this study to be a valid diagnostic tool to distinguish between fatal decompression, iatrogenic air embolism and putrefaction gases at autopsies.

A CT-, PET- and MR-imaging-compatible hyperbaric pressure chamber for baromedical research.

OBJECTIVES: We describe the development of a novel preclinical rodent-sized pressure chamber system compatible with computed tomography (CT), positron emission tomography (PET) and magnetic resonance imaging (MRI) that allows continuous uncompromised and minimally invasive data acquisition throughout hyperbaric exposures. The effect of various pressures on the acquired image intensity obtained with different CT, PET and MRI phantoms are characterised. MATERIAL AND METHODS: Tissue-representative phantom models were examined with CT, PET or MRI at normobaric pressure and hyperbaric pressures up to 1.013 mPa. The relationships between the acquired image signals and pressure were evaluated by linear regression analysis for each phantom. RESULTS: CT and PET showed no effect of pressure per se, except for CT of air, demonstrating an increase in Hounsfield units in proportion to the pressure. For MRI, pressurisation induced no effect on the longitudinal relaxation rate (R1), whereas the transversal relaxation rate (R2) changed slightly. The R2 data further revealed an association between pressure and the concentration of the paramagnetic nuclei gadolinium, the contrast agent used to mimic different tissues in the MRI phantoms. CONCLUSION: This study demonstrates a pressure chamber system compatible with CT, PET and MRI. We found that no correction in image intensity was required with pressurisation up to 1.013 mPa for any imaging modality. CT, PET or MRI can be used to obtain anatomical and physiological information from pressurised model animals in this chamber.

Career perspective: Alf O. Brubakk-looking back to see ahead.

The following describes my professional life up till today, but it also describes what I think lies ahead. I have led an interesting professional life and been lucky enough to be at the centre of some of the important development in modern medicine and diving, namely ultrasound in cardiology and the mechanisms of decompression. I therefore should be able to see some of the most challenging and exciting problems ahead. Ultrasound in cardiology has developed from simply listening to the Doppler signal to determine the velocity of blood flow to the complicated description of images presented today. Diving, in addition to being an important commercial and environmental activity, exposes the individual to intermittent hyperoxia and pressure reductions. These challenges evoke the production of radical oxygen species (ROS) and microparticles (MP) that also are central to many pathophysiologic mechanisms that are involved in a number of severe human diseases. Thus, diving can be regarded as an important model of disease and allows us to study their effects on healthy young individuals. The future thus points towards an integration of environmental physiology with detailed physiological and pathophysiological mechanisms and makes diving physiology a potentially very important field of study.

Saturation diving; physiology and pathophysiology.

In saturation diving, divers stay under pressure until most of their tissues are saturated with breathing gas. Divers spend a long time in isolation exposed to increased partial pressure of oxygen, potentially toxic gases, bacteria, and bubble formation during decompression combined with shift work and long periods of relative inactivity. Hyperoxia may lead to the production of reactive oxygen species (ROS) that interact with cell structures, causing damage to proteins, lipids, and nucleic acid. Vascular gas-bubble formation and hyperoxia may lead to dysfunction of the endothelium. The antioxidant status of the diver is an important mechanism in the protection against injury and is influenced both by diet and genetic factors. The factors mentioned above may lead to production of heat shock proteins (HSP) that also may have a negative effect on endothelial function. On the other hand, there is a great deal of evidence that HSPs may also have a "conditioning" effect, thus protecting against injury. As people age, their ability to produce antioxidants decreases. We do not currently know the capacity for antioxidant defense, but it is reasonable to assume that it has a limit. Many studies have linked ROS to disease states such as cancer, insulin resistance, diabetes mellitus, cardiovascular diseases, and atherosclerosis as well as to old age. However, ROS are also involved in a number of protective mechanisms, for instance immune defense, antibacterial action, vascular tone, and signal transduction. Low-grade oxidative stress can increase antioxidant production. While under pressure, divers change depth frequently. After such changes and at the end of the dive, divers must follow procedures to decompress safely. Decompression sickness (DCS) used to be one of the major causes of injury in saturation diving. Improved decompression procedures have significantly reduced the number of reported incidents; however, data indicate considerable underreporting of injuries. Furthermore, divers who are required to return to the surface quickly are under higher risk of serious injury as no adequate decompression procedures for such situations are available. Decompression also leads to the production of endothelial microparticles that may reduce endothelial function. As good endothelial function is a documented indicator of health that can be influenced by regular exercise, regular physical exercise is recommended for saturation divers. Nowadays, saturation diving is a reasonably safe and well controlled method for working under water. Until now, no long-term impact on health due to diving has been documented. However, we still have limited knowledge about the pathophysiologic mechanisms involved. In particular we know little about the effect of long exposure to hyperoxia and microparticles on the endothelium.

Ultrasound detection of vascular decompression bubbles: the influence of new technology and considerations on bubble load.

INTRODUCTION: Diving often causes the formation of 'silent' bubbles upon decompression. If the bubble load is high, then the risk of decompression sickness (DCS) and the number of bubbles that could cross to the arterial circulation via a pulmonary shunt or patent foramen ovale increase. Bubbles can be monitored aurally, with Doppler ultrasound, or visually, with two dimensional (2D) ultrasound imaging. Doppler grades and imaging grades can be compared with good agreement. Early 2D imaging units did not provide such comprehensive observations as Doppler, but advances in technology have allowed development of improved, portable, relatively inexpensive units. Most now employ harmonic technology; it was suggested that this could allow previously undetectable bubbles to be observed. METHODS: This paper provides a review of current methods of bubble measurement and how new technology may be changing our perceptions of the potential relationship of these measurements to decompression illness. Secondly, 69 paired ultrasound images were made using conventional 2D ultrasound imaging and harmonic imaging. Images were graded on the Eftedal-Brubakk (EB) scale and the percentage agreement of the images calculated. The distribution of mismatched grades was analysed. RESULTS: Fifty-four of the 69 paired images had matching grades. There was no significant difference in the distribution of high or low EB grades for the mismatched pairs. CONCLUSIONS: Given the good level of agreement between pairs observed, it seems unlikely that harmonic technology is responsible for any perceived increase in observed bubble loads, but it is probable that our increasing use of 2D ultrasound to assess dive profiles is changing our perception of 'normal' venous and arterial bubble loads. Methods to accurately investigate the load and size of bubbles developed will be helpful in the future in determining DCS risk.

Acute and potentially persistent effects of scuba diving on the blood transcriptome of experienced divers.

During scuba diving, the circulatory system is stressed by an elevated partial pressure of oxygen while the diver is submerged and by decompression-induced gas bubbles on ascent to the surface. This diving-induced stress may trigger decompression illness, but the majority of dives are asymptomatic. In this study we have mapped divers' blood transcriptomes with the aim of identifying genes, biological pathways, and cell types perturbed by the physiological stress in asymptomatic scuba diving. Ten experienced divers abstained from diving for >2 wk before performing a 3-day series of daily dives to 18 m depth for 47 min while breathing compressed air. Blood for microarray analysis was collected before and immediately after the first and last dives, and 10 matched nondivers provided controls for predive stationary transcriptomes. MetaCore GeneGo analysis of the predive samples identified stationary upregulation of genes associated with apoptosis, inflammation, and innate immune responses in the divers, most significantly involving genes in the TNFR1 pathway of caspase-dependent apoptosis, HSP60/HSP70 signaling via TLR4, and NF-κB-mediated transcription. Diving caused pronounced shifts in transcription patterns characteristic of specific leukocytes, with downregulation of genes expressed by CD8+ T lymphocytes and NK cells and upregulation of genes expressed by neutrophils, monocytes, and macrophages. Antioxidant genes were upregulated. Similar transient responses were observed after the first and last dive. The results indicate that sublethal oxidative stress elicits the myeloid innate immune system in scuba diving and that extensive diving may cause persistent change in pathways controlling apoptosis, inflammation, and innate immune responses.

Sidenafil pre-treatment promotes decompression sickness in rats.

Vascular bubble formation after decompression contributes to endothelial injuries which form the basis for the development of decompression sickness (DCS). Nitric oxide (NO) is a powerful vasodilator that contributes to vessel homeostasis. It has been shown that NO-releasing agent may reduce bubble formation and prevent serious decompression sickness. The use of sildenafil, a well-known, phosphodiesterase-5 blocker, which act by potentiating the vasodilatory effect on smooth muscle relaxation, has never been studied in DCS. The purpose of the present study was to evaluate the clinical effects of sildenafil pre-treatment on DCS in a rat model. 67 rats were subjected to a simulated dive at 90 msw for 45 min before staged decompression. The experimental group received 10 mg/kg of sildenafil one hour before exposure (n = 35) while controls were not treated (n = 32). Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and the level of circulating bubbles in the right cavities was quantified. There were significantly more manifestations of DCS in the sildenafil group than in the controls (34.3% vs 6.25%, respectively, p = 0.012). Platelet count was more reduced in treated rats than in controls (-21.7% vs -7%, respectively, p = 0.029), whereas bubble grades did not differ between groups. We concluded that pre-treatment with sildenafil promotes the onset and severity of neurological DCS. When considering the use of phosphodiesterase-5 blockers in the context of diving, careful discussion with physician should be recommended.

Differentiation at autopsy between in vivo gas embolism and putrefaction using gas composition analysis.

Gas embolism can arise from different causes (iatrogenic accidents, criminal interventions, or diving related accidents). Gas analyses have been shown to be a valid technique to differentiate between putrefaction gases and gas embolism. In this study, we performed systematic necropsies at different postmortem times in three experimental New Zealand White Rabbits models: control or putrefaction, infused air embolism, and compression/decompression. The purpose of this study was to look for qualitative and quantitative differences among groups and to observe how putrefaction gases mask in vivo gas embolism. We found that the infused air embolism and compression/decompression models had a similar gas composition prior to 27-h postmortem, being typically composed of around 70-80 % of N(2) and 20-30 % of CO(2), although unexpected higher CO(2) concentrations were found in some decompressed animals, putting in question the role of CO(2) in decompression. All these samples were statistically and significantly different from more decomposed samples. Gas composition of samples from more decomposed animals and from the putrefaction model presented hydrogen, which was therefore considered as a putrefaction marker.

Simulated dive in rats lead to acute changes in cerebral blood flow on MRI, but no cerebral injuries to grey or white matter.

In this study, the effect of a simulated dive on rat brain was investigated using several magnetic resonance imaging (MRI)-methods and immunohistochemistry. Rats were randomly assigned to a dive- or a control group. The dive group was exposed to a simulated air dive to 600 kPa for 45 min. Pulmonary artery was monitored for vascular gas bubbles by ultrasound. MRI was performed 1 h after decompression and at one and 2 weeks after the dive with a different combination of MRI sequences at each time point. Two weeks after decompression, rats were sacrificed and brains were prepared for histology. Dived rats had a different time-curve for the dynamic contrast-enhanced MRI signal than controls with higher relative signal intensity, a tendency towards longer time to peak and a larger area under the curve for the whole brain on the acute MRI scan. On MRI, 1 and 2 weeks after dive, T2-maps showed no signal abnormalities or morphological changes. However, region of interest based measurements of T2 showed higher T2 in the brain stem among decompressed animals than controls after one and 2 weeks. Microscopical examination including immunohistochemistry did not reveal apparent structural or cellular injuries in any part of the rat brains. These observations indicate that severe decompression does not seem to cause any structural or cellular injury to the brain tissue of the rat, but may cause circulatory changes in the brain perfusion in the acute phase.

Exercise-induced myofibrillar disruption with sarcolemmal integrity prior to simulated diving has no effect on vascular bubble formation in rats.

Decompression sickness is initiated by gas bubbles formed during decompression, and it has been generally accepted that exercise before decompression causes increased bubble formation. There are indications that exercise-induced muscle injury seems to be involved. Trauma-induced skeletal muscle injury and vigorous exercise that could theoretically injure muscle tissues before decompression have each been shown to result in profuse bubble formation. Based on these findings, we hypothesized that exercise-induced skeletal muscle injury prior to decompression from diving would cause increase of vascular bubbles and lower survival rates after decompression. In this study, we examined muscle injury caused by eccentric exercise in rats prior to simulated diving and we observed the resulting bubble formation. Female Sprague-Dawley rats (n = 42) ran downhill (-16º) for 100 min on a treadmill followed by 90 min rest before a 50-min simulated saturation dive (709 kPa) in a pressure chamber. Muscle injury was evaluated by immunohistochemistry and qPCR, and vascular bubbles after diving were detected by ultrasonic imaging. The exercise protocol resulted in increased mRNA expression of markers of muscle injury; αB-crystallin, NF-κB, and TNF-α, and myofibrillar disruption with preserved sarcolemmal integrity. Despite evident myofibrillar disruption after eccentric exercise, no differences in bubble amounts or survival rates were observed in the exercised animals as compared to non-exercised animals after diving, a novel finding that may be applicable to humans.

Effects of hyperbaric oxygen preconditioning on cardiac stress markers after simulated diving.

Hyperbaric oxygen preconditioning (HBO-PC) can protect the heart from injury during subsequent ischemia. The presence of high loads of venous gas emboli (VGE) induced by a rapid ambient pressure reduction on ascent from diving may cause ischemia and acute heart failure. The aim of this study was to investigate the effect of diving-induced VGE formation on cardiac stress marker levels and the cardioprotective effect of HBO-PC. To induce high loads of VGE, 63 female Sprague-Dawley rats were subjected to a rapid ambient pressure reduction from a simulated saturation dive (50 min at 709 kPa) in a pressure chamber. VGE loads were measured for 60 min in anesthetized animals by the use of ultrasonography. The animals were divided into five groups. Three groups were exposed to either diving or to HBO-PC (100% oxygen, 38 min at 303 kPa) with a 45 or 180 min interval between HBO-PC and diving. Two additional groups were used as baseline controls for the measurements; one group was exposed to equal handling except for HBO-PC and diving, and the other group was completely unexposed. Diving caused high loads of VGE, as well as elevated levels of the cardiac stress markers, cardiac troponin T (cTnT), natriuretic peptide precursor B (Nppb), and αB-crystallin, in blood and cardiac tissue. There were strong positive correlations between VGE loads and stress marker levels after diving, and HBO-PC appeared to have a cardioprotective effect, as indicated by the lower levels of stress marker expression after diving-induced VGE formation.

Early genetic responses in rat vascular tissue after simulated diving.

Diving causes a transient reduction of vascular function, but the mechanisms behind this are largely unknown. The aim of this study was therefore to analyze genetic reactions that may be involved in acute changes of vascular function in divers. Rats were exposed to 709 kPa of hyperbaric air (149 kPa Po(2)) for 50 min followed by postdive monitoring of vascular bubble formation and full genome microarray analysis of the aorta from diving rats (n = 8) and unexposed controls (n = 9). Upregulation of 23 genes was observed 1 h after simulated diving. The differential gene expression was characteristic of cellular responses to oxidative stress, with functions of upregulated genes including activation and fine-tuning of stress-responsive transcription, cytokine/cytokine receptor signaling, molecular chaperoning, and coagulation. By qRT-PCR, we verified increased transcription of neuron-derived orphan receptor-1 (Nr4a3), plasminogen activator inhibitor 1 (Serpine1), cytokine TWEAK receptor FN14 (Tnfrsf12a), transcription factor class E basic helix-loop-helix protein 40 (Bhlhe40), and adrenomedullin (Adm). Hypoxia-inducible transcription factor HIF1 subunit HIF1-α was stabilized in the aorta 1 h after diving, and after 4 h there was a fivefold increase in total protein levels of the procoagulant plasminogen activator inhibitor 1 (PAI1) in blood plasma from diving rats. The study did not have sufficient power for individual assessment of effects of hyperoxia and decompression-induced bubbles on postdive gene expression. However, differential gene expression in rats without venous bubbles was similar to that of all the diving rats, indicating that elevated Po(2) instigated the observed genetic reactions.

Concentration of circulating autoantibodies against HSP 60 is lowered through diving when compared to non-diving rats.

OBJECTIVE: Skin and ear infections, primarily caused by Pseudomonas aeruginosa (P. aeruginosa), are recurrent problems for saturation divers, whereas infections caused by P. aeruginosa are seldom observed in healthy people outside saturation chambers. Cystic fibrosis (CF) patients suffer from pulmonary infections by P. aeruginosa, and it has been demonstrated that CF patients have high levels of autoantibodies against Heat shock protein 60 (HSP60) compared to controls, probably due to cross-reacting antibodies induced by P. aeruginosa. The present study investigated whether rats immunised with P. aeruginosa produced autoantibodies against their own HSP60 and whether diving influenced the level of circulating anti-HSP60 antibodies. METHODS: A total of 24 rats were randomly assigned to one of three groups ('immunised', 'dived' and 'immunised and dived'). The rats in group 1 and 3 were immunised with the bacteria P. aeruginosa, every other week. Groups 2 and 3 were exposed to simulated air dives to 400 kPa (4 ata) with 45 min bottom time, every week for 7 weeks. Immediately after surfacing, the rats were anaesthetised and blood was collected from the saphenous vein. The amount of anti-HSP60 rat antibodies in the serum was analysed by enzyme linked immunosorbent assay. RESULTS: The immunised rats (group 1) showed a significant increase in the level of autoantibodies against HSP60, whereas no autoantibodies were detected in the dived rats (group 2). The rats both immunised and dived (group 3) show no significant increase in circulating autoantibodies against HSP60. A possible explanation may be that HSP60 is expressed during diving and that cross-reacting antibodies are bound.

Observation of increased venous gas emboli after wet dives compared to dry dives.

INTRODUCTION: Testing of decompression procedures has been performed both in the dry and during immersion, assuming that the results can be directly compared. To test this, the aim of the present paper was to compare the number of venous gas bubbles observed following a short, deep and a shallow, long air dive performed dry in a hyperbaric chamber and following actual dives in open water. METHODS: Fourteen experienced male divers participated in the study; seven performed dry and wet dives to 24 metres' sea water (msw) for 70 minutes; seven divers performed dry and wet dives to 54 msw for 20 minutes. Decompression followed a Bühlmann decompression procedure. Immediately following the dive, pulmonary artery bubble formation was monitored for two hours. The results were graded according to the method of Eftedal and Brubakk. RESULTS: All divers completed the dive protocol, none of them showed any signs of decompression sickness. During the observation period, following the shallow dives, the bubbles increased from 0.1 bubbles per cm ² after the dry dive to 1.4 bubbles per cm ² after the wet dive. Following the deep dives, the bubbles increased from 0.1 bubbles per cm ² in the dry dive to 2.4 bubbles per cm ² in the wet dive. Both results are highly significant (P = 0.0001 or less). CONCLUSIONS: The study has shown that diving in water produces significantly more gas bubble formation than dry diving. The number of venous gas bubbles observed after decompression in water according to a rather conservative procedure, indicates that accepted standard decompression procedures nevertheless induce considerable decompression stress. We suggest that decompression procedures should aim at keeping venous bubble formation as low as possible.

Venous and arterial bubbles at rest after no-decompression air dives.

PURPOSE: During SCUBA diving, breathing at increased pressure leads to a greater tissue gas uptake. During ascent, tissues may become supersaturated, and the gas is released in the form of bubbles that typically occur on the venous side of circulation. These venous gas emboli (VGE) are usually eliminated as they pass through the lungs, although their occasional presence in systemic circulation (arterialization) has been reported and it was assumed to be the main cause of the decompression sickness. The aims of the present study were to assess the appearance of VGE after air dives where no stops in coming to the surface are required and to assess their potential occurrence and frequency in the systemic circulation. METHODS: Twelve male divers performed six dives with 3 d of rest between them following standard no-decompression dive procedures: 18/60, 18/70, 24/30, 24/40, 33/15, and 33/20 (the first value indicates depth in meters of sea water and the second value indicates bottom time in minutes). VGE monitoring was performed ultrasonographically every 20 min for 120 min after surfacing. RESULTS: Diving profiles used in this study produced unexpectedly high amounts of gas bubbles, with most dives resulting in grade 4 (55/69 dives) on the bubble scale of 0-5 (no to maximal bubbles). Arterializations of gas bubbles were found in 5 (41.7%) of 12 divers and after 11 (16%) of 69 dives. These VGE crossovers were only observed when a large amount of bubbles was concomitantly present in the right valve of the heart. CONCLUSIONS: Our findings indicate high amounts of gas bubbles produced after no-decompression air dives based on standardized diving protocols. High bubble loads were frequently associated with the crossover of VGE to the systemic circulation. Despite these findings, no acute decompression-related pathology was detected.

Immersion before dry simulated dive reduces cardiomyocyte function and increases mortality after decompression.

Diving and decompression performed under immersed conditions have been shown to reduce cardiac function. The mechanisms for these changes are not known. The effect of immersion before a simulated hyperbaric dive on cardiomyocyte function was studied. Twenty-three rats were assigned to four groups: control, 1 h thermoneutral immersion, dry dive, and 1 h thermoneutral immersion before a dive (preimmersion dive). Rats exposed to a dive were compressed to 700 kPa, maintained for 45 min breathing air, and decompressed linearly to the surface at a rate of 50 kPa/min. Postdive, the animals were anesthetized and the right ventricle insonated for bubble detection using ultrasound. Isolation of cardiomyocytes from the left ventricle was performed and studied using an inverted fluorescence microscope with video-based sarcomere spacing. Compared with a dry dive, preimmersion dive significantly increased bubble production and decreased the survival time (bubble grade 1 vs. 5, and survival time 60 vs. 17 min, respectively). Preimmersion dive lead to 18% decreased cardiomyocyte shortening, 20% slower diastolic relengthening, and 22% higher calcium amplitudes compared with controls. The protein levels of the sarco-endoplasmic reticulum calcium ATPase (SERCA2a), Na+/Ca2+ exchanger (NCX), and phospholamban phosphorylation in the left ventricular tissue were significantly reduced after both dry and preimmersion dive compared with control and immersed animals. The data suggest that immersion before a dive results in impaired cardiomyocyte and Ca2+ handling and may be a cellular explanation to reduced cardiac function observed in humans after a dive.

Use of heart rate monitoring for an individualized and time-variant decompression model.

Individual differences, physiological pre-conditions and in-dive conditions like workload and body temperature have been known to influence bubble formation and risk of decompression sickness in diving. Despite this fact, such effects are currently omitted from the decompression algorithms and tables that are aiding the divers. There is an apparent need to expand the modeling beyond depth and time to increase safety and efficiency of diving. The present paper outlines a mathematical model for how heart rate monitoring in combination with individual parameters can be used to obtain a customized and time-variant decompression model. We suggest that this can cover some of the individual differences and dive conditions that are affecting bubble formation. The model is demonstrated in combination with the previously published Copernicus decompression model, and is suitable for implementation in dive computers and post dive simulation software for more accurate risk analysis.

Parameter estimation of the copernicus decompression model with venous gas emboli in human divers.

Decompression Sickness (DCS) may occur when divers decompress from a hyperbaric environment. To prevent this, decompression procedures are used to get safely back to the surface. The models whose procedures are calculated from, are traditionally validated using clinical symptoms as an endpoint. However, DCS is an uncommon phenomenon and the wide variation in individual response to decompression stress is poorly understood. And generally, using clinical examination alone for validation is disadvantageous from a modeling perspective. Currently, the only objective and quantitative measure of decompression stress is Venous Gas Emboli (VGE), measured by either ultrasonic imaging or Doppler. VGE has been shown to be statistically correlated with DCS, and is now widely used in science to evaluate decompression stress from a dive. Until recently no mathematical model has existed to predict VGE from a dive, which motivated the development of the Copernicus model. The present article compiles a selection experimental dives and field data containing computer recorded depth profiles associated with ultrasound measurements of VGE. It describes a parameter estimation problem to fit the model with these data. A total of 185 square bounce dives from DCIEM, Canada, 188 recreational dives with a mix of single, repetitive and multi-day exposures from DAN USA and 84 experimentally designed decompression dives from Split Croatia were used, giving a total of 457 dives. Five selected parameters in the Copernicus bubble model were assigned for estimation and a non-linear optimization problem was formalized with a weighted least square cost function. A bias factor to the DCIEM chamber dives was also included. A Quasi-Newton algorithm (BFGS) from the TOMLAB numerical package solved the problem which was proved to be convex. With the parameter set presented in this article, Copernicus can be implemented in any programming language to estimate VGE from an air dive.

S100B and its relation to intravascular bubbles following decompression.

INTRODUCTION: When neurological damage occurs in divers, it is considered to be caused by gas bubbles. Entrapment of these bubbles may lead to cellular injury and cerebral oedema. S100B is a protein biomarker that is released in CNS injuries and the concentration is related to the amount of brain damage. METHODS: A total of 27 rats were randomly assigned to one of three groups. Group I served as controls (n = 9). Group II (n = 7) underwent a simulated dive to 400 kPa and Group III to 700 kPa (n = 11). In groups II and III, venous gas bubble scores were evaluated by ultrasound during the first hour after surfacing. The amount of S100B in serum after the dives was tested using a commercial ELISA kit. Bubble grades were compared to S100B protein concentrations. RESULTS: The average level of S100B was significantly higher in rats compressed to 700 kPa compared to the control rats, (P = 0.038) and the rats compressed to 400 kPa, (P = 0.003). There was no difference in S100B concentration between groups I and II. Following the dive to 700 kPa, there were significantly higher bubble grades observed than following the dive to 400 kPa (P = 0.001). CONCLUSION: The correlation between bubble grade and an increase in serum protein level of S100B indicates that this protein may be useful as a biomarker for neurological damage caused by decompression.