Jo's comments in this thread are critically important, as we don't understand this properly at all, though like Tantalus, it feels is if the understanding is just beyond our grasp. We're generally looking at this assuming the problem is low blood volume and potential compromise of blood flow to the brain on standing. But as Jo says it doesn't hang together coherently and the rest is hand-waved away.
If it's true (per Systrom) that low right/left atrial filling pressures are ubiquitous in ME: why do we see chronotropic incompetence on exercise challenge? Shouldn't HR be higher than healthy controls? (To maintain or increase cardiac output in the presence of relatively fixed reduced stroke volume).
How might you have orthostatic intolerance, with demonstrable reduction in cerebral blood flow (per van Campen), without orthostatic hypotension (regardless of tachycardia)?
Cerebral perfusion pressure depends on mean arterial pressure and intracranial pressure (CPP = MAP - ICP). JVP is not going to be high in us by definition (low RA/LA filling pressures), so we can stick with ICP. ICP does not rise on standing - in fact the opposite. Cerebral blood flow is dictated by cerebral perfusion pressure, mediated by cerebral autoregulation.
So if we have shown from multiple studies (in ME, POTS and other conditions) that you can have OI and reduced CBF with unchanged MABP (and ICP even went down a bit), then it suggests that cerebral autoregulation is the thing that's determining reduced CBF on orthostatic challenge. As Jo says —
And in a way it cannot simply be preload failure because if that was the cause there should be a fall in blood pressure. It seems that blood pressure is maintained. Yet there are symptoms suggestive of cerebral underperfusion - presumably indicating constriction of cerebral vessels preventing the normal blood pressure perfusing the brain. I don't think there is any good account of why that should be, is there?
The other thing is that a high proportion of people with ME/CFS have OI yet do not show POT on testing. So there are good reasons to think POT isn't the real problem.
There is no coherent story that I can see. Either it is preload failure, but then to produce cerebral hypo perfusion with a normal BP you would need additional cerebral vasoconstriction and there seems to be no reason why, or it isn't preload failure after all but an inappropriate cerebrovascular regulatory response.
This may be nonsense but here's a starter for ten. What if it's an
appropriate cerebrovascular regulatory response?
Could there be an explanation that's essentially in reverse, that the neurovascular mechanisms are deliberately trying to slow flow down in the brain (capillaries) in order to extract more oxygen
as a metabolic compensation. That might leave things vulnerable with regard to the homeostatic mechanisms of orthostasis as you're now operating much closer to the danger zone of inadequate cerebral perfusion, with less safety margin.
The tachycardia may be an inappropriate response (in this context) that occurs in some who have either intact (rather than down-regulated) or otherwise dysfunctional sensors and effectors. Perhaps this takes effect regardless of peripheral low blood volume, low right and left atrial filling pressures — and those findings are a correlation but a separate issue. Or perhaps the low blood volume occurs as part of the brain-dictated compensation (trying to reduce MABP and CPP) but the brain's needs and the body's needs are then in contention.
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Altered brain perfusion and oxygen levels relate to sleepiness and attention in post-COVID syndrome (2024, Annals of Clinical and Translational Neurology)
Interestingly, we found in our patients that slower blood perfusion in the caudate nucleus and the putamen were associated with better visual attention. The TMT also evaluates processing speed, working memory and executive functions, that is, cognitive abilities linked to the dorsal striatum. Our findings could therefore indicate retained normal vasodilation or recovery from capillary damage, resulting in better TMT-B scores. Meanwhile, those with faster perfusion, possibly due to reduced oxyhaemoglobin or compensatory vascular reactivity based on reduced tissue oxygenation, fared less well on this task.
Brain Frontal-Lobe Misery Perfusion in COVID-19 ICU Survivors: An MRI Pilot Study (2024, Brain Sciences)
Reduced Cerebrovascular Oxygenation in Individuals with Post-Acute COVID-19 Syndrome PACS “long COVID” (2023, SpringerLink)
Cerebral hypoperfusion in post-COVID-19 cognitively impaired subjects revealed by arterial spin labeling MRI (2023, Nature Scientific Reports)
