Effect of lower body negative pressure on cardiac and cerebral function in [POTS]: A pilot MRI assessment, 2024, Skow et al

Effect of lower body negative pressure on cardiac and cerebral function in postural orthostatic tachycardia syndrome: A pilot MRI assessment

Abstract
Postural orthostatic tachycardia syndrome (POTS) is characterized by an excessive heart rate (HR) response upon standing and symptoms indicative of inadequate cerebral perfusion. We tested the hypothesis that during lower body negative pressure (LBNP), individuals with POTS would have larger decreases in cardiac and cerebrovascular function measured using magnetic resonance (MR) imaging.

Eleven patients with POTS and 10 healthy controls were studied at rest and during 20 min of −25 mmHg LBNP. Biventricular volumes, stroke volume (SV), cardiac output (Qc), and HR were determined by cardiac MR. Cerebral oxygen uptake (VO2) in the superior sagittal sinus was calculated from cerebral blood flow (CBF; MR phase contrast), venous O2 saturation (SvO2; susceptometry-based oximetry), and arterial O2 saturation (pulse oximeter). Regional cerebral perfusion was determined using arterial spin labelling. HR increased in response to LBNP (p < 0.001) with no group differences (HC: +9 ± 8 bpm; POTS: +13 ± 11 bpm; p = 0.35). Biventricular volumes, SV, and Qc decreased during LBNP (p < 0.001). CBF and SvO2decreased with LBNP (p = 0.01 and 0.03, respectively) but not cerebral VO2 (effect of LBNP: p = 0.28; HC: −0.2 ± 3.7 mL/min; POTS: +1.1 ± 2.0 mL/min; p = 0.33 between groups). Regional cerebral perfusion decreased during LBNP (p < 0.001) but was not different between groups.

These data suggest patients with POTS have preserved cardiac and cerebrovascular function.

https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15979

 

Haven't read the paper yet. Oddly I was thinking about upright MRI vs lower body negative pressure in supine MRI just yesterday.

Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety (2007, Journal of Applied Physiology) compared POTS and HCs at 0, -10, -20, -30 and -40 mmHg, also with shams. They looked at HR/BP and not cerebral blood flow.

 

Does lower body negative pressure have the same physiological effect that being upright does?

 

According to the study not in this group of people, simply because allegedly the POTS patients are supposed to have POTS and the healthy controls don't but no differences were seen in the LBNP setting, including BP measurements (the alternative explanation would of course be that "POTS" defined as BPM increase during tilt-testing is not a meaningful characterisation of anything or that the study wasn't run well). The study mentioned above by @SNT Gatchaman does however find a correspondence (at least at -40mmHg, not sure about higher pressures since here the measurement is at -25mmHg).

It would have been very interesting if this study also had a tilt-test+celebral blood flow measurement arm.

 

They didn't satisfactorily generate POT in the POTS patients, so I don't think they can conclude with "the symptoms observed in individuals with POTS may not be driven by significant cardiac or cerebrovascular dysfunction."

But

The patients and controls were 17-18, near exclusively female. The HCs didn't have +30 BPM with active stand challenge. There's still a possibility some of the HCs had subclinical OI. Ideally you could exclude this with tilt and transcranial Doppler US (or NIRS).

 

One thing do not understand is that people with 'POTS' are supposed to be at risk of low cerebral blood flow. Yet, if the BP is maintained (as it is by definition in POTS) and the heart rate goes up there is no reason why the brain should get less perfusion. It might get more.

 

Could it not be the other way around. Perhaps, when upright, the brain gets less perfusion in people with POTS for whatever reason and so heart rate increases to try and address this. While this might help normalize cerebral flood flow for a little while, eventually it won't be able to keep up.

If blood is pooling in the extremities could overall blood pressure remain the same but less blood be reach specific areas (like the brain)? Also not sure how how something like preload failure would impact on blood pressure but it seems to be found in POTS.

I have POTS and it certainly feels like my heart is struggling to get blood to my brain when I am upright for longer periods of time. It also explains why some people with POTS pass out after standing for too long.

 

Blood flow to an organ depends only on average blood pressure and vessel calibre. There is no obvious reason why people with POTS should constrict brain vessels on standing so the only relevant change would be change in arterial pressure. Brain venous pressure would go down on standing which would help flow if anything. So, in terms of accepted physiology there is no reason for less brain perfusion if blood pressure is maintained, as it is in POTS.

I have always thought the terms 'preload' and 'after load' were dubious buzzwords better avoided. Preload is used to refer to the availability of blood in central veins to flow into the heart to allow it to be pumped on to tissues. That does not affect the equations at all since the actual amount of blood reaching the tissues depends only on the arterial pressure - which we have said is normal - (and vessel contraction in the tissue).

Reduced availability of blood from central veins (preload) could trigger vasoconstrictive signals and it does during shock producing cold hands and feet but I am not aware of it constricting brain vessels. Again, if there was constriction in peripheral tissues like hands and feet that would favour normal or increased brain perfusion.

It may well be that POTS is a term often used for situations in which arterial blood pressure does fall as well as heart rate rising.

 

Independently of blood pressure am I wrong in the assumption that most healthy people have a resting heart rate of around 50-80 and a standing heart rate of around 70-110? So many people will naturally have a BPM increase of somewhere around 30BPM between lying on the floor and standing leaning against a wall? Or is this really that abnormal?

 

I do not know the literature but I have seen it commented that a rise of 30bpm is not necessarily abnormal.

 

Wouldn't that be sufficient evidence that automatically implies that POTS (if there isn't a blood pressure drop)/Orthostatic hypotension (if there is a blood pressure drop) are rather senseless diagnostic labels in the general population, at least if one uses the NASA lean test, because an increase of 30bpm shouldn't automatically lead to a medical diagnosis if there is in fact nothing that might be wrong?

 

My guess is that you have to have symptoms first. If you feel bad on standing and that is associated with a 30bpm rise and no blood pressure fall then it gets called POT. If blood pressure falls it is called orthostatic hypotension.

This may seem unjustified but there are other examples of something similar. If you have nasty pains in the big toe at night with redness and your rate level is above 0.45 you can be reasonably diagnosed with gout - i.e. it is highly likely that the pain is due to rate crystals. But quite a lot of men have rate levels above 0.45 and never have gout.

Nevertheless, I have never had enough experience of the area to really judge whether POT is a useful term. I had never heard the term used in my career as a physician until I got interested in ME and joined forums. If it is anything like 'mast cell activation syndrome' it probably has no real basis as a specific entity. But there may be a small number of people who have a specific haemodynamic problem that fits POTS. My reading of the ME literature is that the OI of ME probably isn't POT in the great majority of cases.

 

How about if in people with POTS the brain vessels do not sufficiently dilate to ensure that blood flow remains stable? I presume there are very many mechanisms to ensure sufficient CBF in healthy individuals when standing. Given that CBF needs to remain within a pretty tight window, it seems like even small issues could result in significant problems. One question, why do significant G-forces result in insufficient CBF. Do G-forces change the overall blood pressure in the body because it seems to be a similar situation as to what happens in POTS?

I am not necessarily a fan of the term either, just like I am not a fan of the term neuroinflammation. However, I think the concepts behind these terms are interesting and worth exploring. The only reason I brought this up is because there are clearly patients with POTS where insufficient blood is getting back to the heart. What effect that would have on CBF and other parameters I do not know. However, I agree that the arterial pressure is more would seem to be the important factor is determining the amount of blood reaching tissues.