Diving too carefully?

[Simon Mitchell]

So, removing the descriptive differences and little semantic differences, between Neal and I, what I have said is substantially correct.

Ross, your lack of comprehension of tactful yet simple prose is scarcely believable and frankly scary. You have just been told you are wrong on several of your fundamental stands on this thread (and others) by an independent expert who (commensurate with his role in DAN etc) is trying to be as tactful as possible, and yet somehow you manage to construe the opposite meaning??

Using the order of things in Neal's post as a template:

The fact that they use a half way point, means that when real world variations in VGE are applied, many divers will have VGE scores that exceed this mid point.

Grade I and II VGE were tolerated within the limits of the DCIEM tables not because they were any kind of "half way point," but because they have less association with symptomatic DCS than grade III and IV VGE do (followed by an explanation of ordinal scales).....

__________________________________________________________________________________________________________

VGE have been with us forever, and theory states they grow in the venous system from dissolved gas. Note its the veins, and not the tissue. These do not make DCS in normal people. Tissue microbubble are thought to grow in the tissue, from doing deco too fast, and are the ones that create DCS.

Efforts to suggest that intravascular bubbles are somehow a completely unique thing does not make sense.

__________________________________________________________________________________________________________

VGE is a secondary measure, that is indirectly proportional to the primary measure of gas content and saturation

Bubbles are a secondary measure of decompression stress, but a point that was lost is that the primary measure is symptomatic DCS, not gas content. While it is true that the vast majority of divers have not been scanned for bubbles post-dive, it is a greater truth that no divers have their total gas content measured. Decompression algorithms predict gas uptake and elimination across a range of theoretical tissue compartments. This is not a primary measure.

__________________________________________________________________________________________________________

I'll cross post this quote here, because Neal's visit to this forum is a rare visit by one of my "peers" whose opinions you raise:

http://www.rebreatherworld.com/showthread.php?46994-Deep-stops-debate-(split-from-ascent-rate-thread)&p=440217&viewfull=1#post440217

After 40 years of studies and many reports by many of your peers and seniors, the conclusions come down to:

VGE is common place.
VGE cannot predict DCS, except when associated with extreme profile abuse.
VGE at any level, will not produce DCS.

Those three points are repeated time and again

We do not treat VGE but we have a much higher expectation of DCS as VGE scores climb.

Neal, of course, is merely confirming what I said in relation to the Nishi data a few posts back.
_________________________________________________________________________________________________________

As I discussed above, VGE is not a good measure and adds nothing to DCS avoidance. VGE has been ignored for these reasons for 40+ years since Spencer found then in the early 70's. No new information is available by watching VGE, so they should be ignored

Neal presents two of his contemporary studies using VGE as an outcome measure (which I take to mean he does not ignore them), and then states:

Intravascular bubbles are not the perfect measure, but they provide insights that certainly are not discounted in the scientific community. Similarly, they should not be discounted in the diving community.

The above two quotes from Neal are probably the most important. Although you have tried to twist and turn it in several directions, this debate started in relation to, and for me has always been about, your claim that VGE are harmless and can be ignored. It is abundantly clear to anyone (except perhaps you) from his commentary that Neal (like me) does NOT agree with you.

I would be most happy for Neal to correct me if I have misrepresented any of his views.

Simon M

 

[Randy Thornton]

Thank you Neal for your participation!

As you are aware, Josh, Michael and I have participated in your study a number of times. I personally found the bubble study to be very interesting and it has caused me to change the shape of my decompression. Due to the results of several days of high bubble scores, I elected to move from a deep stop oriented deco to more of a shallow with long tail type stop which seemed to lessen the amount and size of VGE. Most interesting for me has been the fact that I generally feel better with this latter type of deco - less fatigue and less niggles. Although it has now been a couple of years since I participated in your bubble study, it has impacted my personal decision making with regard to GF choices.

I know that the study was not designed to necessarily encourage change, but none the less, when I saw a significant amount of decompression stress in the form of high grade VGE going on, I couldn't help but experiment with taking steps to lower the stress. Fortunately for me, it has been the right decision as I now feel much healthier and happier after long deep dives!

Thanks again for your insight here on CCRX! I look forward to hearing more from you.

Kind regards,
Randy
(Formerly, "Mr. Invinsible"!)

 

[rossh]

Using the order of things in Neal's post as a template:

Simon M

1/ First one ... semantics.... half way - mid point - fussing over exact half way place - semantics...

2 / The location of VGE growth - is well documented by others as venous... Neal does not deny this.

3/ Neal and my comments agree, but differs on description of technical terms .... semantics again.

4/ You have twisted comments again to suit yourself.... What I said is correct. and agrees with Neals comments.

5/ Agreement over non-accuracy, disagreement over usefulness.


Total: 2 x semantics, 2 x agreement, 1 half way


All you have and semantics and tricks and deception and insults Simon.

What I said and think is substantially in agreement with Neal. I quoted him often in the RBW thread. I value his opinion, because he sticks the science and doesn't twist it with spin. He seems to want to promote safer diving practices which is OK too.

You on the other hand, spin, twist distort the science, and play scare tactics, insult anyone who gets in the way. You have demonstrated time and again that you are not reliable as a source of facts.

 

[npollock]

I appreciate you sharing your experience, Randy. If others choose to weigh in it will be helpful if they clarify the structure of the scanning they experienced. I say this because the results of a single scan at an uncontrolled point with less powerful equipment is likely to be far less informative than sampling every 20 minutes for two hours with skilled technicians and high fidelity equipment that form the backbone of our studies. Perhaps another thread....

One minor correction to make sure that no one is confused. The current ultrasonic monitoring technology (aural Doppler or two-dimensional echo) used to study decompression-induced bubbles in divers enables bubble counts, but not sizing. The dual frequency ultrasound that is in development has the potential to change this, but the current reality is that estimates of bubble size or total gas volume exceed our capabilities. Any statements concerning size and volume are hand-waving, and must be viewed very cautiously.

 

[npollock]

Unfortunately, Ross, I do not believe that our core positions are in agreement. The differences are much greater than simply semantic.

The reduced concern over grade I and II VGE is because they generally have no statistical relationship with DCS. There are six grades above that point in our current grading scale. Suggesting that they constitute anything close to a mid-point is not valid.

Bubbles do form in most if not all tissues, but intravascular bubbles (VGE, to use the common terminology) serve as a good indicator of decompression stress. Seeing intravascular bubbles likely indicates bubble formation in other tissues. Suggesting that other tissues are experiencing radically different conditions that blood tissues experience is not valid.

I think it would be best if you state your position and not tell others what you believe to be my position.

 

[Igor P]

The field dive monitoring project with technical divers is ongoing. Because the work is observational (we monitor but do not control the exposures) it takes a long time to fill out the picture.

Thank's Neal! Hope to read final report and conclusions/picture from monitoring.

Igor P


Sent from my PAP4500DUO using Tapatalk 2

 

[Michael Thornton]

One minor correction to make sure that no one is confused. The current ultrasonic monitoring technology (aural Doppler or two-dimensional echo) used to study decompression-induced bubbles in divers enables bubble counts, but not sizing. The dual frequency ultrasound that is in development has the potential to change this, but the current reality is that estimates of bubble size or total gas volume exceed our capabilities. Any statements concerning size and volume are hand-waving, and must be viewed very cautiously.

With high grade bubbles (the ones that look like a white out on the screen) what keeps so many bubbles from joining together into larger bubbles? What could cause them to join together into larger bubbles?



Sent from my iPhone using Tapatalk

 

[npollock]

Given sufficient time and proximity bubbles can merge. Ultrasound images can be misleading, though. The grade V 'whiteout' may not be a true whiteout in terms of bubbles touching each other. Bubbles are highly reflective of sound energy, making them highly visible, but not necessarily accurately reflecting size or proximity to adjacent bubbles. This is a big part of why they should not be used to estimate gas volumes (in addition to the challenge of using a two-dimensional plane to estimate a dynamic three-dimensional volume). So, ultimately, we can do a good job grading relative bubble concentrations, for example, we can see when the load in a scan looks more like a IVb than a IVc, for example, but we try not to overstate the meaning of this.

 

[Randy Thornton]

One minor correction to make sure that no one is confused. The current ultrasonic monitoring technology (aural Doppler or two-dimensional echo) used to study decompression-induced bubbles in divers enables bubble counts, but not sizing.

Thanks for the clarification Neal.

 

[rossh]

Neal , Sorry if you feel I was stating you position - not intended.


grade 2, grade 6, mid point, etc, I was not trying to identify the precise half way position. The point of my original comment was to show that by selecting some approximate mid point, it causes individuals to experience both more and less VGE due the wide variations each individual posses. Does that help?

intravascular bubbles (VGE, to use the common terminology)

in·tra·vas·cu·lar
***716;intr***601;***712;vasky***601;l***601;r/
adjectiveMedicineBiology
adjective: intravascular

situated or occurring within a vessel or vessels of an animal or plant, especially within a blood vessel or blood vascular system.

I believe this is the common location described in most theory of VGE for seeds to grow, usually described as caveolae in the endothilum. Another description I read is the venous end of capillary beds. Do you agree with that?

Which I believe is different in location of normal DCS microbubble growth, usually described as formation of microbubbles within the tissues themselves. Do you agree with that?

I believe the above. It's documented that way. I used Bennett Elliot, Bruback reference there.



Simon on the other hand, wants to merge the two together as one, so he can twist more facts out of context.

 

[Simon Mitchell]

Ross,

This is getting silly now.

What I said and think is substantially in agreement with Neal. I quoted him often in the RBW thread. I value his opinion, because he sticks the science and doesn't twist it with spin. He seems to want to promote safer diving practices which is OK too.

Unfortunately, Ross, I do not believe that our core positions are in agreement. The differences are much greater than simply semantic.

How much clearer does it need to be made to you?

And in respect to this....

I believe this is the common location described in most theory of VGE for seeds to grow, usually described as caveolae in the endothilum. Another description I read is the venous end of capillary beds. Do you agree with that?

Which I believe is different in location of normal DCS microbubble growth, usually described as formation of microbubbles within the tissues themselves. Do you agree with that?

Your end game here is to try to lure Neal into supporting your view that VGE don't matter because it is "tissue bubbles" that cause DCS. I don't think you will have much luck with that. You have had it explained to you multiple times that trying to imply that VGE counts are not relevant to supersaturation conditions in tissues (and therefore not relevant to the propensity for bubbles to form in tissues) is wrong. In any event, you already have Neal's answer....

Efforts to suggest that intravascular bubbles are somehow a completely unique thing does not make sense.

Simon M

 

[rossh]

Given sufficient time and proximity bubbles can merge. Ultrasound images can be misleading, though. The grade V 'whiteout' may not be a true whiteout in terms of bubbles touching each other. Bubbles are highly reflective of sound energy, making them highly visible, but not necessarily accurately reflecting size or proximity to adjacent bubbles. This is a big part of why they should not be used to estimate gas volumes (in addition to the challenge of using a two-dimensional plane to estimate a dynamic three-dimensional volume). So, ultimately, we can do a good job grading relative bubble concentrations, for example, we can see when the load in a scan looks more like a IVb than a IVc, for example, but we try not to overstate the meaning of this.

Neal, can you comment on some of this please?

Have you had the chance to observe side by side Nitrogen only dives vs Helium or trimix dives? For the same approximate equal deco schedules in each, do you see a difference in VGE loads? Is the helium diver likely to make more VGE? Do you get any general sense of difference in VGE bubble sizes between the two gas types?


Thanks rossh

 

[npollock]

Ross,

As was discussed very early in this thread, the absence of VGE is associated with an extremely low risk of DCS. It would be best if all dives were bubble-free, it is simply not practical design a conservative enough profile to ensure that state for all divers. The willingness to tolerate some risk is a necessary evil of moving through the world. The simplest analogy might be a speed limit. There is no doubt that having everyone drive very slowly would reduce the risk of speed-related accidents, it just becomes impractical at some point. Current decompression algorithms can provide enough rope for our analogous driver to be going at race pace. Similar to the dive computer, the pace alone sets only some of the risk, since factors like surface slickness (rain or ice) can hugely affect the risk of any speed. Moving it back to bubbles, my point is simple - it is safer to have the lowest grade of bubbles possible. Zero is good, especially if modest changes in practice can help get you there.

Regarding bubble formation, it is likely a pretty similar process in any tissue. There needs to be sufficient supersaturation and some type of nidus that supports the formation. It is not valid to talk about microbubbles in the bloodsteam as different from microbubbles in any other tissue. The reason they tend to form in the systemic venous system as opposed to the systemic arterial system is because the gas tension is higher in the systemic venous system. The gas tension is markedly lower on the systemic arterial side since gas exchange has occurred in the alveoli. The lower nitrogen tension in the left heart is almost certainly why the left heart bubbles that we saw in 13% of the dives we talked about in the second abstract I shared do not cause more problems. A good example of physics and physiology working together.

(Note: I talk about "systemic arterial" instead of just "arterial" for precision. The pulmonary arterial system holds blood traveling from the right heart to the lungs; it has a high inert gas tension during decompression. The pulmonary venous system that is carrying blood back to the heart for distribution throughout the rest of the body has the low gas tension that carries over to the systemic arterial system. I taught human anatomy for many years, and prefer the unambiguous description, even if it is rarely employed by others.)

 

[rossh]

Ross,

This is getting silly now.

How much clearer does it need to be made to you?

And in respect to this....

Your end game here is to try to lure ........ < blah blah blah > more implied accusations and derogatory comments.

Simon M

The conversation was between Neal and I. I think Neal can answer his own questions Simon. I'm interested in his opinion - not yours.

We sure as heck don't need more of your deliberate interference to distort, obfuscate, twist context, malicious accusations, etc. (as you have demonstrated once again).

 

[Simon Mitchell]

I'm interested in his opinion - not yours.

Well then, for the record, it seems that Neal's opinion is the same as the opinion you got from me about 20 pages ago:

It is not valid to talk about microbubbles in the bloodsteam as different from microbubbles in any other tissue.

....and since Neal has clarified this point, can I remind you of what you said at various points in this thread:

You cannot judge tissue microbubble growth from VGE presence or volume, and its documented in research this way too. Most in the science community recognize that fact, but a couple want to trick you into making a connection between tissue and venous micro-bubbles. Don't get sucked into the junk science fad

and...

Simon is trying to merge two types of micro-bubbles: tissue micro bubble into venous gas emboli. He wants (needs) to trick you into thinking its the same.

Any comments on that? Is it that Neal is trying to "trick" everyone as well? Or could it be (God forbid).....?

 

[rossh]

I believe this is the common location described in most theory of VGE for seeds to grow, usually described as caveolae in the endothilum. Another description I read is the venous end of capillary beds. Do you agree with that?

Which I believe is different in location of normal DCS microbubble growth, usually described as formation of microbubbles within the tissues themselves. Do you agree with that?

Bubbles form in tissues; blood is just one tissue.
Regarding bubble formation, it is likely a pretty similar process in any tissue.
Efforts to suggest that intravascular bubbles are somehow a completely unique thing does not make sense.

Hi Neal,

I'm afraid these answers are not enough. It's too vague, too easily misread with generic medical terminology and semantics. To say that blood is tissue and bubbles form in tissue, I feel is dodging the questions. These answers implies that all DCS comes from intravascular bubbles (VGE), which is not how the literature describes it.


From Bennett Elliott, 10.4 Pathophysiology of DCS - James, Francis and Mitchell; p535

"Inert gas bubbles in tissue (as opposed to Inert gas bubbles in blood described earlier):
... DCS in other organ systems described below may be due partly or entirely to bubble formation within the tissues themselves.
and continues on to say...
... Tisues that are relatively poorly perfused, and therefore washout gas more slowly, during decompression are most vulnerable to autochthonous bubble formation. Examples include spinal cord white matter, periarticular tissues, adipose tissue, and the inner ear."



The literature states that neurological DCS (spinal, periarticular{joint}, adipose{connective fat tissue}, inner ear) occur in the tissue as autochthonous {in place} extravascular tissue.



Neal, But reading the above, it seems that tissue micro-bubbles that make up various neurological DCS, are not the same as VGE.


Now if some new research has come along that changes all the above, then lets read it please.


*********


My point of all this is preserve the distinction between VGE microbubbles that grow in venous system (intravascular), and regular DCS microbubbles that are documented to grow in the tissue (autochthonous). VGE does not "come from tissue", but does instead grow in blood vessels separately.

Lets not confuse the two, or allow them to thought as, being merged into one same thing.

 

[GLOC]

Or maybe another option:

The original paper that Neal cites is more recent than Bennett & Elliot and things have moved on with more evidence provided...

Aerosp Med Hum Fact 2015 - 2143040
AMBULATION INCREASES DECOMPRESSION SICKNESS IN ALTITUDE EXPOSURE
N.W. Pollock1,2, M.J. Natoli1, S.D. Martina1,2, J. Conkin3, J.H. Wessel III4, M.L. Gernhardt5

or the presentation but no paper from the UHMS meeting...

Regards

 

[npollock]

The description I provided of what is needed to form bubbles is the critical foundation. There needs to be supersaturation and there needs to some nidus from which gas phase (bubbles) can grow. Supersaturation can occur in any tissue that takes up gas during exposure to pressure. Bubbles can form when the pressure decreases below which the gas in solution will stay in solution. That is exactly what is being said in the Bennett and Elliott chapter. The reason many authors focus on discussions of venous gas emboli is not because they are unique in the conditions in which they form, but because we can view them with now commonly available technology. We talk about what we have the most experience with.

The nidus for bubble formation has not been identified - in blood or any other tissue. I use the term "nidus" instead of "micronuclei" since that term has become somewhat conflated in the community. It is accepted as the seed site for bubble formation by the diving science community (essentially a neutral term waiting for a more complete understanding of how the seeding works), but it seems to be less clear in the diving community.

I mentioned that dual frequency ultrasound holds the promise of identifying and sizing bubbles in extravascular tissue. I have appended an abstract from a recent paper by Jay Buckey's Darmouth group below that describes visualizing bubbles in extravascular tissue before (presumably) larger bubbles were identified in vascular tissue (blood). Again, the formation in both is driven by the supersaturation and nidus presence. We have used the Dartmouth box in our lab for a limited number of human trials. It does not yet do the frequency sweeping necessary for sizing, but it can identify really small bubbles (based on the fixed sound frequency it is using).

Swan JG, Wilbur JC, Moodie KL, Kane SA, Knaus DA, Phillips SD, Beach TL, Fellows AM, Magari PJ, Buckey JC. Microbubbles are detected prior to larger bubbles following decompression. J Appl Physiol (1985). 2014 Apr 1;116(7):790-6. doi: 10.1152/japplphysiol.01156.2013. Epub 2014 Jan 16.
Using dual-frequency ultrasound (DFU), microbubbles (<10 ***956;m diameter) have been detected in tissue following decompression. It is not known if these microbubbles are the precursors for B-mode ultrasound-detectable venous gas emboli (bmdVGE). The purpose of this study was to determine if microbubbles could be detected intravascularly postdecompression and to investigate the temporal relationship between microbubbles and larger bmdVGE. Anesthetized swine (n = 15) were exposed to 4.0-4.5 ATA for 2 h, followed by decompression to 0.98 ATA. Microbubble presence and VGE grade were measured using DFU and B-mode ultrasound, respectively, before and for 1 h postdecompression, approximately every 4-5 min. Microbubbles appeared in the bloodstream postdecompression, both in the presence and absence of bmdVGE. In swine without bmdVGE, microbubbles remained elevated for the entire 60-min postdecompression period. In swine with bmdVGE, microbubble signals were detected initially but then returned to baseline. Microbubbles were not detected with the sham dive. Mean bmdVGE grade increased over the length of the postdecompression data collection period. Comparison of the two response curves revealed significant differences at 5 and 10 min postdecompression, indicating that microbubbles preceded bmdVGE. These findings indicate that decompression-induced microbubbles can 1) be detected intravascularly at multiple sites, 2) appear in the presence and absence of bmdVGE, and 3) occur before bmdVGE. This supports the hypothesis that microbubbles precede larger VGE bubbles. Microbubble presence may be an early marker of decompression stress. Since DFU is a low-power ultrasonic method, it may be useful for operational diving applications.

We are also looking for other elements that could be biomarkers of DCS. One of them, microparticles, or small fragments of cells that accumulate in the bloodstream response to stress, hold some promise in possibly being one of the nidus sites, given that the size of the MP changes in response to pressure (implying that it has an associated gas phase - bubble - element). I have attached the abstract from a paper that was released in the last two days. You will see a long list of co-authors. This is a truly international effort to pool resources to find answers. Blood samples from our field dive monitoring studies of technical divers were included.

Thom SR, Bennett M, Banham ND, Chin W, Blake DF, Rosen A, Pollock NW, Madden D, Barak OF, Marroni A, Balestra C, Germonpre P, Pieri M, Cialoni D, Le PJ, Logue C, Lambert D, Hardy KR, Sward D, Yang M, Bhopale VM, Dujic Z. Association of microparticles and neutophil activation with decompression sickness. J Appl Physiol (1985). 2015 Jul 2:jap.00380.2015. doi: 10.1152/japplphysiol.00380.2015. [Epub ahead of print]
Decompression sickness (DCS) is a systemic disorder assumed due to gas bubbles, but additional factors are likely to play a role. Circulating microparticles, vesicular structures with diameters of 0.1 to 1.0 µm, have been implicated but data in human divers has been lacking. We hypothesized that the number of blood-borne annexin V-positive microparticles (MPs) and neutrophil activation assessed as surface myeloperoxidase (MPO) staining would differ between SCUBA divers suffering from DCS versus asymptomatic divers. Blood was analyzed from 280 divers who had been exposed to maximum depths from 7 to 105 meters; 185 were control/asymptomatic divers and 90 were diagnosed with DCS. Elevations of MPs and neutrophil activation occurred in all divers but normalized within 24 hours in those who were asymptomatic. MPs bearing the following proteins: CD66b, CD41, CD31, CD142, CD235 and von Willebrand factor were between 2.4 and 11.7-fold higher in blood from divers with DCS versus asymptomatic divers matched for time of sample acquisition, maximum diving depth and breathing gas. Multiple logistic regression analysis documented significant associations (p<0.001) between DCS and MPs and for neutrophil MPO staining. Effect estimates were not altered by gender, body mass index, use of non-steroidal anti-inflammatory agents or emergency oxygen treatment, and modestly influenced by divers' age, choice of breathing gas during diving, maximum diving depth, and whether repetitive diving had been performed. There were no significant associations between DCS and number of MPs without surface proteins listed above. We conclude that MPs production and neutrophil activation exhibit strong associations with DCS.

I don't share this to say that we have an answer, just that we are actively looking and engaging with many other research groups as we go. We learn a lot as we progress. Some promising avenues turn out to be dead ends, and some continue to be tantalizing. I am pleased to say that most scientists in this field are fine identifying false paths. Everyone would like to find the holy grail, but the important thing is the process. Cogitate, hypothesize, test, revise as needed, repeat. If the research community had any reason to believe the genesis of bubbles was wildly different between blood and non-blood tissue, we would probably have some evidence at this point. We do not.

Speculation is good, but problems develop when you get too married with your ideas. Models are good, as long as you don't ever confuse them with truth. They are predictions. Sometimes they fit, and occasionally even for the reasons you expected..., but not always. It is important to leave room for uncertainty and a revision in thought. I have no problem being proven wrong, but it generally needs to be with sound data or clear justification. I have zero interest in emotional arguments. Feeling strongly about something just does not make it so.

I see a lot of bubbles in decompression studies, in the lab where we control as much as we can, and in the field where we are presented with a much more dynamic range of conditions. I will give answers where I have them, and try to limit my speculation where I do not have them.

 

[GLOC]

Thank you again Neal.

 

[Simon Mitchell]

I'm afraid these answers are not enough. It's too vague, too easily misread with generic medical terminology and semantics. To say that blood is tissue and bubbles form in tissue, I feel is dodging the questions. These answers implies that all DCS comes from intravascular bubbles (VGE), which is not how the literature describes it.

Ross, I am going to try to resolve this issue for you as objectively as I possibly can.

I'm sure that Neal is not trying to imply, and nor am I, that all DCS comes from intravascular bubbles. Indeed, no one has ever said that. Perhaps approaching it in a Q/A format is the best approach for clarity.

1. Q. Is all DCS caused by intravascular bubbles?

A. No.

2. Q. How do we know that?

A. Some forms of DCS have never been associated with right to left shunts. The most obvious example is musculoskeletal pain (the most common single symptom). If musculoskeletal DCS were caused by intravascular bubbles that get carried to the tissue we would expect it to be more common in divers where those intravascular bubbles (VGE) can easily pass into the arteries and then to the tissue (that is, in those divers with a venous to arterial shunt like a PFO). Musculoskeletal DCS is not more common in divers with a PFO and this is strongly suggestive of the fact that it arises from bubbles formed in the involved tissues themselves.

It becomes more complicated for some other forms of DCS (like spinal) where there is an association with right to left shunts, but where there is also evidence that tissue bubbles can also be involved. You can find a classic exposition of this in my Bennett and Elliott chapter that you cite. We described James Francis's work which actually demonstrated bubble formation in spinal cord white matter. This combination of bubbles being found in the spinal tissue AND an association of spinal DCS with right to left shunts suggests that the spinal cord can be damaged by both mechanisms: bubbles forming in the tissues, and VGE crossing a right to left shunt and embolising the spinal circulation.

Q. Is some DCS caused by intravascular bubbles?

A. Yes.

Q. How do we know that?

A. There is a variety of evidence we can cite here.

First, there is the correlation of VGE numbers against risk of DCS. I am not going to elaborate on that further here, and I have cited the data a few pages back. I agree the correlation is not precise (and this may be because - as I point out above - some forms, including very common ones, are probably not caused by intravascular bubbles. I'm sure you can understand that this would weaken any attempt to correlate VGE against cases of DCS.

Second, there is the strong association of several forms of DCS (inner ear, skin, spinal, cerebral) with right to left shunts. As I allude to above, the only really plausible explanation for such an association is that VGE are crossing the right to left shunts and being "delivered" to these organs in the arterial system. The reasons for their particular vulnerability to this are discussed elsewhere, such as:

MITCHELL SJ, DOOLETTE DJ. Pathophysiology of inner ear decompression sickness: potential role of the persistent foramen ovale. Diving Hyperbaric Med 45, 105-110, 2015

I am happy to send this to you or anyone else who is interested.

As I point out above in relation to spinal DCS, it is possible that some of these organs (with the probable exception of the brain) can also be injured by bubbles forming within the tissue itself (and this has to some extent been demonstrated in respect of inner ear DCS as you cite from my chapter). Nevertheless, the fact remains that this association with right to left shunt remains, and this implicates intravascular bubbles. The reason you cannot dismiss this as an anomaly of 'defective circulation' is that many people in the diving population have PFOs and we don't routinely screen for them. Even if we did, there would still be the problem of VGE crossing pulmonary shunts which can happen in most people under the right circumstances.

Q. Can we view VGE as completely independent of tissue bubbles?

A. No.

Q. Why?

A. VGE arise from supersaturated gas that the blood acquires from tissues. The more supersaturated the tissues, then the more supersaturated the blood passing through tissue capillaries will become, and the more supersaturated the capillary blood, the more bubbles that are likely to appear in the venous blood downstream of the tissue. Thus, VGE numbers are inextricably linked to the supersaturation state of the tissues, and therefore to the propensity for bubbles to form within the tissues themselves. Put another way, VGE numbers provide an index of the whole body tissue supersaturation state, with more VGE reflecting greater tissue supersaturation in the places where the VGE arise. Logically, more VGE reflects greater tissue supersaturation and greater tendency for tissue bubbles to form.

My point of all this is preserve the distinction between VGE microbubbles that grow in venous system (intravascular), and regular DCS microbubbles that are documented to grow in the tissue (autochthonous). VGE does not "come from tissue", but does instead grow in blood vessels separately.

For the reasons I articulate above, we can neither assume that DCS arises because of tissue bubbles, nor is it correct to say that VGE are unlinked to tissue supersaturation (or that they don't "come from tissue" as you put it). VGE are directly linked to tissue supersaturation because that is where the gas within them comes from.

Lets not confuse the two, or allow them to thought as, being merged into one same thing.

No one is confusing them, or merging them, but they are all part of the same process.

Simon M