THE ELUSIVE BUBBLE

B.R. Wienke
Applied Theoretical Physics Division
Los Alamos National Laboratory Los Alamos, N.M. 87545

"Dilemmas"
Biophysical models of inert gas transport and bubble formation all try to prevent decompression sickness. Developed over years of diving application, they differ on a number of basic issues, still mostly unresolved today:

1. the rate limiting process for inert gas exchange, blood flow rate (perfusion) or gas transfer rate across tissue (diffusion);

2. composition and location of critical tissues (bends sites);

3. the mechanistics of phase inception and separation (bubble formation and growth);

4. the critical trigger point best delimiting the onset of symptoms (dissolved gas buildup in tissues, volume of separated gas, number of bubbles per unit tissue volume, bubble growth rate to name a few);

5. the nature of the critical insult causing bends (nerve deformation, arterial blockage or occlusion, blood chemistry or density changes).

Such issues confront every modeler and table designer, quite perplexing in their ambiguous correlations with experiment and nagging in their persistence. For every answer to these questions, others can be proposed, refuting the first. It is also very difficult to do the necessary experiments in living tissue to resolve issues. And here discussion is confined just to bubbles and Type I and II bends, to say nothing of other factors and types. The substance of these questions ultimately links to bubbles, that is, how they are formed, where they grow, when they move, and how they are eliminated. The dilemmas are formidable.

"Bubble Sites"
We do not really know where bubbles form nor lodge, their migration patterns, their birth and dissolution mechanisms, nor the exact chain of physico-chemical insults resulting in decompression sickness. Many possibilities exist, differing in the nature of the insult, the location, and the manifestation of symptoms. Bubbles might form directly (de~novo) in supersaturated sites upon decompression, or possibly grow from preformed, existing seed nuclei excited by compression-decompression. Leaving their birth sites, bubbles may move to critical sites elsewhere. Or stuck at their birth sites, bubbles may grow locally to pain-provoking size. They might dissolve locally by gaseous diffusion to surrounding tissue or blood, or passing through screening filters, such as the lung complex, they might be broken down into smaller aggregates, or eliminated completely. Whatever the bubble history, it presently escapes complete elucidation.

Bubbles may hypothetically form in the blood (intravascular) or outside the blood (extravascular). Once formed, intravascularly or extravascularly, a number of critical insults are possible. Intravascular bubbles may stop in closed circulatory vessels and induce blood sludging and chemistry degradations (ischemia), or mechanical nerve deformation. Circulating gas emboli may occlude the arterial flow, clog the pulmonary filters, or leave the circulation to lodge in tissue sites as extravasular bubbles. Extravascular bubbles may remain locally in tissue sites, assimilating gas by diffusion from adjacent supersaturated tissue and growing until a nerve ending is deformed beyond its pain threshold. Or, extravascular bubbles might enter the arterial or venous flows, at which point they become intravascular bubbles.

Spontaneous bubble formation in fluids usually requires large decompressions, like hundreds of atmospheres, somewhere near fluid tensile limits. Many feel that such circumstance precludes direct bubble formation in blood following decompression. Explosive, or very rapid decompression, of course is a different case. But, while many doubt that bubbles form in the blood directly, intravascular bubbles have been seen in both the arterial and venous circulation, with vastly greater numbers detected in venous flows (venous gas emboli). Ischemia resulting from bubbles caught in the arterial network has long been implied as a cause of decompression sickness. Since the lungs are effective filters of venous bubbles, arterial bubbles would then most likely originate in the arteries or adjacent tissue beds. The more numerous venous bubbles, however, are suspected to first form in lipid tissues draining the veins. Lipid tissue sites also possess very few nerve endings, possibly masking critical insults. Veins, thinner than arteries, appear more susceptible to extravascular gas penetration.

Extravascular bubbles may form in aqueous (watery) or lipid (fatty) tissues in principle. For all but extreme or explosive decompression, bubbles are seldom observed in heart, liver, and skeletal muscle. Most gas is seen in fatty tissue, not unusual considering the five-fold higher solubility of nitrogen in lipid tissue versus aqueous tissue. Since fatty tissue has few nerve endings, tissue deformation by bubbles is unlikely to cause pain locally. On the other hand, formations or large volumes of extravascular gas could induce vascular hemorrhage, depositing both fat and bubbles into the circulation as noted in animal experiments. If mechanical pressure on nerves is a prime candidate for critical insult, then tissues with high concentrations of nerve endings are candidate structures, whether tendon or spinal cord. While such tissues are usually aqueous, they are invested with lipid cells whose propensity reflects total body fat. High nerve density and some lipid content supporting bubble formation and growth would appear a conducive environment for a mechanical insult.

On the question of preformed nuclei, their presence in human tissue and blood has not been demonstrated. The existence of preformed nuclei in serum and egg albumin has been reported by Yount and Strauss. Since performed nuclei are found virtually in every aqueous substance known, their preclusion from the body would come as a surprise to many. Hence, while most regard nucleation as a random process, its occurrence in tissue seems highly probable, seen for instance in the studies of Evans, Walder, Strauss, Yount, Kunkle, and co-workers. Model correlations with incidence statistics of decompression sickness in salmon, rats, and humans speak favorably for the nucleation concept.

The ultimate computational algorithm, coupling nucleation, dissolved gas uptake and elimination, bubble growth and collisional coalescence, and critical sites, would be very, very complicated, requiring supercomputers (like CRAYs, CYBERs, VPs, CONVEXs, and ESSEXs, or their massively parallel cousins, CMs, NCUBESs, IWARPs, and DAPs) for three dimensional modeling. Stochastic Monte Carlo methods and sampling techniques exist which could generate and stabilize nuclei from thermodynamic functions, such as the Gibbs or Helmholtz free energy, transport dissolved gas in flowing blood to appropriate sites, inflate, deflate, move, and collide bubbles and nuclei, and then tally statistics on tensions, bubble size and number, inflation and coalescence rate, free phase volume, and any other meaningful parameter, all in necessary geometries. Such type simulations of similarly complicated problems last for 16-32 hours at the Los Alamos and Livermore National Laboratories, on lightning fast supercomputers with near gigaflop speed (10 sup 9 floating point operations per second). While decompression meters have revolutionized diving and decompression calculations, it will be some time before the ultimate computational algorithm fits into a wrist computer.

"Venous Gas Emboli"
Sound reflected off a moving boundary undergoes a shift in acoustical frequency, the so-called Doppler shift. The shift is directly proportional to the speed of the moving surface (component in the direction of sound propagation) and the acoustical frequency of the wave, and inversely proportional to the sound speed. Acoustical signals in the megahertz range (10 sup 6 vibrations per second), termed ultrasound, have been directed at moving blood in the pulmonary arteries, where blood flow rates are the highest (near 20 cm/sec) due to confluence of the systemic circulation, with resulting Doppler shifts, in the form of audible chirps, snaps, whistles, and pops, noted and recorded. Sounds heard in divers have been ascribed to venous gas emboli (VGE), and in~vitro studies (gels) and have established minimum bubble detection size as a function of blood velocity. Coalesced lipids, platelet aggregates, and agglutinated red blood cells formed during decompression also pass through the pulmonary circulation, but are less reflective than bubbles, and usually smaller. Bubbles with radii in the tens of micron (10 sup -4 cm) range represent a cutoff for Doppler detection for signals of a few megahertz.

Ultrasonic techniques for monitoring moving gas emboli in the pulmonary circulation are popular today. Silent bubbles, as applied to the venous gas emboli detected in sheep undergoing bends-free USN table decompression by Spencer and Campbell, were a first indication that asymptomatic free phases were present in blood, even under bounce loadings. Similar results were reported by Walder and Evans. After observing and contrasting venous gas emboli counts for various nonstop exposures at depth, Spencer suggested that nonstop limits be reduced below the USN table limits. Enforcing a 20% drop in venous gas emboli counts compared to the USN limits, corresponding nonstop limits, t sub s , at depth, d, satisfy a reduced Hempleman relationship, that is, d t sub s sup 1/2 = 465 fsw min sup 1/2. Plugging those nonstop limits into the Haldane tissue equations for all depths and across all compartments, followed by extraction of the maximum of ensuing computed tissue tensions, permits construction of a reduced set of limiting tensions for table or meter implementation. Such exercises are quite popular today, and certainly prudent.

While the numbers of venous gas emboli detected with ultrasound Doppler techniques can be correlated with nonstop limits, and the limits then used to fine tune the critical tension matrix for select exposure ranges, fundamental issues are not necessarily resolved by venous gas emboli measurements. First of all, venous gas emboli are probably not the direct cause of bends per se, unless they block the pulmonary circulation, or pass through the pulmonary traps and enter the arterial system to lodge in critical sites. Intravascular bubbles might first form at extravascular sites. According to Hills, electron micrographs have highlighted bubbles breaking into capillary walls from adjacent lipid tissue beds in mice. Fatty tissue, draining the veins and possessing few nerve endings, is thought to be an extravascular site of venous gas emboli. Similarly, since blood constitutes no more than 8% of the total body capacity for dissolved gas, the bulk of circulating blood does not account for the amount of gas detected as venous gas emboli. Secondly, what has not been established is the link between venous gas emboli, possible micronuclei, and bubbles in critical tissues. Any such correlations of venous gas emboli with tissue micronuclei would unquestionably require considerable first-hand knowledge of nuclei size distributions, sites, and tissue thermodynamic properties. While some believe that venous gas emboli correlate with bubbles in extravascular sites, such as tendons and ligaments, and that venous gas emboli measurements can be reliably applied to bounce diving, the correlations with repetitive and saturation diving have not been made to work, nor important correlations with more severe forms of decompression sickness, such as chokes and central nervous system (CNS) hits.

Still, whatever the origin of venous gas emboli, procedures and protocols which reduce gas phases in the venous circulation deserve attention, for that matter, anywhere else in the body. The moving Doppler bubble may not be the bends bubble, but perhaps the difference may only be the present site. The propensity of venous gas emboli may reflect the state of critical tissues where decompression sickness does occur. Studies and tests based on Doppler detection of venous gas emboli are still the only viable means of monitoring free phases in the body.