Orthostatic intolerance

Here then is a basic question: if we do not know if this severe problem is immune or autonomic control driven, why can we not find out? Is it that at this point there are no possibilities for distinguishing, or is it that the work has not been done?


These things are not as easy as they might seem. The process might involve both immune and autonomic steps and there are half a dozen different autonomic aspects that might be involved.

I set ou in 1973 to work out why joints were swollen rheumatoid arthritis. I finally came to think I knew enough of the answer to devise a treatment in 1996. And I was able to make use of data from lots of other research groups. The problem for ME I think is that it has been ignored and the few people who have studied mechanisms may not always have been familiar with the complexity of the physiology. Hopefully people like David Systrom can now make some real progress.
 
These things are not as easy as they might seem. The process might involve both immune and autonomic steps and there are half a dozen different autonomic aspects that might be involved.

I set ou in 1973 to work out why joints were swollen rheumatoid arthritis. I finally came to think I knew enough of the answer to devise a treatment in 1996. And I was able to make use of data from lots of other research groups. The problem for ME I think is that it has been ignored and the few people who have studied mechanisms may not always have been familiar with the complexity of the physiology. Hopefully people like David Systrom can now make some real progress.
Yes, indeed. The tragedy for the suffering is that Dr Systrom is totally new to this illness. And it will take him some time to learn it. And doing this mestinon trial is not encouraging, because it is money wasted when the other issues highlighted need urgent attention.
 
Mild OI is hard to describe: just a vague sensation of feeling unwell and being unable to connect to other people, having embarassing difficulty paying attention or doing mental tasks (that include conversation). A bit drifting away from the present and being unable to shake it off.

OI can also be caused by sitting on a chair, it will just take longer and produce milder symptoms.

At least that is what I think is happening.
I agree completely. If I sit up for extended time, my HR can exceed 100 in that position. I just felt tired and did not realize what was happening until I started wearing a HR monitor.
 
Newton thought that fatigue was due to low cardiac filling pressure. What I think needs to be considered is that things may be the other way around.

People with ME feel terrible. If you feel terrible you lie down. If you lie down enough several control mechanisms that maintain cardiac filling pressure on standing become less efficient. There are at least three - resting plasma volume control, peripheral venoconstriction through autonomic nerves and oncotic pressure control through albumin levels. All of these are known to become less efficient if you spend a lot of time recumbent.
I'm confused - doesn't deconditioning lead to high filling pressures?

I thought a key take-away from Systrom's POTS work in 2016 was: cardiac mass was reduced but low filling pressures were found in POTS iCPET - opposite to expectations in deconditioning.
 
I'm confused - doesn't deconditioning lead to high filling pressures?

Deconditioning might lead to a higher filling pressure if the heart fails to keep up with venous return pumped by active muscles. (This might only be true if the heart is more deconditioned than peripheral muscle.)

But lying down is likely to lead to lower filling pressures when exercising upright because of changes that will blunt the mechanisms that crank up filling pressure when shifting from lying down to standing.
 
So the POTS patients studied must have occupied an awkward middle ground of lying down long enough for mechanisms to effect their venous return but not long enough to cause deconditioning of the heart muscle? This seems like a bit of a narrow window to me.
 
This seems like a bit of a narrow window to me.

Maybe not. To get raised filling pressure with cardiac deconditioning you would need that to be quite significant - i.e. raised filling pressure is more or less the definition of heart failure. You should need a mismatch from peripheral muscle capacity. In other words you may need there to be something specifically wrong with the heart. I suspect there are lots of people, who would count was normal on the test, who are as inactive as PWME and are to the same degree 'deconditioned' but who do not deliberately lie down a lot of the time to avoid ME symptoms.

After all, the evidence we have seems to suggest that PWME are not particularly reconditioned but we do know they prefer to lie down.
 
Is reconditioning an option then? I could do with a reconditioned body, as long as it was cheap, and had a lifetime warranty ;)
I think like with mobile phones I would steer clear of anything that someone else had previously used and taken into the toilet ...unless it was sterilised ...however the thought of it is still gross. I think I would prefer a brand new body grown in a lab

NB: I would imagine retorting a human would hamper it’s functionality somewhat?...perhaps UV irradiation?
 
@Jonathan Edwards . Neil McGregor mentions increased protein catabolism. Could this affect cardiac muscle and lead to " small heart"?

I don't see that it would lead to small heart volumes. It might lead to a thin heart wall I suppose, but I am a bit sceptical about increased catabolism as an ongoing state in ME. People would waste away to nothing over years. I have not heard about this idea from McGregor.
 
These things are not as easy as they might seem. The process might involve both immune and autonomic steps and there are half a dozen different autonomic aspects that might be involved.

From a blog post by Cort in 2015 at https://www.healthrising.org/blog/2015/01/31/increasing-energy-neuroimmune-klimas/

...We may have gotten a taste of what’s coming year or so ago when Doctor Klimas said, if I remember correctly, that the autonomic nervous system tanks first during exercise – and then drags the immune system down with it.​

I don't recall ever seeing that finding published, which is frustrating because it sounded interesting.
 
But this is a mix of things assumed to relate to haemodynamic causes of OI, not OI per se. And I think they may be muddled. If you have OI due to a fall in blood pressure when standing sitting with the feet up may be the worst thing to do because it will exaggerate the difference with standing. If the problem is gravitation of water to the leg tissues, as in right heart failure, then again sitting with feet up will only exaggerate the problem because there will be more room for the feet to accommodate fluid on standing.

Wondering if it's best to avoid sitting with your feet up then, whenever possible, and alternate between lying flat and sitting normally in order to 'train' the ANS, if that's possible. That would be hugely disabling in the short term because people like me would spend almost all day lying flat, but obviously worth it eventually if some improvement could be had.

The question is, can the ANS be trained (in PWME, who can't exercise)? There was a paper on a small RCT by Julia Newton on this in 2009 with results tending in the right direction, with an intervention that involved standing against a wall for longer and longer periods ("Home orthostatic training in vasovagal syncope modifies autonomic tone: results of a randomized, placebo-controlled pilot study"):

https://academic.oup.com/europace/article/12/2/240/431552

but it was never followed up.
 
...We may have gotten a taste of what’s coming year or so ago when Doctor Klimas said, if I remember correctly, that the autonomic nervous system tanks first during exercise – and then drags the immune system down with it.

That sounds like rubbish. Maybe Cort has misquoted, maybe not, but I can think of no means by which a 'tanking autonomic system' could 'drag down' the immune system. And I am quite sure nobody has any evidence for it!
 
That sounds like rubbish. Maybe Cort has misquoted, maybe not, but I can think of no means by which a 'tanking autonomic system' could 'drag down' the immune system. And I am quite sure nobody has any evidence for it!

Been digging a bit harder - more here from Cort in May 2018:

Klimas should know – she’s been intensively charting how ME/CFS patients’ systems go off the rails during exercise for several years now. She’s measured every cytokine, neuropeptide, etc. she can at 8 timepoints before, during and after exercise in 50 women with ME/CFS, 25 women with FM, 50 men with ME/CFS and 50 men with GWI.

She’s gathered a vast amount of data and that data is telling her that ME/CFS patients’ immune systems basically go nuts during the first 15 minutes of exercise. Four hours later, oxidative stress kicks in and the autonomic nervous and endocrine systems and metabolism get hit — but it’s the immune system that kicks everything off.​

So maybe what he's talking about is the sequence in which issues appear, rather than the ANS causing the immune system to tank.

Again, if Nancy Klimas has published on this, I haven't noticed, but then I don't notice much.

Not sure what the implications of any of this would be for ANS training, if any.
 
She’s gathered a vast amount of data and that data is telling her that ME/CFS patients’ immune systems basically go nuts during the first 15 minutes of exercise. Four hours later, oxidative stress kicks in and the autonomic nervous and endocrine systems and metabolism get hit — but it’s the immune system that kicks everything off.

This is definitely nonsense, @Sasha. Moreover, it seems to be the opposite of what he said before. I am afraid I don't take Cort's interpretation of science seriously. I am also pretty sceptical about Nancy Klimas's statements if they are like the bit she says in Unrest. If anybody has found anything substantive about the immune system in ME it should be there in the published literature to see and it isn't.
 
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