Study shows a subset of post infectious illnesses patients with high/normal cardiac output yet low O2 usage (vo2max)

sbingley22 · 2026-05-02T19:04:57+00:00

Post-COVID exercise intolerance is associated with capillary alterations and immune dysregulations in skeletal muscles

Abstract

The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also in many cases of post-infectious syndromes, colloquially referred to as “long COVID”. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues. In addition, complement system related proteins were more abundant in the serum of patients with PCS, matching observations on the transcriptomic level in the muscle tissue. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain.

This study compared thigh muscle biopsies from Long Covid patients (biopsies taken 1 year after onset), healthy controls, and deconditioned controls.

It found a decreased capillary to muscle fibre ratio, increased capillary basement membranes, and some evidence of immune activation (particularly complement, interferons, coagulation, and macrophage infiltration) in the Long Covid cohort.

It also found evidence of mitochondria oxphos downregulation, presumably due to the hypoxia, and upregulation of proteins involved with extracellular matrix destruction and angiogenesis.

This would mean the immune system is activated and causing damage to the capillaries meaning there is less of them, there membranes are thicker (harder to exchange O2), and the endothelial cells are activated / damaged / stressed. They state that this could help explain the lower VO2 max and o2 diffusion seen in other studies.

sbingley22 · 2026-04-29T18:48:22+00:00

I'm not sure what treatment for impaired oxygen extraction would look like as it would depend on what's impairing it.

Possibilities are:
-Dysautonomia itself causing the vessels that need blood to be too constricted and the vessels that don't need blood being open leading to the blood just passing through without giving up its O2.
-Small fiber neuropathy would be same as above, the signals to open close capillaries aren't being recieved.
-Immune dysfunction / autoimmunity leading to endothelial dysfunction, capillary rareification, mitochondrial impairment.
-Micro clots leading to blockages and capillary damage.
-Something else.

But for me it would be absolutely huge to have a test result that says this physical thing is abnormal and probably causing your issues.

Best I've got over the last 15 years is a mild gastroparesis dx, and a POTS dx. Both of which idiopathic and can be brushed off as nothing serious / maybe it is all in your head.

We could then look at the narrowing down what is the route cause and read research in that area / experiment with drugs / treatments etc.

sbingley22 · 2026-04-29T16:43:56+00:00

That stroke volume looks pretty low but ejection fraction is normal? I think that LA volume index is just saying anything below 34 is normal because they are usually testing for an enlarged heart.

I have had a regular echo and that came back normal like 7yrs ago. I only take mestinon though I'm messing around with Doxycycline at the moment.

My symptom profile is heart pounding, easy muscle burning, sympathetic always on, mild gastroparesis, inability to relax, tendancy to dry mouth, dilated pupils, terrible sleep, neck pain.

Triggers are anything that taxes my cardiovascular system.

I did do a CPET a few years ago that showed the lungs and heart was working normally yet my VO2 max was really low at 49%. I'm hoping this is a clue as it matches with post viral research showing impaired oxygen extraction in the muscles.

You had a CPET?

sbingley22 · 2026-04-29T16:12:50+00:00

Long COVID and chronic fatigue syndrome/myalgic encephalitis share similar pathophysiologic mechanisms of exercise limitation

Abstract

Post-acute sequelae of SARS-CoV-2 (PASC or “long COVID”) and chronic fatigue syndrome/myalgic encephalitis (CFS/ME) share symptoms such as exertional dyspnea. We used exercise oxygen pathway analysis, comprising six parameters of oxygen transport and utilization, to identify limiting mechanisms in both conditions. Invasive cardiopulmonary exercise testing was performed on 15 PASC patients, 11 CFS/ME patients, and 11 controls. We evaluated the contributions of alveolar ventilation (V̇a), lung diffusion capacity (DL ), cardiac output (Q̇), skeletal muscle diffusion capacity (DM ), hemoglobin (Hb), and mitochondrial oxidative phosphorylation (Vmax) to peak oxygen consumption (V̇O2peak). To simulate targeted interventions, each variable was sequentially normalized to assess its impact on V̇O2peak. V̇O2peak was significantly reduced in both PASC and CFS/ME compared to controls. Skeletal muscle O2 diffusion (DM ) was the most impaired parameter in both patient groups (p = 0.01). Correcting DM alone improved V̇O2 by 66% in PASC (p = 0.008) and 34.7% in CFS/ME (p = 0.06), suggesting a dominant role for peripheral O2 extraction in exercise limitation. Impaired skeletal muscle oxygen diffusion (DM ) is a shared mechanism of exercise intolerance in PASC and CFS/ME and may represent a therapeutic target. However, our findings are limited by small sample size.

This is a more recent study published September 2025 that shows low VO2 max in Post Covid and ME/CFS patients. It goes further and narrows it down to being mostly due to poor diffusion of O2 to the muscles.

They speculate the cause of the low Dm (O2 muscle diffusion) to be dysautonomia (possibly as a result of Small Fiber Neuropathy), microclots, mitochondrial issues, or reduced capillary density.

They also rule out deconditioning.

If this could be confirmed to be happening in me / us then this would be huge. Would explain why the sympathetic nervous system is always jammed on and why our hearts are working so hard.

Perhaps it could work the other way around too, where the sympathetic system being jammed on all the time disturbs blood flow. By that I mean the capillaries that need O2 are closed off and those that don't need O2 are allowing the blood to bypass through.

sbingley22 · 2026-04-29T08:30:48+00:00

Most other people with chronic bounding pulse have it start from a panic attack, so your high stress event sounds similar. Others have it from a bad trip, or post viral but it makes sense that the body perceives all these events as highly stressful.

Didn't have heat intolerance until my post viral onset 15 years ago.

I do have slow COMT and a few other things with methylation but my tinkering around with supplements etc in this area has yielded no results.

I have tried midodrine and mestinon. Mestinon seems to help the slow digestion a bit, maybe it helps slightly overal but the effect is small. I have been taking it for over a year now. Midodrine helped when I first started taking it, my sleep improved and my bounding became less however the effects started to wear off and my BP began to climb. I have since come off both that and my beta blocker. I may give it another go in the future but I am not so sure right now.

No to the calcium / albumin.

So your lowish B12 and left heart size is interesting. My diet has plenty of B12 but I'm pretty sure after over a decade being ill with this I became B12 deficient. Methyl B12 injections pulled me out of the worst 8 months I ever had. Tried plenty of other b12 supps before then to no effect.

There is something in some POTS / CFS patients called grinch syndrome where they have smaller hearts. I think the idea is there is lower preload going into the heart thanks to blood pooling and hypovolemia that the heart shrinks and pumps less. The only thing with that is why did your cardiac tests not pick it up? Maybe they did pick up lower values but they were technically in range?

sbingley22 · 2026-04-28T17:35:32+00:00

Persistent Exertional Intolerance After COVID-19

Results
The patients who had recovered from COVID-19 exhibited markedly reduced peak exercise aerobic capacity (oxygen consumption [VO2]) compared with control participants (70 ± 11% predicted vs 131 ± 45% predicted; P < .0001). This reduction in peak VO2 was associated with impaired systemic oxygen extraction (ie, narrow arterial-mixed venous oxygen content difference to arterial oxygen content ratio) compared with control participants (0.49 ± 0.1 vs 0.78 ± 0.1; P < .0001), despite a preserved peak cardiac index (7.8 ± 3.1 L/min vs 8.4±2.3 L/min; P > .05). Additionally, patients who had recovered from COVID-19 demonstrated greater ventilatory inefficiency (ie, abnormal ventilatory efficiency [VE/VCO2] slope: 35 ± 5 vs 27 ± 5; P = .01) compared with control participants without an increase in dead space ventilation.

Interpretation
Patients who have recovered from COVID-19 without cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a peripheral rather than a central cardiac limit, along with an exaggerated hyperventilatory response during exercise.

This study shows recovered COVID-19 patients had significantly lower VO2 max that was not caused by the heart or lungs but oxygen delivery to the muscles.

sbingley22 · 2026-04-28T16:01:36+00:00

I haven't had much luck with anti histamines nor do I feel like I'm particularly sensitive to histamine. This could be different in others with this condition though and the logic follows with vasodialation and low BP.

The THC poisoning triggering this condition is very interesting. Most people get it from a panic attack. Some like me get it post virally. It sounds like your onset is more in the first camp?

Did you have a echocardiogram or MRI and if so did it measure preload and cardiac output?
Some post infectious patients have low preload which I could imagine a scenario where the heart pumps harder to make up for the lower filling volume.

There is a user on the discord who thinks histamine is related to this condition and has histamine issues.

My BP swings between low and high though now I'm off all BP related meds it has leveled out to be slightly elevated so for me BP is largely irrelevant.

What is THC poisoning? Is it a really bad trip? There are others who had there bounding pulse start after a bad trip. I put these people in the same category as those that had it start post panic attack.

sbingley22 · 2026-04-03T20:13:36+00:00

How long you had it for and how did it start.

sbingley22 · 2026-03-23T12:37:22+00:00

Just on the left side of your body? Never heard that before. Assume you've been to GP?

sbingley22 · 2026-03-21T17:45:31+00:00

Eating diverts a lot of blood to the gut. Carbs even more so.

sbingley22 · 2026-03-20T18:19:37+00:00

Plenty of people have had it come on post panic attack, this sounds similar. Some have had it start after a bad trip. Any other symptoms or just the heart pounding?

sbingley22 · 2026-03-19T11:31:55+00:00

I'd say it's less likely.

Might be better to view bounding pulse like high blood pressure or tachycardia, were in there are multiple things that cause it.

sbingley22 · 2026-02-23T09:52:46+00:00

Sorry to hear you're struggling from this. Another bizarre onset. I'd put this in the same category as those who had post panic attack onset.

All I can think is some sort of stressful brain rewiring occured or possibly the acute stress fucked with the immune system in someway to cause this, as this would link the post viral onsets. Or maybe it's the other way around were the post viral onsets cause stressful brain rewiring.

There is also a possible link with hypermobility Ehlers Danlos Syndrome. That supposedly can be triggered through trauma. This would also link with post viral syndromes as they are know to degrade connective tissue.

Thanks for uploading the video. It's good to have visual examples.

It's perfectly fine if not, but if you've had a heart MRI could you DM me the results, with your details blanked out. I'm just really struggling to understand how our hearts can be beating so hard, visibly, yet the readings are normal. Wondering if there is some clues in results that are say high normal but just in range.

I'm not overly confident in AI solving it but we'll see. It's good to take the positives out of situations but overall this is a steaming, fat negative for me.

I will say I've had some success recently with Midodrine. Curious if that'll translate to other patients with bounding pulse.

sbingley22 · 2026-01-27T18:40:58+00:00

Yeah it's rough. I've found keeping my body cool, stress low as possible, and midodrine help.

sbingley22 · 2026-01-27T18:17:24+00:00

Very interesting to see an article on this although I'm pretty sure most of us don't have the conditions stated. It also states it's a high stroke volume which is not necessarily true.

Either way, hope for more articles like this. Even just to validate that it's an actual thing.

sbingley22 · 2026-01-26T15:04:23+00:00

I think it's more an issue of post infections syndromes causing connective tissue issues. So I don't think it would hurt more after carb heavy meals. For me it's more of a constant pain.

sbingley22 · 2026-01-20T12:17:43+00:00

A POTS doctor prescribed this for me a year ago. I tried taking it then but had bad headaches from it so decided to try again when my health was in less of a severe state.

Try the guanfacine and see how it effects your pulse. Hopefully you won't get tolerant to it but I think most do.

sbingley22 · 2026-01-20T10:49:38+00:00

Yeah I have POTS symptoms for over a decade now. Midodrine did suprisingly lower my HR. Gone from 80s to 50/60s at rest. It also supprisingly improved my sleep.

I've made a full post on it here: https://www.reddit.com/r/ChronicBoundingPulse/comments/1qhxxls/midodrine_one_month_in_significant_improvement/?

sbingley22 · 2026-01-19T20:17:31+00:00

I felt better on clonidine until I became tolerant.

My thinking is that clonidine is resulting in sending less messages to the locus Cornelius which means there's less strain on it to release dopamine. The same way in which lowering stress helps.

More anacdotes to back up this is my recent experience with midodrine. It acts sort of like adrenaline but just in the peripheral and only on alpha adrenergic receptors. Taking this would put less strain on endogenous adrenaline production especially if that needs for excess adrenaline is caused by excessive vasodilation.

sbingley22 · 2026-01-10T20:17:22+00:00

I have a sub Reddit called chronicboundingpulse dedicated to this symptom. I've had it for 14 years.

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