KristoriaBlack wrote:So to summarize, acclimatization involves many changes (some biochemical) and is correlated with an increased hematocrit, in this case an increase in the hematocrit is good for the climber. While CMS is also correlated with an increased hematocrit and in the context of CMS it is bad for the climber. See the problem?
On the other hand this line of reasoning might be totally wrong. One should note that a correlation does not equal causation. Has anyone actually tested whether the increase in hematocrit is good for the climber's short term adaptation to high altitude? It does not matter what is intuitive, it is only cold, hard experimental data that is to be believed. If the increase in hematocrit is so good for the acclimatization process then why are we encouraged to drink water to prevent dehydration? We know that drinking water is good for acclimatization, but would that not just decrease the hematocrit by diluting the blood? (It may just be me that doesn't get it. )
So who knows. Assuming that a HIF inhibitor would work for AMS, would a HIF inhibitor work time wise? The answer again is who knows?
Christine -- first, thanks for the offer of the article. I would like to read it, and will bug you in a few weeks for a copy if that's okay.
I did a little digging on AMS and reach the same conclusion -- we know what causes AMS (rapid ascent to higher altitudes), but we don't have a very good handle on why. Without knowing the mechanism(s) by which AMS strikes, I don't see how specific treatments or preventative measures can be developed. And, I don't see how the study on Tibetans can (yet) be related to AMS. I didn't find any studies on whether an increase in hematocrit is helpful in the short-term to acclimatization (I agree that would be interesting).
I don't get it either, but it's a cool subject. Thanks for the thoughts.
cb294 wrote:
Commenting as a geneticist / developmental biologist (not a physiologist, so count that for what it is worth) I´d doubt that the dehydration induced increase in hematocrit is helpful in acclimatization and avoidance of AMS. If anything, reduced capillary flow should negatively affect total transport capacity.
The slow, Epo mediated increase in total erythrocytes at more or less normal density will eventually increase oxygen carrying capacity, but that takes several days to weeks (unlike the fast pH response).
So even if modulating HIF/PPARa activity could well have an affect on AMS, it would probably be by one of the ten thousand other targets of HIF, but unlikely by targetting Epo mediated erythrogenesis.
Anyway, I´d love to see is what the oxygen carrying capacity of Tibetans actually is (higher despite lower or equal hematocrit?), and even more, whether the mutations suppressing the HIF response (avoiding CMS caused by chronically increased hematocrit but sacificing some oxygen carrying capacity) are balanced by other mechanisms that upregulate oxygen transfer to the target organs. In the end you don´t really care how much oxygen you have in your blood but about the levels in your brain and muscles.
Your comments on the timeliness (or lack thereof) of the Epo mediated increase in total erythrocytes confirm what I found by cruising some articles on the web. Too slow a reaction to stave off AMS (yes?). So, it would make sense that if modulating HIF actually worked with respect to AMS, it would be by some other unknown pathway.
I also would like to see more studies on the Tibetan population -- both genetic and with respect to oxygen carrying capacity. These studies appear to hold the key to CMS, and maybe will open some doors with respect to AMS.
Thanks -- you and Christine gave some good insight into this question (I get to go along for the ride as the untrained straightman).
Rick