Hello Rob,
As my colleague (rsingler) has pointed out you have to be careful about things published in "Medical Hypotheses". This is a journal dedicated to the promulgation of blue sky ideas that have some sort of provenance in logic, but don't need to be proven. In the case of the "at risk endothelium hypothesis", I think the journal's usual leniency was pushed beyond the limit. Consider the pivotal statement you cited:
"Breathing higher partial pressure of oxygen, when diving results in an increase in arterial oxygen tension, which in turn causes an oxidative stress related vasoconstriction. This can lead to increases in shear flow and vascular remodelling in the form of increased adhesion molecule expression and release of microparticles".
As a cause of decompression sickness, this hypothesis has a hole so large you could drive a Mack Truck though it. Specifically, every day, all over the world, thousands of patients undergo hyperbaric oxygen therapy during which they are exposed to far higher doses of oxygen than divers are. If oxygen exposure and oxidative stress (rather than inert gas bubbles) were the cause of decompression sickness, then we would expect it to be a common event among patients treated with hyperbaric oxygen.... but I don't believe there has been a single case of DCS, EVER, in millions of hyperbaric oxygen treatments.
Having said that, there is current interest and research on one entity mentioned in the hypothesis: so-called microparticles. For the reasons mentioned above, exposure to high oxygen levels alone is probably not the pivotal cause for their generation, but they do appear after diving (see below) and they are potential vectors of injury in DCS; not to the exclusion of bubbles as co-vectors, but most likely in addition to bubbles.
Microparticles are tiny fragments of the cell walls of blood constituents (like red cells, white cells and platelets) and endothelium (the cells lining blood vessel walls). They are present in our blood all the time, but are elevated in many disease states. They are known to have pro-inflammatory effects, and could thus contribute to blood vessel and tissue injury in those diseases where they are elevated. They have been shown to be elevated after dives, and are often elevated even more in divers diagnosed with DCS. However, the relationship between microparticle numbers and DCS is a little like venous gas emboli (VGE) and DCS. It is inconsistent and certainly not a clear cut correlation.
Anyway, the presence of elevated microparticles in the blood after diving and in DCS has raised interest in whether they have a role in producing DCS symptoms. All possibilities are still open at this time. They could merely be an epiphenomenon or marker of tissue harm DCS with no real active role in causation, or alternatively, they could exert pro-inflammatory effects that contribute meaningfully to the symptom picture. We don`t know for sure at this stage.
There is also great interest in what causes the microparticle elevations in diving. One obvious hypothesis is that it is microbubble formation that damages the parent cells creating the microparticles. If this were so, we might expect to see close correlations between microparticle numbers and bubble grades after diving... but there is conflict between studies on this issue. One possible reason for this inconsistency (and it gets even more complicated here) is that some microparticles contain tiny amounts of gas, and they may actually act as micronuclei for bubble formation. In that scenario, as bubble numbers increased microparticles would be consumed and their numbers would fall.
Contrary to the title of this thread, there is no popular belief or even strong suspicion that microparticles are the sole cause of DCS and that bubbles have no role. There are a number of compelling reasons for saying this.
First, microparticle elevations to levels as high or higher than seen in DCS are seen in other disease states (like sepsis), and yet we don`t see symptoms of DCS in those non-diving patients.
Second, some of the harm caused in certain forms of DCS (particularly spinal DCS) has been reasonably clearly attributable to bubbles in animal studies.
Third, if DCS was caused solely by a circulating pro-inflammatory agent like microparticles, we would expect sensitive and functionally important tissue that receive high blood flow (and therefore large numbers of microparticles) like the brain, liver and kidneys to be particularly vulnerable to injury. Although the brain is sometimes involved in DCS the liver and kidneys almost never are. Indeed, the tissues that appear particularly susceptible to injury by a circulating agent (such as inner ear, spinal cord, skin) are those that wash inert gas out more slowly; that is, they have inert gas kinetic profiles that suggest that damage is caused by bubbles arriving in the arterial blood shortly after surfacing, impacting in the tissue capillaries, and growing as supersaturated inert gas remaining in the tissue diffuses into them.
Finally, the most common symptom of DCS (musculoskeletal pain) has never been linked to a circulating agent and is most likely to be caused by formation of bubbles in the local pain sensitive tissues.
The role of inflammatory processes (like microparticles) in DCS, either incited by bubbles or by some independent mechanism is of great interest to the field at the present time. The prevalent belief is that bubble formation is the primary event that makes DCS different to the other conditions in which microparticles are elevated, but many of us also suspect that microparticles have a role to play in the inflammatory amplification of the injury. There would be few (if any) diving physicians who do not think bubbles are important.
Simon M