What do we actually know about orthostatic intolerance?

[Jonathan Edwards]

Cardiac output can be low despite high HR under reduced stroke volume (which is what you'd expect with poor venous return). HR cannot fully compensate.

Yes, but cardiac output is not the issue, it is cerebral perfusion. If blood pressure is maintained then perfusion pressure for brain is maintained, so low cardiac output is not a problem for the brain. It will only be a problem for tissues with arterial constriction.

So, as you say, if brain perfusion really is to blame for symptoms then something else is going on, which might just as well be going on in people without tachycardia too.

 

[Jonathan Edwards]

I think everyone's in agreement that focusing on OI makes more sense than tachycardia?

Yes, but do we really have good evidence for that OI being related to reduced brain perfusion if we don't have a story for that that adds up? In an acute reaction to typhoid vaccine you feel awful and have to lie down, but there is no reason to think there is a shift in brain perfusion as far as I know.

 

[Utsikt]

But the association of OI with tachycardia without a BP drop suggests much more that the unpleasantness of standing or sitting up relates to the reflex tachycardia itself rather than any loss of brain perfusion.

My HR gets 20-30 BPM lower from very low doses of betablockers, but there is no noticeable difference in the amount of «unpleasantness» when sitting or standing.

The unpleasantness also kicks in a while after the HR goes up.

My hypothesis is that the increased HR is a downstream effect of something else going wrong. It could even be a measuring issue where a BP «sensor» is faulty in some way so it thinks the BP is too low and therefore increases the HR to try to compensate.

 

[InitialConditions]

My HR gets 20-30 BPM lower from very low doses of betablockers, but there is no noticeable difference in the amount of «unpleasantness» when sitting or standing.

Yes, was going to mention this. Propranolol lowers my HR but doesn't relieve my main OI symptom, which is a sort of heaviness in my chest when upright.

 

[Jonathan Edwards]

My HR gets 20-30 BPM lower from very low doses of betablockers, but there is no noticeable difference in the amount of «unpleasantness» when sitting or standing.

The unpleasantness also kicks in a while after the HR goes up.

My hypothesis is that the increased HR is a downstream effect of something else going wrong. It could even be a measuring issue where a BP «sensor» is faulty in some way so it thinks the BP is too low and therefore increases the HR to try to compensate.

Interesting that betablockers do not affect the unpleasant sensation. To me that further suggests that the problem of OI is not brain hypoperfusion. If tachycardia was an attempt to keep brain perfused then betablockers ought to make the situation worse.

In the POTS definition the BP is by definition not too low. So maybe something is responding to some other shift, like venous distension in the legs.

 

[ChronicallyOverIt]

There are different upstream failures — hypovolaemia, venous pooling, sympathetic overactivation — driving reduced venous return and therefore compensatory tachycardia.

I’ve tried looking in the past, is there even a way to measure hypovolaemia? These all seem to me to be the common pointed at reasons for POTS or OI but what are they actually based on? Can you quantify sympathetic overactivation?

then betablockers ought to make the situation worse.

I was told, albeit not sure if this right, that the beta blockers slow the heart to let it fill with more volume increasing cardiac output, but this doesn’t make much sense to me?

Personally mestinon helped my OI (maybe increased cardiac output) until I became extremely allergic to it randomly at month 11, insane rashes that only stopped from stopping the medication.

 

[ChronicallyOverIt]

Cardiac output can be low despite high HR under reduced stroke volume

Ah I think this is the reasoning I heard behind beta blockers from my above comment. That they increase stroke volume?

 

[InitialConditions]

Ah I think this is the reasoning I heard behind beta blockers from my above comment. That they increase stroke volume?

Yes, that's right. There's other stuff going on, but reducing heart rate allows it more time to fill and increases stroke volume.

 

[InitialConditions]

Interesting that betablockers do not affect the unpleasant sensation. To me that further suggests that the problem of OI is not brain hypoperfusion. If tachycardia was an attempt to keep brain perfused then betablockers ought to make the situation worse.

In the POTS definition the BP is by definition not too low. So maybe something is responding to some other shift, like venous distension in the legs.

Betablockers do seem to work well for some with PoTS. I was just giving my personal experience, which I know matches others with ME/CFS. I think some take betablockers simply because their tachycardia is out of control and that is very unpleasant, regardless of other OI symptoms.

EDIT: Removed confusing sentence.

 

[InitialConditions]

There was a Raj paper showing that betablockers can make things worse in PoTS, especially at high doses, because they reduce cardiac output too much and can increase fatigue. Lower doses were much more beneficial.

 

[Nightsong]

I’ve tried looking in the past, is there even a way to measure hypovolaemia?

There's the radioisotope dilution technique.

 

[Jonathan Edwards]

Ah I think this is the reasoning I heard behind beta blockers from my above comment. That they increase stroke volume?

Yes, but that only increases perfusion pressure to an organ if the increase in stroke volume is proportionally greater than the reduction in pulse rate. That isn't generally the case, except perhaps in very fast pathological tachycardias.

 

[Utsikt]

Interesting that betablockers do not affect the unpleasant sensation. To me that further suggests that the problem of OI is not brain hypoperfusion. If tachycardia was an attempt to keep brain perfused then betablockers ought to make the situation worse.

My cardiologist specifically warned me about not expecting any symptom improvements other than reduced HR and palpitations, because so many of his patients had been disappointed by not feeling better.

In the POTS definition the BP is by definition not too low. So maybe something is responding to some other shift, like venous distension in the legs.

How does BP work? Is it constant everywhere?

I imagine that if you create a closed loop of pipes with a heart connected in somewhere, the pressure might be higher closer to the output of the heart right after each beat? So you’d have a wave of higher pressure that propagates at the speed of sound in blood.

How would that system behave if a pipe is squashed? More pressure before squash and less after?

Or if part of a pipe is made wider (like with pooling)? Less pressure after?

What about gravity? Could that alter the pressure at the top if the pipes were stood up instead of lying flat?

 

[Felis Catus]

My cardiologist specifically warned me about not expecting any symptom improvements other than reduced HR and palpitations, because so many of his patients had been disappointed by not feeling better.

That's very interesting. I haven't heard of anyone else's cardiologist or prescriber being that honest.

All meds I've tried for POTS only reduced my HR with no symptom or functionality improvement.

 

[Jonathan Edwards]

How does BP work? Is it constant everywhere?

Things are quite complicated but BP is pretty much the same throughout the major arterial tree. Beyond that local arteries and especially arterioles in each tissue can constrict and reduce perfusion pressure and rate.

The pressure is highest immediately after contraction (systolic) and lowest just before the next one (diastolic). The pulse pressure difference is gradually blunted along the arteries so that tissue perfusion tends to be fairly constant.

The heart generates a pressure of about 3 feet of water for brain arteries standing up. In young fit people it may be closer to 2ft and this causes no problem. To have reduced cerebral perfusion with a reasonably normal blood pressure you need major obstruction or constriction of brain arteries.

Gravity will have some effect but it only seems to be important if blood pressure gets very low (below 90mm Hg (3'6" water) systolic at heart level.

 

[ChronicallyOverIt]

There's the radioisotope dilution technique.

Has this been done in OI, POTS, or ME/CFS?