Tech Diving Journal Club – The at-depth endothelial dysfunction hypothesis

A diving friend recently pointed me to an interesting paper which had appeared in 2009 in the journal Medical Hypotheses, titled Gas bubbles may not be the underlying cause of decompression illness – The at-depth endothelial dysfunction hypothesis by Leigh A. Madden Gerard Laden. You can download the full text version from Academia.edu here.

I’d like to discuss what I think about the rather unusual suggestions in the paper. As usual, good information or at least interesting thoughts are buried in scientific-medical jargon, which is a shame. It keeps otherwise well-educated and intelligent folks, who simply lack the specialized training in parsing that lingo, from grasping the content of the paper. Maybe that’s where I can help.

The first thing to mention is that Medical Hypotheses is an interesting journal. In today’s academic world, things are often pretty restricted and it’s not that easy to just put a daring and unusual hypothesis out there. In most journals, the referees will be very strict when someone suggests a new interpretation of the facts, or a new hypothesis, without super-solid factual support. This is good, on the one hand, since it “keeps science real”, but it also might impede the discussion of interesting, but more speculative ideas. This is where Medical Hypotheses comes in: in this journal the ideas must be scientific (no UFOs or gremlins can be discussed), but the hypotheses can be very unconventional. This had led to some awkwaaaaard moments in the past, when someone published AIDS denialism in the journal,but mostly the journal’s policy has led to interesting contributions…

What do Madden & Laden suggest? They observe that the presence of bubbles does not correlate one to one with the occurrence of decompression illness (DCI). They cite a study from the 1990s which shows high bubble counts in divers with no DCI (who ascended after very long, shallow dives) and also state that case are documented where DCI happened despite no suspicious bubble elevation.

I think the case for a bubbles  DCI relationship is not as weak as they make it sound, but the correspondence is not completely clear. Also, while gas-compartment based decompression models include some gas diffusion physics, they do not include a lot of other physics and physiology, and we can ask if they are indeed mechanistic models, or simply fits to data (which mostly work!)

So, what do the authors then suggest as an alternative model? Basically, they think that high pressure, and hence high oxygen partial pressures, mess up the blood chemistry involved in inflammation, blood clotting and blood vessel constriction. Bubbles, so they argue, cause secondary damage only. Then comes a discussion of the biological molecules involved in oxydative stress, including some cell adhesion molecules and NO, an important regulator of blood vessel volume.

I think the idea that tissue stress due to high oxygen partial pressure contributes to DCI is interesting. But I don’t see how it can be the primary cause? Breathing oxygen at the surface, or at 6 meters, without having exposed yourself to a regiment which causes bubbles, does not cause DCI, does it? Prolonged exposure to pure O2 can irritate the lungs, but it can’t cause the typical symptoms of DCI, right? And indeed, next the authors are somewhat departing from their original claim that the bubbles are only secondary, and state: “To focus on oxidant status and its effect on the endothelium; gas bubbles may form at the endothelial surface where conditions are thought favourable through mathematical modelling.”

This sounds more like the hypothesis that a stressed endothelium (due to high oxygen pressures) is more likely to provide a substrate for new bubbles. That’s a more conventional idea, which seems more consistent with known causes of DCI. And it makes sense to me.

The authors also discuss how anti-oxydants like vitamin C could reduce oxydative stress in tissues; This could pave the way for a scuba diving supplement reducing the chances of getting DCI.

I have had a similar idea a while ago: A diving supplement, based on properly hydrating and reducing oxydative stress. I was thinking more in terms of oxygen toxicty when aiming to reduce O2 toxicity via taurine, but possibly it can affect DCI as well. It didn’t find all that much resonance, and was met with the suggestion that “most divers prefer to drink beer anyway, and not some supplement”. Fair enough. Maybe with a real chance of reducing the likelyhood of DCI such a supplement will catch on after all. Probably most divers will stick to beer, though.