Effect of in-water recompression with oxygen to 6 msw versus normobaric oxygen breathing on bubble formation in divers

It is generally accepted that the incidence of decompression sickness (DCS) from hyperbaric exposures is low when few or no bubbles are present in the circulation. To date, no data are available on the influence of in-water oxygen breathing on bubble formation following a provocative dive in man. The purpose of this study was to compare the effect of post-dive hyperbaric versus normobaric oxygen breathing (NOB) on venous circulating bubbles. Nineteen divers carried out open-sea field air dives at 30 msw depth for 30 min followed by a 9 min stop at 3 msw. Each diver performed three dives: one control dive, and two dives followed by 30 min of hyperbaric oxygen breathing (HOB) or NOB; both HOB and NOB started 10 min after surfacing. For HOB, divers were recompressed in-water to 6 msw at rest, whereas NOB was performed in a dry room in supine position. Decompression bubbles were examined by a precordial pulsed Doppler. Bubble count was significantly lower for post-dive NOB than for control dives. HOB dramatically suppressed circulating bubble formation with a bubble count significantly lower than for NOB or controls. In-water recompression with oxygen to 6 msw is more effective in removing gas bubbles than NOB. This treatment could be used in situations of “interrupted” or “omitted” decompression, where a diver returns to the water in order to complete decompression prior to the onset of symptoms. Further investigations are needed before to recommend this protocol as an emergency treatment for DCS.     

Tissue oxygenation measured with near-infrared spectroscopy during normobaric and hyperbaric oxygen breathing in healthy subjects

To evaluate the possibility of using near-infrared spectroscopy (NIRS) to measure tissue oxygenation (StO₂) during hyperbaric oxygen (HBO) therapy. Nine healthy volunteers (1 female) age 25−37 years, breathed air or oxygen. Tissue oxygenation was measured using NIRS on the thumb. Subjects were blinded to breathing gas. A range of partial pressures of oxygen were administered in 10-min intervals: 21, 101, 21 kPa (compression to 280 kPa), 59, 280, 59 (decompression), 21 kPa. Data were averaged over last 5 min at each pressure. When switching from air to normobaric oxygen (NBO 101 kPa) StO₂ increased from 83% (82−85%, median and interquartile range) to 85% (84−87%) (P < 0.01), while when switching from air at pressure (59 kPa O₂) to HBO (280 kPa), StO₂ increased from 85% (85−86%) to 88% (87−89%) (P < 0.001). There was no difference between baseline StO₂ while air breathing before NBO or after decompression. Values did not reach the maximal value of 100% at any point. The changes in hemoglobin oxygen saturation in tissue registered by the NIRS monitor when switching from air to oxygen followed inspired PO₂ under normobaric and hyperbaric conditions.     

Oxygen breathing or recompression during decompression from nitrox dives with a rebreather: effects on intravascular bubble burden and ramifications for decompression profiles

Preventive measures to reduce the risk of decompression sickness can involve several procedures such as oxygen breathing during in-water decompression. Theoretical predictions also suggest that brief periods of recompression during the course of decompression could be a method for controlling bubble formation. The aim of this study was to get clearer information about the effects of different experimental ascent profiles (EAPs) on bubble reduction, using pure oxygen or recompression during decompression for nitrox diving. Four EAPs were evaluated using bubble monitoring in a group of six military divers using Nitrox 40% O(2) breathing with a rebreather. For EAP 1 and 2, 100% O(2) was used for the end stage of decompression, with a 30% reduction of decompression time in EAP 1 and 50% in EAP 2, compared to the French navy standard schedule. For EAP 3 and 4, nitrox 40% O(2) was maintained throughout the decompression stage. EAP 3 is based on an air standard decompression schedule, whereas EAP 4 involved a brief period of recompression at the end of the stop. We found that EAP 1 significantly reduced bubble formation, whereas high bubble grades occurred with other EAPs. No statistical differences were observed in bubbles scores between EAP 3 and 4. One diver developed mild neurological symptoms after EAP 3. These results tend to demonstrate that the "oxygen window" plays a key role in the reduction of bubble production and that breathing pure oxygen during decompression stops is an optimal strategy to prevent decompression sickness for nitrox diving.     

Aerobic exercise before diving reduces venous gas bubble formation in humans

We have previously shown in a rat model that a single bout of high-intensity aerobic exercise 20h before a simulated dive reduces bubble formation and after the dive protects from lethal decompression sickness. The present study investigated the importance of these findings in man. Twelve healthy male divers were compressed in a hyperbaric chamber to 280kPa at a rate of 100kPamin⁻¹ breathing air and remaining at pressure for 80min. The ascent rate was 9mmin⁻¹ with a 7min stop at 130kPa. Each diver underwent two randomly assigned simulated dives, with or without preceding exercise. A single interval exercise performed 24h before the dive consisted of treadmill running at 90% of maximum heart rate for 3min, followed by exercise at 50% of maximum heart rate for 2min; this was repeated eight times for a total exercise period of 40min. Venous gas bubbles were monitored with an ultrasonic scanner every 20min for 80min after reaching surface pressure. The study demonstrated that a single bout of strenuous exercise 24h before a dive to 18 m of seawater significantly reduced the average number of bubbles in the pulmonary artery from 0.98 to 0.22 bubbles cm⁻²  ( P = 0.006)  compared to dives without preceding exercise. The maximum bubble grade was decreased from 3 to 1.5  ( P = 0.002)  by pre-dive exercise, thereby increasing safety. This is the first report to indicate that pre-dive exercise may form the basis for a new way of preventing serious decompression sickness.     

Treatment of micro air bubbles in rat adipose tissue at 25 kPa altitude exposures with perfluorocarbon emulsions and nitric oxide

Introduction

Perfluorocarbon emulsions (PFC) and nitric oxide (NO) releasing agents have on experimental basis demonstrated therapeutic properties in treating and preventing the formation of venous gas embolism as well as increased survival rate during decompression sickness from diving. The effect is ascribed to an increased solubility and transport capacity of respiratory gases in the PFC emulsion and possibly enhanced nitrogen washout through NO-increased blood flow rate and/or the removal of endothelial micro bubble nuclei precursors. Previous reports have shown that metabolic gases (i.e., oxygen in particular) and water vapor contribute to bubble growth and stabilization during altitude exposures. Accordingly, we hypothesize that the administration of PFC and NO donors upon hypobaric pressure exposures either (1) enhance the bubble disappearance rate through faster desaturation of nitrogen, or in contrast (2) promote bubble growth and stabilization through an increased oxygen supply.

Methods

In anesthetized rats, micro air bubbles (containing 79 % nitrogen) of 4–500 nl were injected into exposed abdominal adipose tissue. Rats were decompressed in 36 min to 25 kPa (~10,376 m above sea level) and bubbles studied for 210 min during continued oxygen breathing (F_IO₂ = 1). Rats were administered PFC, NO, or combined PFC and NO.

Results

In all groups, most bubbles grew transiently, followed by a stabilization phase. There were no differences in the overall bubble growth or decay between groups or when compared with previous data during oxygen breathing alone at 25 kPa.

Conclusion

During extreme altitude exposures, the contribution of metabolic gases to bubble growth compromises the therapeutic effects of PFC and NO, but PFC and NO do not induce additional bubble growth.     

Prevention of air bubble formation in a microfluidic perfusion cell culture system using a microscale bubble trap

Formation of air bubbles is a serious obstacle to a successful operation of a long-term microfluidic systems using cell culture. We developed a microscale bubble trap that can be integrated with a microfluidic device to prevent air bubbles from entering the device. It consists of two PDMS (polydimethyldisiloxane) layers, a top layer providing barriers for blocking bubbles and a bottom layer providing alternative fluidic paths. Rather than relying solely on the buoyancy of air bubbles, bubbles are physically trapped and prevented from entering a microfluidic device. Two different modes of a bubble trap were fabricated, an independent module that is connected to the main microfluidic system by tubes, and a bubble trap integrated with a main system. The bubble trap was tested for the efficiency of bubble capture, and for potential effects a bubble trap may have on fluid flow pattern. The bubble trap was able to efficiently trap air bubbles of up to 10 μl volume, and the presence of captured air bubbles did not cause alterations in the flow pattern. The performance of the bubble trap in a long-term cell culture with medium recirculation was examined by culturing a hepatoma cell line in a microfluidic cell culture device. This bubble trap can be useful for enhancing the consistency of microfluidic perfusion cell culture operation.     

Oxygen pretreatment as protection against decompression sickness in rats: pressure and time necessary for hypothesized denucleation and renucleation

Pretreatment with HBO at 300–500 kPa for 20 min reduced the incidence of decompression sickness (DCS) in a rat model. We investigated whether this procedure would be effective with lower oxygen pressures and shorter exposure, and tried to determine how long the pretreatment would remain effective. Rats were pretreated with oxygen at 101 or 203 kPa for 20 min and 304 kPa for 5 or 10 min. After pretreatment, the animals were exposed to air at 1,013 kPa for 33 min followed by fast decompression. Pretreatment at 101 or 203 kPa for 20 min and 304 kPa for 10 min significantly reduced the number of rats with DCS to 45%, compared with 65% in the control group. However, after pretreatment at 304 kPa for 5 min, 65% of rats suffered DCS. When pretreatment at 304 kPa for 20 min was followed by 2 h in normobaric air before compression and decompression, the outcome was worse, with 70–90% of the animals suffering DCS. This is probably due to the activation of “dormant” micronuclei. The risk of DCS remained lower (43%) when pretreatment with 100% O₂ at normobaric pressure for 20 min was followed by a 2 h interval in normobaric air (but not 6 or 24 h) before the hyperbaric exposure. The loss of effectiveness after a 6 or 24 h interval in normobaric air is related to micronuclei rejuvenation. Although pretreatment with hyperbaric O₂ may have an advantage over normobaric hyperoxia, decompression should not intervene between pretreatment and the dive.     

An analysis of contact stiffness between a finger and an object when wearing an air-cushioned glove: the effects of the air pressure

Air-cushioned gloves have the advantages of lighter weight, lower cost, and unique mechanical performance, compared to gloves made of conventional engineering materials. The goal of this study is to analyze the contact interaction between fingers and object when wearing an air-cushioned glove. The contact interactions between the the fingertip and air bubbles, which is considered as a cell of a typical air-cushioned glove, has been analyzed theoretically. Two-dimensional finite element models were developed for the analysis. The fingertip model was assumed to be composed of skin layers, subcutaneous tissue, bone, and nail. The air bubbles were modeled as air sealed in the container of nonelastic membrane. We simulated two common scenarios: a fingertip in contact with one single air bubble and with two air cushion bubbles simultaneously. Our simulation results indicated that the internal air pressure can modulate the fingertip-object contact characteristics. The contact stiffness reaches a minimum when the initial air pressure is equal to 1.3 and 1.05 times of the atmosphere pressure for the single air bubble and the double air bubble contact, respectively. Furthermore, the simulation results indicate that the double air bubble contact will result in smaller volumetric tissue strain than the single air bubble contact for the same force.     

Dynamics of gas micronuclei formed on a flat hydrophobic surface,the predecessors of decompression bubbles

It is a long-standing hypothesis that the bubbles which evolve as a result of decompression have their origin in stable gas micronuclei. In a previous study (Arieli and Marmur, 2011), we used hydrophilic and monolayer-covered hydrophobic smooth silicon wafers to show that nanobubbles formed on a flat hydrophobic surface may be the gas micronuclei responsible for the bubbles that evolve to cause decompression sickness. On decompression, bubbles appeared only on the hydrophobic wafers. The purpose of the present study was to examine the dynamics of bubble evolution. The numbers of bubbles after decompression were greater with increasing hydrophobicity. Bubbles appeared after decompression from 150 kPa, and their density increased with elevation of the exposure pressure (and supersaturation), up to 400 kPa. The normal force of attraction between the hydrophobic surface and the bubble, as determined from the volume of bubbles leaving the surface of the wafer, was 38 × 10^?5 N and the tangential force was 20 × 10^?5 N. We discuss the correlation of these results with previous reports of experimental decompression and bubble formation, and suggest to consider appropriate modification of decompression models.     

Comparison of haemodynamic effects during venous air infusion and after decompression in pigs

We have compared haemodynamic effects of venous gas emboli during continuous air infusion into the right atrium and after rapid decompression in pigs. Eight anaesthetized and spontaneously breathing pigs received continuous air infusion at a rate of either 0.05 ml·kg^–1 · min^–1 (six pigs, air infusion group) or 0.10 ml·kg^–1 · min^–1 (two pigs). Another eight pigs (decompression group) underwent a 30-min compression to 5 bar (500 kPa, absolute pressure), followed by a rapid decompression (2 bar·min^–1). Haemodynamic variables were measured or calculated, and bubbles in the pulmonary artery were monitored using transoesophageal echocardiography. The results showed less variation in the maximal increase in mean pulmonary arterial pressure ( _{a, pulm}) during air infusion (0.05 ml·kg^–1 · min^–1) than after decompression, although the mean maximal increase did not differ between the two groups [28.0 mmHg (3.73 kPa), 95% confidence interval (CI) 23.5–32.5, vs 32.0 mmHg (4.27 kPa), 95% CI 25.3-38.7, P=0.3]. The _a,pulm stabilized or decreased very slowly after peak values were reached in the air infusion group, whereas the _a,pulm decreased rapidly during the same period in the decompression group. No significant changes in mean arterial pressure were observed during air infusion (0.05 ml· kg^–1 · min^–1), in contrast to the rapid increase and the subsequent decrease, that appeared after decompression. Finally, the maximal bubble count was much lower in the air infusion group than in most of the pigs in the decompression group. The two pigs that received 0.10 ml·kg^–1 · min^–1 stopped breathing after 5-min infusion, developed arterial hypotension and died.     

Measurements and Theory of Normal Tracheal Breath Sounds

We studied the mechanisms by which turbulent flow induces tracheal wall vibrations detected as tracheal breath sounds (TRBSs). The effects of flow rate at transitional Reynold's numbers (1300–10,000) and gas density on spectral patterns of TRBSs in eight normal subjects were measured. TRBSs were recorded with a contact sensor during air and heliox breathing at four flow rates (1.0, 1.5, 2.0, and 2.5 l/s). We found that normalized TRBSs were proportional to flow to the 1.89 power during inspiration and to the 1.59 power during expiration irrespective of gas density. The amplitude of TRBSs with heliox was lower than with air by a factor of 0.33 ± 0.12 and 0.44 ± 0.16 during inspiration and expiration, respectively. The spectral resonance frequencies were higher during heliox than air breathing by a factor of 1.75 ± 0.2—approximately the square root of the reciprocal of the air/heliox wave propagation speed ratio. In conclusion, the flow-induced pressure fluctuations inside the trachea, which cause tracheal wall vibrations, were detected as TRBSs consist of two components: (1) a dominant local turbulent eddy component whose amplitude is proportional to the gas density and nonlinearly related to the flow; and (2) a propagating acoustic component with resonances whose frequencies correspond to the length of the upper airway and to the free-field sound speed. Therefore, TRBSs consist primarily of direct turbulent eddy pressure fluctuations that are perceived as sound during auscultation.     

Ultrastructural aspects of bubble formation in human fatal accidents after exposure to compressed air

Summary Electron microscopic investigations were performed on samples of human tissue obtained from subjects following fatal decompression sickness, associated with hyperbaric air-therapy. Intra- and extracellular gas bubbles of varying size were identified throughout the entire body. Each bubble was covered by an osmiophilic non-homogeneous coat of cloudy and flocculent material, native to its specific locality. This envelope measured from 30 to 560 Angstroem-units in thickness. Association of this covering with an electrokinetic zonal activity, detected biophysically by Lee and Hairston (1971) is assumed. We consider this surface coat prevents nitrogen from being eliminated via the blood-lung-barrier.     

Decompression sickness bubbles: Are gas micronuclei formed on a flat hydrophobic surface?

It is a long-standing hypothesis that the bubbles which evolve as a result of decompression have their origin in stable gas micronuclei lodged in hydrophobic crevices, micelles of surface-active molecules, or tribonucleation. Recent findings supported by atomic force microscopy have indicated that tiny, flat nanobubbles form spontaneously on smooth, hydrophobic surfaces submerged in water. We propose that these nanobubbles may be the gas micronuclei responsible for the bubbles that evolve to cause decompression sickness. To support our hypothesis, we used hydrophilic and monolayer-covered hydrophobic smooth silicon wafers. The experiment was conducted in three main stages. Double distilled water was degassed at the low pressure of 5.60 kPa; hydrophobic and hydrophilic silicon wafers were placed in a bowl of degassed water and left overnight at normobaric pressure. The bowl was then placed in the hyperbaric chamber for 15 h at a pressure of 1013 kPa (=90 m sea water). After decompression, bubbles were observed and photographed. The results showed that bubbles only evolved on the hydrophobic surfaces following decompression. There are numerous hydrophobic surfaces within the living body (e.g., in the large blood vessels), which may thus be the sites where nanobubbles that serve as gas micronuclei for bubble evolution following decompression are formed.     

Exercise and nitric oxide prevent bubble formation: a novel approach to the prevention of decompression sickness?

Nitrogen dissolves in the blood during dives, but comes out of solution if divers return to normal pressure too rapidly. Nitrogen bubbles cause a range of effects from skin rashes to seizures, coma and death. It is believed that these bubbles form from bubble precursors (gas nuclei). Recently we have shown that a single bout of exercise 20 h, but not 48 h, before a simulated dive prevents bubble formation and protects rats from severe decompression sickness (DCS) and death. Furthermore, we demonstrated that administration of N ^ω-nitro- l -arginine methyl ester, a non-selective inhibitor of NO synthase (NOS), turns a dive from safe to unsafe in sedentary but not exercised rats. Therefore based upon previous data an attractive hypothesis is that it may be possible to use either exercise or NO-releasing agents before a dive to inhibit bubble formation and thus protect against DCS. Consequently, the aims of the present study were to determine whether protection against bubble formation in 'diving' rats was provided by (1) chronic and acute administration of a NO-releasing agent and (2) exercise less than 20 h prior to the dive. NO given for 5 days and then 20h prior to a dive to 700 kPa lasting 45 min breathing air significantly reduced bubble formation and prevented death. The same effect was seen if NO was given only 30 min before the dive. Exercise 20h before a dive surpressed bubble formation and prevented death, with no effect at any other time (48, 10, 5 and 0.5h prior to the dive). Pre-dive activities have not been considered to influence the growth of bubbles and thus the risk of serious DCS. The present novel findings of a protective effect against bubble formation and death by appropriately timed exercise and an NO-releasing agent may form the basis of a new approach to preventing serious decompression sickness.     

Brain hypothermia induced by cold spinal fluid using a torso cooling pad: theoretical analyses

Brain hypothermia induced by a temperature reduction of the spinal fluid using a torso-cooling pad is evaluated as a cooling alternative for traumatic injury patients. A theoretical model of the human head is developed to include its tissue structures and their contribution to local heat transfer. The Pennes bioheat equation and finite element analysis are used to predict the temperature distribution in the head region. The energy balance in the cerebrospinal fluid (CSF) layer surrounding the brain during mixing of the CSF and cold spinal fluid is also formulated to predict the CSF temperature reduction. Results show that the presence of cooled CSF around the brain provides mild cooling (~1°C) to the grey matter within 3000 s (50 min) with a cooling capacity of approximately 22 W. However, large temperature variations (~3.5°C) still occur in the grey matter. This approach is more effective during ischemia because it promotes deeper cooling penetration and results in larger temperature reductions; the average grey matter temperature decreases to 35.4°C. Cooling in the white matter is limited and only occurs under ischemic conditions. The non-invasive nature of the torso-cooling pad and its ability to quickly induce hypothermia to the brain tissue are beneficial to traumatic injury patients.     

Behavior of gaseous microemboli in extracorporeal circuits: air versus CO2

BACKGROUND: Open heart surgery is associated with serious risk of cerebral and peripheral organ dysfunction, attributed in part to air microbubbles generated in or not eliminated from the extracorporeal circuit (ECC). Venous air leakage leads to increased arterial bubble load. CO2 replacing air in cardiac chambers show faster resorption times, reducing possible cerebral or peripheral organ damage after heart valve interventions. In two models of ECC the effect of air entering closed circuits was demonstrated and compared to the effect of CO2 entry. METHODS: Fragmentation and dissolution of gas (0.5 mL) was evaluated in an in vitro model of ECC, using ultrasonic bubble detection. Air leakage (10 mL) in the venous line of the ECC was simulated and compared to the effect of the same quantity of CO2 entering the circuit. Both models used whole blood priming and physiological conditions, verified with blood gas analyses. RESULTS: Fragmentation and dissolution of gas bubbles injected into a closed ECC could be demonstrated, complete resorption of CO2 bubbles was observed earlier than complete resorption of room air (5.0+/-0.6 vs. 14.4+/-5.9 min, p=0.0009). CO2 entering the venous line lead to 40% less arterial bubble load as compared to the same amount of room air entering the circuit (2099+/-991 vs. 3555+/-632, p=0.005). CONCLUSIONS: Current ECC systems fail to eliminate gas entering the circuit, leading rather to microbubble dispersion. CO2 is much faster resorbed within the circuit than room air. In open heart surgery as valvular operations, CO2 insufflation into the operative field is protective, as we have demonstrated in our models.     

Glia to neuron ratio in the posterior aspect of the human spinal cord at thoracic segments relevant to spinal cord stimulation

Spinal cord stimulation (SCS) applied between T8 and T11 segments has been shown to be effective for the treatment of chronic pain of the lower back and limbs. However, the mechanism of the analgesic effect at these medullary levels remains unclear. Numerous studies relate glial cells with development and maintenance of chronic neuropathic pain. Glial cells are electrically excitable, which makes them a potential therapeutic target using SCS. The aim of this study is to report glia to neuron ratio in thoracic segments relevant to SCS, as well as to characterize the glia cell population at these levels. Dissections from gray and white matter of posterior spinal cord segments (T8, T9, intersection T9/T10, T10 and T11) were obtained from 11 human cadavers for histological analyses. Neuronal bodies and glial cells (microglia, astrocytes and oligodendrocytes) were immunostained, microphotographed and counted using image analysis software. Statistical analyses were carried out to establish significant differences of neuronal and glial populations among the selected segments, between the glial cells in a segment, and glial cells in white and gray matter. Results show that glia to neuron ratio in the posterior gray matter of the human spinal cord within the T8–T11 vertebral region is in the range 11 : 1 to 13 : 1, although not significantly different among vertebral segments. Glia cells are more abundant in gray matter than in white matter, whereas astrocytes and oligodendrocytes are more abundant than microglia (40 : 40 : 20). Interestingly, the population of oligodendrocytes in the T9/T10 intersection is significantly larger than in any other segment. In conclusion, glial cells are the predominant bodies in the posterior gray and white matter of the T8–T11 segments of the human spinal cord. Given the crucial role of glial cells in the development and maintenance of neuropathic pain, and their electrophysiological characteristics, anatomical determination of the ratio of different cell populations in spinal segments commonly exposed to SCS is fundamental to understand fully the biological effects observed with this therapy.     

Graded unilateral cervical spinal cord injury and respiratory motor recovery

We examined the potential contribution of ventromedial (VM) tissue sparing to respiratory recovery following chronic (1 mo) unilateral C2 spinal cord injury (SCI) in rats. Preserved white matter ipsilateral to the injury was quantitatively expressed relative to contralateral white matter. The ipsilateral-to-contralateral white matter ratio was 0 after complete C2 hemisection (C2HS) and 0.23 ± 0.04 with minimal VM sparing. Inspiratory (breath min⁻¹) and phrenic frequency (burst min⁻¹), measured by plethysmography (conscious rats) and phrenic neurograms (anesthetized rats) respectively, were both lower with minimal VM sparing (p < 0.05 vs. C2HS). Tidal volume also was greater in minimal VM sparing rats during a hypercapnic challenge (p < 0.05 vs. C2HS). In other C2 hemilesioned rats with more extensive VM matter sparing (ipsilateral-to-contralateral white matter ratio = 0.55 ± 0.05), respiratory deficits were indicated at 1 mo post-injury by reduced ventilation during hypercapnic challenge (p < 0.05 vs. uninjured). Anterograde (ventral respiratory column-to-spinal cord) neuroanatomical tracing studies showed that descending respiratory projections from the brainstem are present in VM tissue. We conclude that even relatively minimal sparing of VM tissue after C2 hemilesion can alter respiratory outcomes. In addition, respiratory deficits can emerge in the adult rat after high cervical SCI even when relatively extensive VM sparing occurs.     

Mathematical Model of Diffusion-Limited Evolution of Multiple Gas Bubbles in Tissue

Models of gas bubble dynamics employed in probabilistic analyses of decompression sickness incidence in man must be theoretically consistent and simple, if they are to yield useful results without requiring excessive computations. They are generally formulated in terms of ordinary differential equations that describe diffusion-limited gas exchange between a gas bubble and the extravascular tissue surrounding it. In our previous model (Ann. Biomed. Eng. 30: 232–246, 2002), we showed that with appropriate representation of sink pressures to account for gas loss or gain due to heterogeneous blood perfusion in the unstirred diffusion region around the bubble, diffusion-limited bubble growth in a tissue of finite volume can be simulated without postulating a boundary layer across which gas flux is discontinuous. However, interactions between two or more bubbles caused by competition for available gas cannot be considered in this model, because the diffusion region has a fixed volume with zero gas flux at its outer boundary. The present work extends the previous model to accommodate interactions among multiple bubbles by allowing the diffusion region volume of each bubble to vary during bubble evolution. For given decompression and tissue volume, bubble growth is sustained only if the bubble number density is below a certain maximum. © 2003 Biomedical Engineering Society. PAC2003: 8719Uv, 8710+e, 8715Vv, 8719Xx