Can apnea cause brain damage?

[trux]

I just posted a message about a new study documenting a case of meningitis associated with freediving (http://forums.deeperblue.com/freediving-science/88755-another-freediving-risk-meningitis.html), and I wonder whether the increased permeability of the blood-brain barrier at long breath-holds as reported in Jonas' study could not have contributed too to the infection.

If Jonas (or another expert) peeks in, could you tell us whether the release of S100B you measured, means that the blood-brain barrier remains weaker for certain time after the apnea, or is it just an immediate effect, and the levels of S100B measured later are just residuals? If the barrier is weaker, is the brain more vulnerable to viruses, infections, or drugs? Or is there no relation?

 

[Rik]

The original article (Pollara 2010) mentions an ear infection as cause of the meningitis, with a direct route through the mastoid bone on both sides of the skull. The pathogen was probably introduced with water during equalization.

So, in this specific case, no blood-brain barrier was probably involved. Neither is blood a normal transmission route in immunocompetent adults for this specific strain of bacteria. Nevertheless, based on this case-report, you might want to advice against using sea-water to fill air cavities in the skull.

To my knowledge, the relation between S100B and the blood-brain barriere damage is still hypothetical, and an recent article suggested against the relation between blood-brain barrier integrity and an increased or decreased S100B level. (Kleindienst et al. The Passage of S100B from Brain to Blood Is Not Specifically Related to the Blood-Brain Barrier Integrity)

 

[neurodoc]

This is a fascinating and interesting thread. It's unfortunate the media chooses to run with inaccurate stories for the sake of selling their product.
One thing that has not come up at all during this discussion is:

1. What are the differences between people that make one more vulnerable to hypoxic brain damage than another?

2. What are some real-world things that can be done to minimize the damage in ourselves as we continue to practice apnea?

(I'm sitting in a functional neurology seminar as I read this thread and type this...perfect timing.)

Some thoughts to hopefully trigger this adjunct to the conversation:
Vulnerability to damage is a direct result of the functional state of one's brain at the time of hypoxia. This means many different factors can be considered:
presence of pro-inflammatory metabolites and substances in the brain and nervous system, how functional and how balanced is the autonomic nervous system (ie how quickly can vasoconstriction reverse to normal, what is the blood perfusion to brain areas while at rest, how many areas are functional but unhealthy?) What is the status of other aspects of health-insulin levels, blood glucose levels? High insulin levels compromise BBB, promote inflammatory changes in brain. How healthy is the person's diet? this can affect susceptibility to inflammatory/neurodegenerative cascades with tragic end-points. Does the person have any problems developing in the lining of the intestines, which causes "leaky gut syndrome" which causes inflammatory changes and promotion of a weaker BBB and hence auto-immune inflammation once more...
Sensitivity to gluten as trigger for neuroinflammation/neurotoxicity is becoming more a topic of conversation in my field. These are all variables of which much is known.
Eric F, you have touched on some nutritional recommendations that fall in-line with these thoughts as well, and I enjoy reading your posts.
Some foods produce more inflammatory by-products such as arachidonic acid and leukotrienes. An anti-inflammatory diet is healthier but specifically will make brain damage less likely from occasional hypoxia. Some spices, such as tumeric, circumen, curry, ginger have been shown in research to reduce inflammation. These can perhaps reduce some of the inflammation that is part of the brain-injury cascade of events. Also, 3 or 4 grams/day of Omega 3 fatty acids is very protective. Simple things like eating grass-fed beef instead of grain-fed beef (huge difference in Omega 3/Omega 6 ratios found in Australian studies).
There is soooo much that could be studied here! my point is that in the meantime, there is much we can do to potentially reduce our own tendency to have problems, without giving up our sport.
Sorry about the long post! hope that contributes something to the conversation. Thanks!
Richard

 

[podge]

Ok then Richard I was right there with you for the first part of your post “This is a fascinating and interesting thread”
After that it’s all Dutch to me baby!
Just kidding Sir, great reply and you’re a first class addition to the Deeper Blue Clan.
Rep sent.

 

[Johan Andersson]

There is a new publication slightly associated with the topic of this thread.

Breath hold diving: In vivo model of the brain sur... [Med Hypotheses. 2011] - PubMed result

I have not read the full paper yet, but does not contain new findings or observations, as far as I have seen. It is putting forward the hypothesis that "adaptations to extended cessation of breathing ending with extreme hypoxia can be used as a model of brain survival response during conditions involving profound brain deoxygenation and in some instances reduced brain perfusion".

/Johan

 

[JWP]

Quick q to johan: What sort of oxygen saturation levels are seen in people who go to high altitude with acclimatizing well? Also, what sort of % O2 is typical for around a 5 minute breath hold.

 

[Johan Andersson]

JWP, of course this varies with altitude. Roughly, the following are SaO2 values at different altitudes. But remember that SaO2 is only one part of it. With a higher Hb at altitude, a certain level of saturation means a larger vol% of O2 in the blood at the same saturation (compared to at sea level).

2500 m: 90%
4600 m: 75%
6100 m: 65%
7300 m: 50%
8848 m: 70% (estimated from data from one subject)

The estimated SaO2 is higher at 8848 m than at 7300 m owing to a severe alkalosis and a left shift of the hemoglobin dissociation curve following hyperventilation at "max altitude".

In our study (reported in the beginning of this thread), the average SaO2 (determined by blood gas measurements, not pulse oximetry) at the end of 5.5 min apneas (average) was 54%.

/Johan

 

[trux]

The estimated SaO2 is higher at 8848 m than at 7300 m owing to a severe alkalosis and a left shift of the hemoglobin dissociation curve following hyperventilation at "max altitude".

Does it mean there is no vasoconstriction of carotides after the severe alkalosis / hyperventilation at that altitude like it is the case normally?

 

[Johan Andersson]

Does it mean there is no vasoconstriction of carotides after the severe alkalosis / hyperventilation at that altitude like it is the case normally?

I can't answer you with certainty on that one. I guess there could be some vasoconstriction of cerebral blood vessels due to low CO2 levels. The body is certainly not perfectly adapted to those altitude exposures and sometimes the responses that are elicited are actually counterproductive (there are several such examples). In this case, a cerebral vasoconstriction due to hyperventilation would potentially reduce the cerebral oxygenation. On the other hand, there may be some physiological adaptation that reduces the cerebral vasculature's responsiveness to hypocapnia. I'm not sure about that.

(On a side note, is it really the carotid arteries that would be affected? I would say it's further up in the cerebral vasculature that you would see the effect - vasoconstriction - from hypocapnia. But, I'm not 100% sure that it is "only" the cerebral vessels, and not the carotid arteries, that are affected.)

/Johan

 

[trux]

Indeed it is quite interesting, and it is a pity it was not studied closer. I asked because it surprised me that the SaO2 was 70% at 8848m, while only 50% at 7300m, and that you told it was thanks to the hyperventilation, while at normobaric conditions the hyperventilation has the exactly opposite effect on the cerebral flow.

I guess you are right about the cerebral arteries (finally it is you who is the expert here ), but diverse sources often speak about the vasoconstriction of carotides at hyperventilation. It is certainly true that the other cerebral vessels contract too, but since the blood gets into the brain through the carotides anyway, the simplification does not sound too bad.

 

[Johan Andersson]

Indeed it is quite interesting, and it is a pity it was not studied closer. I asked because it surprised me that the SaO2 was 70% at 8848m, while only 50% at 7300m, and that you told it was thanks to the hyperventilation, while at normobaric conditions the hyperventilation has the exactly opposite effect on the cerebral flow.

Please note that these were estimates based on one subject (and not my own observation). But at the same time, increasing the SaO2 (the arterial hemoglobin O2 saturation) doesn't necessarily mean that the brain is receiving that much more oxygen if this increase in SaO2 is offset by cerebral vasoconstriction. I didn't mention anything about opposite effects from hyperventilation at altitude, did I? At least, I did not mean anything like that.

/Johan

 

[trux]

I didn't mention anything about opposite effects from hyperventilation at altitude, did I? At least, I did not mean anything like that.

No, of course you did not, but the numbers did the job. If the SaO2 steeply drops with the altitude, but then miraculously shoots up 20% at the peak of the Mt. Everest, and it is contributed to the severe hyperventilation, then to my ears it sounds like the opposite of what we observe at people hyperventilating in normal conditions - they often black out, just because of the low cerebral O2. Please note that I do not put in doubts the results at all, and please do not take my comments for critics. It is exactly the opposite - I am very thankful for the interesting data. I am just wondering how it happened, and trying to understand why the hyperventilation did not aggravate the cerebral hypoxemia.

Or do you believe that the estimate of 70% might have been completely wrong, and that in fact the subject had SaO2 lower than at 7300m (which is what I would expect)? And why he did not hyperventilate at 7300m, if it was helping so greatly at 8800m? Or did something change in his altitude adaptation between 7300m and 8848m?

 

[Johan Andersson]

...it sounds like the opposite of what we observe at people hyperventilating in normal conditions - they often black out, just because of the low cerebral O2.

Do you mean blackout following hyperventilation before an apnea is even begun, or do you refer to the increased risk of blackout at the end of an apnea preceded by hyperventilation? The two are caused by different things.

1) You can hyperventilate to blackout without apnea. But that would not be related to low cerebral O2 levels. That would rather be a consequence of respiratory alkalosis (high blood pH) following excessive elimination of CO2. The high blood pH reduces ionized calcium concentration in the blood. The low concentration of ionized calcium in turn is what is disrupting normal neural functioning/signaling, leading to the blackout.

2) If you refer to blackout at the end of an apnea preceded by hyperventilation, I know you are familiar with the mechanisms involved. This is caused by low O2 levels. A relative hypocapnia caused by hyperventilation leading to a reduced cerebral blood flow as well as the higher affinity of hemoglobin for O2 with hypocapnia will reduce the O2 delivery to the brain, causing blackout.

People at high altitude would potentially be affected by both mechanisms at the same time. The difference is that the physiological strain develops over a longer time (hours to days) when you climb a mountain compared to when you suddenly begin to hyperventilate or hold your breath (a matter of minutes in conditions 1 and 2 above), which means that the adaptations and responses may be quite different (even though you will never be adapted to such an extent that you will not be severely affected by a visit to the altitudes we are discussing). But there are so much more going on in the body in the case of altitude exposure so that direct comparisons to hyperventilation and apnea-induced hypoxia are tricky. For instance, the body's CO2-buffering systems are affected by altitude, because the hypoxia-induced increase in ventilation leads to "chronic" hypocapnia.

/Johan

 

[trux]

What I meant was neither really 1 nor 2, but especially the hyperventilation induced cerebral vasoconstriction. Both the cerebral vasoconstriction and cerebral blood desaturation after hyperventilation are well documented in the scientific literature. Well, I am also aware that the vasoconstrictive effect slowly diminishes and returns to normal at prolonged hyperventilation (documented for exemple in http://www.nil.wustl.edu/labs/raich...od Flow During and After Hyperventilation.pdf), but I still do not understand the sudden and huge increase of SaO2 attributed to hyperventilation at the extreme altitude. I've put the data into a graph to demonstrate how much paradoxal the result is:

​

 

[Johan Andersson]

but I still do not understand the sudden and huge increase of SaO2 attributed to hyperventilation at the extreme altitude

OK, so let's just focus on this (ignoring any effect from hyperventilation on cerebral blood flow). I do not believe that it should only be attributed to the hyperventilation, but that what was written in the source from where I collected the values (High Altitude Medicine, H. Hultgren, 1997).

At 7300 m the inspired (ambient air) PO2 was 52 mmHg, arterial PO2 was 34 mmHg, arterial PCO2 was 16 mmHg, and SaO2 was 50%.

The values from 8848 m were from a separate study. I'm not sure, but I think it was a higher barometric pressure at the day of that study (even though it is not mentioned as an explanation), which would have contributed to a higher inspired PO2 and consequently SaO2. Anyway, as reported, at 8848 m the inspired PO2 was 43 mmHg (9 mmHg lower), arterial PO2 was 28 mmHg (less O2 in inspired air gives lower PaO2, but the reduction is "only" 6 mmHg due to the hyperventilation), arterial PCO2 was 7.5 mmHg (due to hypoxia-induced hyperventilation), and SaO2 was 70%. But there are uncertainties for several reasons (just one subject, arterial PCO2 were obtained by extrapolation from venous blood samples drawn hours later at a lower altitide, etc.)

Nevertheless, at these arterial PO2s, we are at the step portion of the Hb-O2 dissociation curve (which shows you the relationship between PaO2 and SaO2). Thus a left shift of the curve (the Bohr effect) due to low CO2 will have a dramatic effect on SaO2. There will be a higher SaO2 at the same PaO2 (and even possibly a higher SaO2 with sligtly lower PaO2 as in the case of 7300 vs 8848 m). At the same time, the unloading of O2 from hemoglobin to the tissue will be impaired (higher affinity of Hb for O2), so it's not only beneficial.

I wouldn't say that I am convinced that the 70% SaO2-value at 8848 m is correct (neither can I dismiss it with certainty), but it would not surprise me if SaO2 could be higher at 8848 m than at somewhat lower altitudes, for the reasons explained above. But 20% higher...? I'm not sure...

Finally, I guess the reason for JWP to initiate the discussion about altitude was to see if it would be possible to compare altitude exposure to apnea. Well, there are some similarities, but also huge differences.

/Johan

 

[trux]

Johan, let me summarize it: on one side we have a study with relatively consistent data from multiple subjects, showing a clear declining SaO2/altitude curve. When we ignore any other factors and extrapolate it very conservatively (connecting the starting and the ending point linearly), we get the SaO2 of some 30% for the 8848m. In fact the curve would rather deserve inverted exponential extrapolation, where we would get values in the range of 10%-20%.

Now, on the other side we have:
- an unrelated study,
- with only one subject where we do not know the level of his altitude adaptation in comparison to subjects from the other study
- we do not know what was the atmospheric pressure in comparison to the other study, hence we do not know the inspired PaO2
- we do not know what the SaO2 was at 7300m in the second study. Or is that data available, and the SaO2 was identical (50%) too?
- the SaO2 was measured hours later (!!!) at lower altitude (!!!)

Can such estimation really be taken seriously, and does it authorize us to draw the conclusion that the saturation was really 70%, hence not 20% above the estimation, but in fact 40%-60% above it? Do we know that the saturation of the subject in the second study at 7300m prior the ascent was not much higher than at subjects from the first study? Do we know whether the estimation based on a measurement done hours later and at lower altitude is not simply way off, because the subject recovered faster than expected on the descent?

I understand that if the SaO2 really rose from 50% @ 7300m to 70% at 8848m (instead of to the extrapolated 10%-30%), then it must be because of a very strong left shift of the dissociation curve. The only other explanations could be wrong data, or that the subject breathed oxygen. Now, even if we ignore the strong effect of such extreme hyperventilation on the vasoconstriction of cerebral arteries, there is still the strong Bohr effect that renders the oxygen bound to hemoglobin quite difficult to unload, and hence to great extent unusable. The hypoxic tolerance would drop significantly.

I can imagine that with hyperventilation the organism could slow down or stop the decline of the SaO2, but wonder whether it could bring it up from 10%-30% to 70% without causing critical cerebral hypoxemia due to the strong Bohr effect (and perhaps also due to cerebral vasoconstriction).

So this is why I am telling I do not understand it, and wanted to know whether there is some other mechanism involved that I do not know yet.

 

[Johan Andersson]

We keep drifting away from the original topic of this thread...

When we ignore any other factors and extrapolate it very conservatively

But I would say you can't do that. You can adapt to lower altitudes, and that's partially why you have the nice association between altitude and SaO2 that you presented in the graph you provided. But you cannot adapt to 8848 m. Therefore, you cannot extrapolate because there will be acute physiological responses (for instance vigurouos hyperventilation) that will "obscure" the extrapolation. And because we are at the step section of the Hb-O2 dissociation curve, this can lead to large changes in saturation (not only a beneficial increase because it will also be more difficult to unload O2 from the hemoglobin, as both you and I wrote before). Consequently, I do not think it is reasonable to use measurements from lower altitudes and extrapolate to 8848 m and say that the SaO2 "should be" 10-30%, because the acute exposure to this altitude changes physiological responses.

Now, on the other side we have:
- an unrelated study,
- with only one subject where we do not know the level of his altitude adaptation in comparison to subjects from the other study
- we do not know what was the atmospheric pressure in comparison to the other study, hence we do not know the inspired PaO2
- we do not know what the SaO2 was at 7300m in the second study. Or is that data available, and the SaO2 was identical (50%) too?
- the SaO2 was measured hours later (!!!) at lower altitude (!!!)

Partially right, but also some points I want to comment.
- Yes, it is an unrelated study.
- Agree on this too. I have not looked in the original publication for that.
- Actually, we know the inspired PO2. I gave these values in my previous post (7300 m: PiO2 52 mmHg; 8848 m: PiO2 43 mmHg).
- These values may be available. I have not looked in the original publication for that.
- The SaO2 was not measured hours later, it was the PaCO2.

Can such estimation really be taken seriously, and does it authorize us to draw the conclusion that the saturation was really 70%, hence not 20% above the estimation, but in fact 40%-60% above it?

As I wrote above, I don't think you can make the direct extrapolation that you were doing. A SaO2 of 10-30% would not be compatible with the physical activity needed to climb the peak. It is simply not possible. And the saturation, according to the source I read, was not estimated but measured at 8848 m. But again, I wouldn't say that I am convinced that the 70% SaO2-value at 8848 m is correct, and I will not try to explain it or defend it any further. I hope I have already explained it to the best of my knowledge above. I don't think I have anything else to add on that particular value.

Now, even if we ignore the strong effect of such extreme hyperventilation on the vasoconstriction of cerebral arteries, there is still the strong Bohr effect that renders the oxygen bound to hemoglobin quite difficult to unload, and hence to great extent unusable.The hypoxic tolerance would drop significantly.

I can imagine that with hyperventilation the organism could slow down or stop the decline of the SaO2, but wonder whether it could bring it up from 10%-30% to 70% without causing critical cerebral hypoxemia due to the strong Bohr effect (and perhaps also due to cerebral vasoconstriction.

Yes, in general I agree (except for some hesitation about the extrapolation of SaO2 to 10-30% ). And the reasons you give are some reasons why we can't go much higher. A peak of 10000 m (and thus lower PiO2) would not be climbed without supplementary oxygen. In fact, even the reduction of barometric pressure of only 10 mmHg, such as occurs between summer and winter on the Everest summit, reduces the oxygen uptake to such an extent that that the mountain cannot be climbed. This is presumably one reason why the mountain has not yet been climbed in midwinter without supplementary oxygen.

/Johan