Role of Capillary Size in ME

Wishful

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While looking up something else, I came across an interesting research paper from 2008: The role of impaired capillary blood flow in ME. http://www.investinme.org/ArticleJ21-Role-of-Impaired-Capillary-Bloodflow.shtml

It seems to imply that impaired blood flow in capillaries is the main cause of ME symptoms. Has this been proven false by newer research? It's an attractive theory, and it connects up nicely with some known aspects of ME. However it seems that if it were true that ME is the result of reduced blood flow in various parts of the body, it should be treatable by something like Pentoxifylline. I've searched here, and found some people had tried Pentoxifylline, but no reports of huge reductions in ME symptoms. Aspirin has been proven to not reduce blood viscosity or increase RBC deformability, so that's not a viable test of the hypothesis. NSAIDs in general are supposed to prevent constriction of blood vessels, but I haven't noticed aspirin, acetaminophen or ibuprophen having any effect on my ME symptoms. Has anyone noticed any significant reduction in ME symptoms from taking blood flow improvers?
 

Mary

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@Wishful, the first sentence reads:
As long ago as the 1980s, Dr Les Simpson in New Zealand found that the red blood cells of patients with CFIDS were deformed and when deformed, they cannot get through the capillary bed, causing pain.
I don't have pain associated with ME/CFS, and I don't know if my red blood cells are deformed, but I do fit Ramsay's definition of ME as set forth in the article, including
a unique form of muscle fatigability whereby, after even a minor degree of physical effort, three, four or five days, or longer elapse before full muscle power is restored;
I haven't read the whole thing, but based on my own symptoms (or lack thereof) it would seem that impaired blood flow in the capillaries is not the main cause of ME symptoms, if impaired blood flow to the capillaries always causes pain. Because I don't have pain, but I do have ME. But I guess it's possible that one could have impaired blood flow without pain - I can only guess here.
 

Hip

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Dr Leslie Simpson's ideas on red blood cell shape and deformability in ME/CFS are old, but Ron Davis has recently looked into it.

The idea that ME/CFS is caused by red blood cells being too large or not sufficiently deformable to pass through capillaries is interesting, but for me what tends to argue against this theory is the fact that hyperbaric oxygen therapy (HBOT) usually does not do anything major for ME/CFS patients.

Since HBOT dissolves a lot of oxygen in the liquid water component of the blood, you should get oxygen delivery in the capillaries even if red blood cells are too large to travel down them. Thus you might expect HBOT to dramatically improve ME/CFS if this red blood cell theory were correct, but it does not.
 

S-VV

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I do believe that microcirculatory abnormalities play a role in ME/CFS, maybe even a big role. There are papers that postulate that the principal effector cause of the damage of sepsis is impaired microcirculation. Here is a simple experiment I do: Raise you arm up and notice how long it takes to get the feeling of "not enough blood". Its a strange feeling, but I'm sure most of you have felt it at some point or another. I get the feeling almost immediately.

Hypoperfusion of tissue due to capillary dysfunction would explain the fact that there is impaired oxygen utilisation, that is, the oxygen is inhaled, but it is exhaled out, without being used.

Pentoxyfiline is not very effective, even for what is was meant for, intermittent claudication. I suspect a better treatment would be a vasodilator, I have personally tried nitroglycerin (NO donor), and I find it helpful for physical exertion, although it gives me a headache.

Because of that, I have been supplementing Arguinine, Citruline and Methylfolate to raise NO.
 

S-VV

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@S-VV What do you mean by not enough blood feeling in arm when raised? For me I get almost instant lactic acid build up (burning feeling) that increases the longer I hold.
Its the same feeling as when you lay down and put the legs on a chair, and you feel the blood flowing down. I also experience the lactic acid, burning feeling, but this is different, it feels as if there is blood flow from the arm to the body
 

Hip

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Raise you arm up and notice how long it takes to get the feeling of "not enough blood". Its a strange feeling, but I'm sure most of you have felt it at some point or another. I get the feeling almost immediately.
That's more likely to be due to POTS, if you have POTS.
 

Wishful

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Okay, the image of thousands of PR members sitting at their computers with one arm in the air gave me my morning smile. :) I held mine up for about a minute. A slight sensation of numbness in my fingers, and a slow buildup of normal fatigue, building towards painful fatigue I'm sure. I don't think the feelings are any more severe than if I'd done it pre-ME.

According to the paper I mentioned, capillary size would vary in different parts of the body for different people, so I might have normal or even oversized capillaries in my main muscles, and thus not show the common physical limitations of ME, but I might have undersized cerebral capillaries, resulting in the cerebral symptoms. Some people might have undersized capillaries in their gut, causing issues there; others won't.

The theory is attractive because it's easy to fit observations into it. The lack of validation by blood-flow modifiers in the 11 years since it was published seems pretty strong evidence against it. I just didn't find any discussion of the paper, and thought it was worthwhile to discuss.

I can think of one possible bet of counterevidence: the finding of areas of the brain with elevated temperature. If the problem was reduced blood flow, shouldn't there be cooler areas rather than warmer ones?
 

Hip

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If anything, I have hyperadrenergic POTS. My blood pressure shoots up to 150/95 when walking. My reclining blood pressure is 120/80
Don't you also get blood pooling in the lower extremities, and loss of blood at the upper extremities, even in hyperadrenergic POTS? So if you raise your arm, blood will drain out.

In any case, hyperadrenergic POTS involves vasoconstriction, which may also give the sense of reduced blood supply.
 

Wishful

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Well, it's possible to come up with theories to explain why HBOT doesn't support the main theory, such as something else in the bloodstream that is being held back by the RBCs slowing squeezing their way through. It's probably just as easy to find that sort of counterarguments. As another example, wouldn't frequent blockage of capillaries result in tissue damage (necrosis) in various parts of a body?

It seemed like a very clear and plausible paper on first reading. As I said: attractive. That doesn't mean that I support it. I was kind of hoping that someone else had followed that theory and found a credible refutation.
 

Hip

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After looking into this theory a few years back, my feeling is that if insufficient erythrocyte deformability does exist in some ME/CFS patients, it may be a further burden for those patients; but my guess it that it is not the basic cause of ME/CFS.

All these theories are worth considering and experimenting with though. Certain supplements can increase red blood cell deformability, like vitamin E, evening primrose oil and fish oil, so trying these may be worthwhile.

The drug isoxsuprine also makes red blood cells more flexible and deformable. One ME/CFS patient who tried isoxsuprine reported that:
I also had been diagnosed with Chronic Fatigue Syndrome. After taking the Isoxsuprine, I had much more energy and much less dizziness.
 
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JES

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It seems to imply that impaired blood flow in capillaries is the main cause of ME symptoms. Has this been proven false by newer research? It's an attractive theory, and it connects up nicely with some known aspects of ME. However it seems that if it were true that ME is the result of reduced blood flow in various parts of the body, it should be treatable by something like Pentoxifylline. I've searched here, and found some people had tried Pentoxifylline, but no reports of huge reductions in ME symptoms. Aspirin has been proven to not reduce blood viscosity or increase RBC deformability, so that's not a viable test of the hypothesis. NSAIDs in general are supposed to prevent constriction of blood vessels, but I haven't noticed aspirin, acetaminophen or ibuprophen having any effect on my ME symptoms. Has anyone noticed any significant reduction in ME symptoms from taking blood flow improvers?
Yeah and the answer to your last question is no. I trialed pentoxifylline around five years ago, it happens to be available OTC in pharmacies in my country for some strange reason. At first I reckon it slightly reduced my brain fog, which is a similar effect I get with blood thinning supplements like high-dose fish oil, ginkgo biloba, digestive enzymes and especially, bromelain. While trialing bromelain a few years ago, I thought I had found a cure, as my circulation temporarily improved hugely, which in the process reduced most of my brain symptoms. As always, this was a temporary improvement and long-term treatment with bromelain actually made me worse. The same happened with pentoxifylline, although I can't recall the details as clearly, but basically my flu-like symptoms increased over time with no benefits left. The only other side effect I noticed was increased nosebleeds.
 

Wishful

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I noticed that evening primrose oil was mentioned as a supplement for improving RBC deformability. Unfortunately, it has a very annoying side-effect. Even without taking any, I now have this stuck in my head:

"Primrose lane. Just a family on, Primrose lane..." :rolleyes:
 

pattismith

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I do believe that microcirculatory abnormalities play a role in ME/CFS, maybe even a big role. There are papers that postulate that the principal effector cause of the damage of sepsis is impaired microcirculation. Here is a simple experiment I do: Raise you arm up and notice how long it takes to get the feeling of "not enough blood". Its a strange feeling, but I'm sure most of you have felt it at some point or another. I get the feeling almost immediately.
When I raise my arm up, I feel tingling in my fingers. is it the same you are experiencing?
By the way I don't have POTS, so I don't think it is related.
 

bread.

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I could also see how EDS is such a condition where your capillaries are worse off from the beginning, I also tend to believe that this is an important issue (if it is) in me/cfs. One of the old names for me/cfs was „pale face disease“.
 
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https://www.ahajournals.org/doi/10.1161/JAHA.119.013602
Postural Orthostatic Tachycardia Syndrome Is Associated With Elevated G‐Protein Coupled Receptor Autoantibodies
Background

The etiology of postural orthostatic tachycardia syndrome (POTS) is yet to be established. The disorder is often misdiagnosed as chronic anxiety or a panic disorder because the autonomic failure in these patients is not severe. A growing body of evidence suggests that POTS may be an autoimmune disorder. Antinuclear antibodies and elevations of ganglionic, adrenergic, and muscarinic acetylcholine receptor antibodies have all been reported.
Methods and Results
We collected detailed clinical symptoms of 55 patients diagnosed with POTS. We also evaluated serum levels of autoantibodies against 4 subtypes of G‐protein coupled adrenergic receptors and 5 subtypes of G‐protein coupled muscarinic acetylcholine receptors by ELISA. Our patients had a multitude of comorbidities, were predominantly young females, and reported viral‐like symptoms preceding episodes of syncope. We detected a significant number of patients with elevated levels of autoantibodies against the adrenergic alpha 1 receptor (89%) and against the muscarinic acetylcholine M4 receptor (53%). Surprisingly, elevations of muscarinic receptor autoantibodies appeared to be dependent upon elevation of autoantibodies against the A1 adrenergic receptor! Four patients had elevations of G‐protein coupled autoantibodies against all 9 receptor subtypes measured in our study. Five POTS patients had no elevation of any autoantibody; similarly, controls were also negative for autoantibody elevations. There was a weak correlation of clinical symptom severity with G‐protein coupled autoantibodies.
Conclusions
Our observations provide further evidence that, in most cases, POTS patients have at least 1 elevated G‐protein coupled adrenergic autoantibody and, in some instances, both adrenergic and muscarinic autoantibodies, supporting the hypothesis that POTS may be an autoimmune disorder.