ramakentesh

In some studies hyperadrenergic presentations and low flow states correlated with the lowest blood volume - meaning that in most cases low blood volume is a feature of more hyperadrenergic presentations. In my case Florinef lowered my standing BP and HR. One thing to remember in POTS specifically is that 'blood pressure' measurements only measure arterial pressure. Usually when arterial pressure is elevated, so is elastic recoil in veins. True hypertension is associated with hyperdynamic circulations, increased cerebral blood perfusion, increased cardiac output and stroke volume, increased overall blood volume and kidney vasoconstriction. Most of the damage done by chronic hypertension is caused by it being continually increased - even lying down. In POTS there is mostly reduced venous return, reduced stroke volume and abnormally/impaired cerebral blood flow and autoregulation - and the arterial pressure goes down when patients lie down. In other words there are none of the actual main risk factors of essential hypertension. Some may even have an arterial sympathetic overshoot to compensate for impaired cardiac refill and stroke volume. Im not suggesting that walking around all day with arterial pressures of 170/100 is a healthy thing or not something to be concerned about, but arterial pressures in POTS themselves may not be showing people a true picture of the underlying hemodynamics.

Im not convinced that excessive norepinephrine or impaired norepinephrine reuptake causes POTS or that it can be caused chronically from taking an SNRI that is then stopped. The short answer to your question is that its unknown what causes POTS although there seem to be some interesting associations - small fiber neuropathy in some, impaired NET and NE clearance in some, but nearly always reduced venous return to the heart and reduced stroke volume which would not suggest a state of increased NE mediated venoconstriction.

There are actually nearly no longitudinal studies in POTS, there is currently no agreed delineation or phenotypes within POTs, and most of the suggested underlying causes are equivocal and have not been replicated in multiple studies.d When a doctor tells you that patients get better within a specific time frame he or she is basing this either on their own clinical experience (anecdata) or from review documents that have little supporting evidence. The truth is this is probably unknown. When a doctor or a patient diagnoses a patient with 'hyper' POTS all they are doing is describing a presentation rather than a separate etiology: https://ww2.mc.vanderbilt.edu/adc/42008 Over the years Ive noticed some patients get one long boute of POTs and then recover. Some relapse after decades. Some relapse and remit over and over. Some relapse and remit and slowly get worse. Some are always the same and never improve and sadly a small minority stay bad and gradually get worse.

Blood pressure measurements are almost meaningless in POTS because they are arterial measurements - they do not tell you anything about what your veins are doing - is there pooling? Is there inadequate venous return? Increased microvascular filtration? Try looking at pulse pressure when symptomatic. That may tell you more. Narrowing stroke volume is a good measure of reducing stroke volume from inadequate venous return.

I hear this reported for Midodrine quite a bit. I take only when needed rather than constantly to avoid tolerance to it. Secondly I cycle my medications so that my body doesn't get used to them. Another virtually identical medication is Phenylephrine which is in Sudafed PE and is also an alpha 1 agonist although it is hampered by poor oral bioavailability. When I am symptomatic I usually take either phenylephrine or midodrine and then the opposite the next day. And then on really bad days I take Pseudoephedrine. Seems to stop the body getting used to the medications. Doctor approved ofcourse.

I think biofeedback is as likely to be more than a placebo at about the same level in POTS as it would be in essential hypertension or MS.

Low central ne = high glutamate

Provigil/modafinil helped a little with this but for me pseudoephedrine is superior and it actually lowers my heart rate. I dont actually agree with vandy on this - i tend to believe there is impaired central norepinephrine activity (which by reciprocal association) causes peripheral norepinephrine overactivity. Pots patients generally seem to show evidence of increased norepinephrine with symptoms of hypotension.

There is lots of work evaluating yhe roke and functional impact of autoimmunity in POTS. There is a study attempting to demonstrate that small fiber neuropathy translates to wider vasomotor nerve involvement. There is a trial on droxydopa in pots. There is also people looking at brain changes in OI.

This symptom seems related to the ineffectual attempts the body makes to adjust for reduced cerebral perfusion. the body attempts to rely on beta receptor activation and ramps up sympatgetic activity to compensate for impaired sympathetic vasoconstriction. it is also possible that there are central abnormalities in norepinephrine and dopamine regulation in some patients. Serotonin could be at play but I suspect fatigue is centrally mediated from reduced norepinephrine or dopamine release the former which is centrally calming and is intimately involved in governing levels if glutamate and perhaps nitric oxide.

Dr Julian Stewart described a subset of POTS designated low flow that had resting vasoconstriction. However most pots patients have decreased venous return and although some do have (at least according to older studies) cerebral vasospasm. Initially i had a 'hyper' presentation but over time it morphed into a more neuropathic presentation especially once i corrected the low blood volume.

Can certainly happen (fluctuating symptoms are fairly common) - has yoir doctor talked about Midodrine or Droxydopa in your case?

My symptoms cone and go in a seasonal cycle

So some get it from MCAD and some like me get it from SFN

I agree with Katybug

Its still a bit of a way off but a smaller one will come out any day.

I generally find personally that i tolerate other vasoconstrictors better than midodrine

Yeah i flare and remit on and off since 2003

Yeah my fatigue has got worse over the years

As a dude i can vouch its better to remain horizontal

Most patients probably fit a variety of 'subforms' - mast cell disorder, small fiber neuropathy, hypovolumia and hyperadrenergic features. Its a spectrum rather than clear groupings

https://www.mc.vanderbilt.edu/root/vumc.php?site=adc&doc=42008

Honestly this is so exciting and yet so obvious

And there it is. Game set and match. I was already about 90% certain my condition was caused by 'local interference' of alpha 1 mediated vasoconstriction with compensatory overactivity of the general sympathetic nervous system. My general belief is that its specific to alpha 1b subgroup and as a consequence some vasoconstrictors work better than others. ive been pushing for research into autoimmunity beyond the acetylcholine receptor autoantibodies since 2005 due to the overwhelming evidence that pots is autoimmune in some patients (acute onset, fluctuating course, female to male ratio). Its also important to note that kidney alpha 1 receptors may be involved in sodium retention. congrats to dys int and Lauren Stiles for facilitating this discovery and Dr Kem and Dr Raj for their work. in the words of an important POTS researcher - autoantibodies are here to stay (in pots research).

Yes and its easy to explain. It impairs norepinephrine mediated vasoconstriction as occurs in migraine afterglow