Orthostatic Intolerance after COVID-19 Infection: Is Disturbed Microcirculation of the Vasa Vasorum of Capacitance Vessels... 2022, Wirth and Lohn

Orthostatic Intolerance after COVID-19 Infection: Is Disturbed Microcirculation of the Vasa Vasorum of Capacitance Vessels the Primary Defect?
Wirth and Lohn

Abstract
:
Following COVID-19 infection, a substantial proportion of patients suffer from persistent symptoms known as Long COVID. Among the main symptoms are fatigue, cognitive dysfunction, muscle weakness and orthostatic intolerance (OI).

These symptoms also occur in myalgic encephalomyelitis/chronic fatigue (ME/CFS). OI is highly prevalent in ME/CFS and develops early during or after acute COVID-19 infection.

The causes for OI are unknown and autonomic dysfunction is hypothetically assumed to be the primary cause, presumably as a consequence of neuroinflammation. Here, we propose an alternative, primary vascular mechanism as the underlying cause of OI in Long COVID.

We assume that the capacitance vessel system, which plays a key role in physiologic orthostatic regulation, becomes dysfunctional due to a disturbance of the microvessels and the vasa vasorum, which supply large parts of the wall of those large vessels.

We assume that the known microcirculatory disturbance found after COVID-19 infection, resulting from endothelial dysfunction, microthrombus formation and rheological disturbances of blood cells (altered deformability), also affects the vasa vasorum to impair the function of the capacitance vessels. In an attempt to compensate for the vascular deficit, sympathetic activity overshoots to further worsen OI, resulting in a vicious circle that maintains OI. The resulting orthostatic stress, in turn, plays a key role in autonomic dysfunction and the pathophysiology of ME/CFS.

https://www.mdpi.com/1648-9144/58/12/1807

 

This is a hypothesis paper, meaning it's a new perspective on existing research. The idea that OI is caused by a specific sort of vascular dysfunction is pretty novel and interesting. What types of experiment could help confirm or disprove it?

 

This is actually one of the first papers I've read in a while that seems to make sense. Going to start shooting this over to other sources to get thoughts.

 

Is it? I thought this was a pretty old hypothesis. Just that, a hypothesis, but I'm pretty sure I've seen it described this way before. It makes a lot of sense, the sum of all capillaries is actually huge, even a small reduction in their ability to do their job will have a huge impact since it's hugely multiplied. They cover a lot of space.

I'm not sure how much it explains reduced blood flow to the brain, though. Maybe that's just a compensatory mechanism. Unless it also affects the main arteries. There's probably a few dynamic feedback looks involved to explain the whole thing.

 

Darn it, I wish there was at least ONE aspect of ME pathology that had rock solid research, meaning replicated multiple times. I'm tired of the lack of research into a condition that's so profoundly disabling.

 

Before reading this paper, I had no idea that blood vessels had blood vessels. The human body is amazing.

 

I think we need to keep in mind that about 30-50% of us have an underlying autoimmune disorder per most of the POTS specialists including Dr Klimas. That is why they do antibody panels, skin punch biopsies, sweat tests, etc. To see if there is any kind of ongoing neurological damage.

The rest of us may have this issue, if immune testing comes back normal...? So I don't think we will have a 'one aspect' of ME pathology, although Dr Systrom does report preload failure across the board for his ME/CFS and POTS patients, per his talk and slideshow yesterday.

 

Hutan, do you see anything where treatment/medications could be applied to this issue? I wish I was more intelligent about this stuff...

 

Sorry, but reading the abstract I have to conclude that this is written by people with no clue what they talking about.

We don't even have any meaningful evidence of microvascular dysfunction in Long Covid or ME yet.

 

Do you think the pursuit of looking into how preload failure starts is a worthy cause, given Dr Sytrom's findings in POTS and/or CFS patients across the board?

I've really struggled with finding the right medications for my POTS/CFS, and I am beginning to wonder if being on Carvedilol for the increased heart rate is maybe the wrong way to go about it... Maybe pursue increasing the vascular 'squeezing effect' vs tamp down the autonomic response?

 

I've read through the paper and some of the proposed concepts make sense to me both from a theoretical and patient experience perspective.

Building from Hutan's post above on what capacitance vessels and the vasa vasorum are [1], the paper notes the following potential impairments —

They note that the large systemic veins, which form the bulk of the blood volume capacitance system, carry de-oxygenated blood and so the blood vessel wall itself is dependent of the vasa vasorum to provide oxygen-rich, "arterial" blood to allow the vessel to function in this environment: i.e. expand and contract to maintain circulatory homeostasis, esp in response to orthostatic challenge.

They start from the position that the "microclot" theory is established — and it is not.

From there they propose that impaired supply to the vasa vasorum will lead to undercompensation of the (vein's) intraluminal oxygen content. This would then result in poor performance of the vessel's smooth muscle and consequent autonomic compensations —

I would like to propose an alternative explanation that is similar but does not rely on microcirculation impairment.

It's been noted that when tested in LC patients, peripheral venous oxygen saturation is very low. (Mine has been 15%, 22% and 46% - all well below the expected 60-70%). Perhaps this much lower resulting partial pressure of oxygen it too low for the vasa vasorum to compensate for - even if they are functioning normally. It could be that a metabolic / mitochondrial process leads to this peripheral low SvO2 (and I note that central values are normal to high in Systrom's iCPET research). Also, failure of NO bioavailability may be compounding the capacitance vessel failure.

As limited as my subjective evaluation of my experience is, I suspect the tachycardia / OI symptoms are due to failure at the vascular level, rather than CNS / peripheral neural.

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[1] Vasa Vasorum in Normal and Diseased Arteries (2014)

 

I always felt weird how everyone clings to the term "dysautonomia", while it is not well established if the tachycardia is caused by a defective autonomic nervous system, or if it is working correctly, but jsut compensating for defective vasculature.

In my case, I am convinced that my OI is vascular in nature. None of the parasympathetic "boosters" ever had an effect on me. I have tried SGB injections, tVNS, etc.

But with all this money and time Long Covid is getting, why is that nobody is being able to validate this? It has been 3 years since the start of the pandemic and we still have close to 0% actual knowledge on why post-Covid OI happens. And I sense that more than half of recent LC papers just feel like recycled garbage.

 

I've been searching around the webs and can't seem to find an article I read a while back where doctors took veins of sick patients and the veins did not react like they were supposed to. It validated that the autonomic system is fine, it's just compensating for a physical abnormality elsewhere in the body.