Health rising blog post, by Cort Johnson, 16 August 2017: Exercise Tests Suggest Autoimmunity Causes the Exertion Problems in Chronic Fatigue Syndrome, Fibromyalgia and POTS

Researchers and doctors get interested in ME/CFS in different ways. Many have a personal connection, but for David Systrom,  a pulmonologist, it was all about demand. He didn’t seek chronic fatigue syndrome patients out – quite the contrary.  When Systrom was given control of a clinical cardiopulmonary lab, he started doing invasive cardiopulmonary exercise tests (iCPET’s) on people with exercise intolerance. Once word of that got out, chronic fatigue syndrome, fibromyalgia, POTS and other patients starting pouring in.

It wasn’t the patients seeking Systrom out – it was their doctors; they finally had a place to send their strange exercise intolerant patients to. Rheumatologists, cardiologists, neurologists, and infectious disease specialists have gladly sent their patients his way for years.  It’s not a small number. Systrom suggests that 10 percent of people with exercise intolerance fit this profile. Those referrals have lead to 1,500 highly sophisticated exercise tests, about 700 of which were done on people with ME/CFS/FM/POTS.

Systrom’s had his eye on chronic fatigue syndrome (ME/CFS) for a while, but up until now he’s been looking at exercise intolerance in general. That’s why, despite the fact that he has one of the biggest, and certainly the most sophisticated, database of exercise results in ME/CFS, he’s mostly unknown to researchers and patients.

Armed with a grant from an anonymous donor to The Solve ME/CFS Initiative (SMCI) to support his work, Systrom, is for the first time focusing a study solely on ME/CFS.

Invasive Cardiopulmonary Exercise Testing (iCPET)
Systrom has taken exercise testing in ME/CFS to the next level with his invasive cardiopulmonary exercise testing (iCPET). Non-invasive cardiopulmonary exercise (CPET) testing can do a lot of things. It can demonstrate that exercise intolerance is present, define the aerobic and anaerobic contributions to exercise, determine if lung problems are present and others, but with an iCPET researchers can dig much deeper.

Systrom’s an acknowledged expert in the iCPET field; in 2013 he was the senior author of the first review paper on iCPET and in 2016 he co-wrote the first methodology paper explaining how to do it correctly.

One catheter goes into the pulmonary artery

Invasive CPET’s involve the insertion of catheters into the pulmonary artery and radial arteries that monitor blood flow, oxygen content and other factors. These catheters allow researchers to determine if the problems with oxygen are occurring in the lungs or in the muscles, where oxygen uptake is occurring and so on. Because iCPET can determine changes in venous blood O2 occurring with exercise, they’re able to determine how much oxygen the muscles are using. The technique can therefore be used to diagnose mitochondrial issues.

iCPET tests needed to identify three under-recognized causes of exercise intolerance, the third of which concerns ME/CFS:  preload failure or the inability of the blood vessels to provide the heart with enough blood to pump effectively.  Several studies suggest that preload failure is causing the small hearts in ME/CFS.

In the 2013 review article Systrom explained what happens (or should happen) when we exercise.

  1. Muscles need oxygen to generate energy.
  2. During exercise, increased breathing (ventilation) in the lungs and increased gas exchange between the lungs and blood provides more oxygen to the blood.
  3. First the heart increases it’s stroke volume so that it can shoot more blood out to the muscles.
  4. Once the heart maximum stroke volume is reached, the heart rate begins to increase in order to pump out more and more blood.
  5. In order to provide the increased levels of blood to the heart, the veins leading to it enlarge so that they can accommodate more blood.

It’s All About Oxygen
First, aerobic (oxygen-oriented) energy production mostly prevails. When the limits of aerobic metabolism are reached, though, one’s “anaerobic threshold” is reached. At that point, a non-oxygen way of producing energy called anaerobic metabolism becomes prominent. Two toxic byproducts of anaerobic metabolism, lactate and CO2, build up and cause fatigue, pain, etc.  (Anaerobic thresholds are identified during the CPET test by an abrupt increase in CO2 levels). Here’s the key part for ME/CFS, FM and POTS patients from Systrom’s 2013 paper:

“People with low anaerobic thresholds; that is, people who quickly exhaust their ability to generate energy aerobically and rapidly enter into anaerobic metabolism have one of two problems: either the oxygen isn’t getting to the mitochondria in their muscles or the mitochondria aren’t taking it up….

In a June interview, Systrom stated that about half of his patients have POTS/ ME/CFS or FM. When he tests them, a couple of different patterns show up – a pattern of dysautonomia, which reflects problems with the blood vessels, and reduced oxygen uptake pattern reflecting other problems.

  • Dysautonomia – the primary problem is inadequate venoconstriction; i.e. the autonomic nerves are not constricting the veins enough to propel sufficient amounts of blood (i.e. oxygen) to the heart for exercise or other activities to take place. Damage to the nerves in the arteries may be present as well.
  • Reduced skeletal muscle oxygen uptake -the  mitochondria are not taking in as much oxygen as they should.
  • Genetic issues – are not nearly as common as the other two, but Systrom can at times find genetic issues.

Read more about Systrom’s research and potential drug treatment (mestinon)


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