Event: Grand Rounds: Pathophysiology of Exercise Intolerance in Chronic Fatigue Syndrome Event Date: May 5th, 2020 David Systrom, MD

John Mac

John Mac

Senior Member (Voting Rights)
Join us virtually at this month’s Integrative Medicine Grand Rounds to hear Brigham pulmonologist Dr. David Systrom speak about the pathophysiology of exercise intolerance in chronic fatigue syndrome, including a clinical case with a patient perspective.

Resources:
Presenter: David Systrom, MD
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https://oshercenter.org/oc-event/gr...cise-intolerance-in-chronic-fatigue-syndrome/
 
For me, the most interesting part was toward the end (starting at 36.05).




"Just in passing, I'll show you all three slopes - low - sort of normal - and then high slopes of blood flow, pulmonary blood flow to VO2. All have slightly depressed VO2 peaks. The patients with the lower blood flow have the lowest cardiac output over here and then there's this high blood flow group out to the right. They are the patients with the most impaired systemic oxygen extraction.

"All three groups have preload failures, as we previously described in the Olden[?] publication I showed you. But what's of interest is this high flow group appears to have what might be left to right shunting in the periphery of outer muscle.

"So blood flow is not appropriately getting to the mitochondria and being taken up. So that's reflected by impaired oxygen extraction. Blood flow is going around and around in the pulmonary circuit, but not effectively getting to the mitochondria and being taken up.

"There is one alternative diagnosis that I'll give you here in a second.

"So what we've newly discovered is there is additional vascular dysregulation in a subset of patients with MECFS that reflects arteriolar dysfunction. Almost everybody with MECFS appears to have some impairment of venoconstriction and priming the pump [of] the right heart. But additionally, there is a subset of patients who appear to have impaired oxygen extraction and high pulmonary flow that might reflect left-to-right shunting.

"An alternative explanation for all of this is intrinsic mitochondrial dysfunction and this is an area that we are researching currently.

"We have a preliminary data to suggest that, yes, there is a subset of patients with MECFS, and if one does a frozen muscle biopsy appropriately interrogated [unintelligible] for electron transport chain abnormalities, it's abnormal.

"So I think there are subsets of MECFS in terms of their exercise intolerance; there's a lot of vascular dysregulation; preload failure seems to be ubiquitous and a subset of patients additionally appear to have evidence of either left-to-right shunting, mitochondrial dysfunction out in the periphery in the muscle - or both."

[bolding mine].
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If I understood this correctly, there's a particular group of patients (the high blood flow group) that has the highest impairment of oxygen extraction. In other words, when their blood returns to their hearts, it has too much oxygen in it - showing that insufficient oxygen was extracted by the cells.

One explanation would be that oxygenated blood is bypassing the cells at a very local level, being "shunted" around the cells from the arterial system to the venous system. This may be happening at the level of the second smallest vessels - the arterioles and venules. He uses the term "arteriolar dysfunction."

An alternative explanation might be that the mitochondria in the cells are dysfunctional and aren't using enough oxygen. He says they have preliminary evidence to suggest that.

So the poor oxygen extraction could be caused by arteriovenous shunting, mitochondrial dysfunction - or both.

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If this has something to do with the next to smallest of blood vessels, the arterioles and venules, it wouldn't be the first time that they have been implicated in ME/CFS.

One of the historic outbreaks of ME occurred in 1975 at the Mercy San Juan Hospital Medical Center, located in a suburb of Sacramento, California. It was attributed to "infectious venulitis" - an inflammation of the venules.

http://www.oocities.org/sezar99q/MECFSInfectiousVenulitis.html
 
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Forbin said:
For me, the most interesting part was toward the end (starting at 36.05).






If I understood this correctly, there's a particular group of patients (the high blood flow group) that has the highest impairment of oxygen extraction. In other words, when their blood returns to their hearts, it has too much oxygen in it - showing that insufficient oxygen was extracted by the cells.

One explanation would be that oxygenated blood is bypassing the cells at a very local level, being "shunted" around the cells from the arterial system to the venous system. This may be happening at the level of the second smallest vessels - the arterioles and venules. He uses the term "arteriolar dysfunction."

An alternative explanation might be that the mitochondria in the cells are dysfunctional and aren't using enough oxygen. He says they have preliminary evidence to suggest that.

So the poor oxygen extraction could be caused by arteriovenous shunting, mitochondrial dysfunction - or both.

----------------------​

If this has something to do with the next to smallest of blood vessels, the arterioles and venules, it wouldn't be the first time that they have been implicated in ME/CFS.

One of the historic outbreaks of ME occurred in 1975 at the Mercy San Juan Hospital Medical Center, located in a suburb of Sacramento, California. It was attributed to "infectious venulitis" - an inflammation of the venules.

http://www.oocities.org/sezar99q/MECFSInfectiousVenulitis.html
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The description of the 1975 outbreak is very interesting, he describes very well many symptoms that most of us have.
 
Thank you for transcribing the video @Forbin.

At 40:45, Systrom shows that his patients are on average taking 234mg +/- 83mg of Mestinon. That's about 4x60mg pills per day. Wondered if he bumped it up at some point? From a blog post or two from some of Systrom's patients, I recall he was using 3x60mg.

ETA: It's pleasant to see a presentation with tons of hard data/evidence.
 
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Thanks for posting this video. Does this suggest that people may be born with these sorts of vascular/cardiac issues?

What I found most interesting about Mona's testimony was that she never used the words PEM, or malaise. Also, when our family member was on the mestinon, aside from the side effects, the medication did stimulate the system. However, after 6 months, such a spectacular crash ( from exercise, I guess)took place that it was frightful to look at, and it would last for a year or more, and then there was always a more permanent down turn.

The use of Ritalin also worries me. Dr Teitelbaum used to suggest this too (as well as mestinon). The treatment proposals are not really new from the list that was in the video. These stimulants push the body, but a horrific crash can ensue many months down the line. As for anti depressants, well, most ME patients have been proposed these, and many have taken and tried them, and many have said they made them feel worse. I did find the work that was done by Dr Systom to be very interesting; it seems thorough, though other doctors many decades ago have suggested these problems. And I wonder if there is anything other than Mestinon that could help with these vascular/cardiac issues.

I just want to add that all the research really just adds to so much confusion: this is wrong that is wrong, the immune system, the endocrine system, collagen, cardiac system, GI function, and something in the blood, and viruses, metabolic trap, Dr. Naviaux's theory, etc , etc., and everyone finds some problem in the body, and there are all these pieces of a puzzle lying on a table and no one can seem to put the puzzle together. Very discouraging all this.
 
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cassava7 said:
Thank you for transcribing the video @Forbin.

At 40:45, Systrom shows that his patients are on average taking 234mg +/- 83mg of Mestinon. That's about 4x60mg pills per day. Wondered if he bumped it up at some point? From a blog post or two from some of Systrom's patients, I recall he was using 3x60mg.

ETA: It's pleasant to see a presentation with tons of hard data/evidence.
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Near the end he says he usually starts patients on 3 x 30mg/day then after a couple of weeks moves it up to 1 x 180mg slow release once a day.

I was interested that he says he combines mestonin treatment with graded exercise therapy, and his test of effectiveness is to do a single CPET after some time on the treatment and finds they have got fitter. The patient who spoke talked about being able to do more, including some jogging. I think she said at the start of taking mestonin she was already able to walk 3 miles without stopping (and without PEM), and her CPET showed above average fitness, so to me that says her ME was very mild by then anyway. It wasn't clear, I don't think, how long she had been on Mestonin.
 
Trish said:
Near the end he says he usually starts patients on 3 x 30mg/day then after a couple of weeks moves it up to 1 x 180mg slow release once a day.

I was interested that he says he combines mestonin treatment with graded exercise therapy, and his test of effectiveness is to do a single CPET after some time on the treatment and finds they have got fitter. The patient who spoke talked about being able to do more, including some jogging. I think she said at the start of taking mestonin she was already able to walk 3 miles without stopping (and without PEM), and her CPET showed above average fitness, so to me that says her ME was very mild by then anyway. It wasn't clear, I don't think, how long she had been on Mestonin.
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Yes, Trish, imagine walking 3 miles!! I am well, and I cannot at this point walk 3 miles!!! So many sick folks can't even walk around their houses adequately, some stay in bedrooms in the upstairs parts of their houses--never able to come downstairs for years at a time. I wish we could hear a bit more about the whole spectrum of patients who were being treated by Dr Systrom--would be very interesting.
 
A complete (preload) failure
Paolo Maccallini

Introduction

Some days ago, David Systrom offered an overview of his work on cardiopulmonary testing in ME/CFS during a virtual meeting hosted by the Massachusetts ME/CFS & FM Association and the Open Medicine Foundation. In this blog post, I present an introduction to the experimental setting used for Systrom’s work (paragraph 1), a brief presentation of his previous findings (paragraph 2), and an explanation of his more recent discoveries in his cohort of patients (paragraph 3). In paragraph 4 you’ll find a note on how to support this research.
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https://paolomaccallini.com/2020/11/24/a-complete-preload-failure/
 
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