Long QT syndrome? Dr Cheney's thoughts on heart?

[xrayspex]

Eeyore-oops I had written you a post about l-carntine and then I just remembered i was confusing it with cysteine ---which gave me bad headache, i cant recall what carnitine does but tried it couple times--i have hard time tolerating many chemicals and aminos have been tricky--but curious if you think carnitine sort of interchangeable then with zithromax

but anyway I am very intrigued about zmax in cfs and in myself. I also wonderd if the 500mg capsules were of a better quality than the pink 250mg tablet zpak.

 

[Eeyore]

@xrayspex

What Dr. Cheney is describing is actually that his patients seem to have a mild form of short QT syndrome - the opposite of long QT - although it can also be arrhythmogenic. QTc is basically the same as QT except that it is adjusted for heart rate. Your QT interval obviously increases as the heart rate does, so you adjust the QT interval for the heart rate to get a more standard number.

I have generally tended to be on the short side of the QTc interval range, usually still normal, and I've had a lot of arrhythmias over the years. I saw an excellent cardac electrophysiologist and carried a 30 day event recorder. I had frequent PVC's and PAC's, but these are usually benign unless the number gets very large.

I have also read that ME patients tend towards short QT. If that's true, then it might be logical that a drug like zithro would be beneficial for them because it prolongs QT and also because of how it does so. This is speculative - not something you should run out and try - but there is possibly some reason to consider that it might be a useful treatment. If it were tried, it should be tried by a doctor who is monitoring you by EKG to see if your QT interval starts out short, normal, or long, and how it responds to therapy. My QTc was entirely normal (about 415-420) when treated with high dose zithro for an extended time (500mg a day). It has a very long half life, so it builds up quite substantially, and if you assume that the half life is constant and does not vary with concentration (it's not exactly) and is about 68 hours (which is the most often quoted number I've seen), that would mean that you'd have about 2.2g in your body at any time in a steady state model with 500mg daily dosing. That's a lot of zithro - and definitely not something I'm urging anyone to do. If you do it, do it with a doctor who is really watching it and paying attention. The long half life may explain why you experienced benefits for a while - it was still in your system. It can take around 2 weeks to get out of your system. Doctors love this aspect - it means fewer doses, sometimes just one, and not having to worry about patients stopping antibiotics when they feel better since they will be active in the body for a while after discontinuation.

If this is true, there are other ways to prolong the QT interval - but most people with true short QT syndrome (genetic, usually autosomal dominant) get an implantable cardioverter defibrillator. In true short QT syndrome, the QT interval does not change with changes in heart rate - I do not believe that is commonly the case in ME.

Re: the hypercalcemia and vitamin D, I think any effects of vitamin D on ME are likely mediated by the immune system. If ME patients all had major abnormalities of Ca++ metabolism, we'd know, as Ca++ is routinely tested for by many doctors, including primary care. Vitamin D that you take is not active - the body activates it in a regulated, stepwise fashion in the liver and kidneys. (Interesting to note that very high levels do cause hypercalcemia, and it's used as a rodent poison - but we are talking about levels far above and beyond what you are getting unless you're doing something really strange). Calcium is regulated by parathyroid hormone and calcitonin, the first increasing serum calcium, the latter reducing it, primarily by drawing from or depositing in the bone. Taking extra vitamin D - to a point at least - will not raise calcium levels much in the bloodstream. An extreme deficiency of course can cause problems. The body will pull from the bones, and you'll end up with rickets. The vitamin D receptor (VDR) also binds activated vitamin D (aka calcitriol).

Carnitine is part of the "carnitine shuttle" used to transport certain fatty acids across the mitochondrial membrane from the cytosol. Carnitine is essential for beta oxidation of some fatty acids (a fancy way of saying it breaks down fats to make energy, 2 carbons at a time, and which side it starts from), and a shortage of it prevents access of the mitochondria to fatty acids. It is called a shuttle because it is regenerated in the process. A fatty acid is attached in the cytosol to CoA to make an acyl-CoA. The carnitine binds the acyl-CoA, moves it across the mitochondrial membrane, where it dissociates (enzymatically catalyzed). Then the carnitine moves back to the cytosol to repeat the process - like a shuttle. This is hard to explain in words but looks very simple if you google a diagram (just look up something iike carnitine shuttle and then choose images in google).

There are a number of genetic deficiencies in this pathway that cause problems in fatty acid metabolism. I don't think most ME patients have them, but I do think there may be an acquired or partly genetic defect in fatty acid metabolism. You can have serum carnitine measured to see if you are low. It can be supplemented, but there have been a few recent publications that suggest that carnitine increases the population in the gut of certain commensal bacteria that produce TMAO (trimethylamine oxide), which can lead to atherosclerosis. Some doctors still actively promote its supplementation (e.g. Dr. Stephen Sinatra), whereas many also urge caution. It's a tough call. Personally, I had low carnitine, supplemented, and felt much better - but stopped, and felt worse, because of the risk of atherosclerosis. You can also look at acylcarnitines in the blood if the initial screen is low. This can show you which (short, medium, long, etc.) are abnormal - if any.

Interestingly, carnitine is synthesized from methionine (and some other stuff, maybe lysine?). It may be that people who build up homocysteine have a shortage of methionine, as homocysteine is normally recycled back to methionine. i.e. Carnitine deficiency, which has been anecdotally found with some frequency in ME patients (not sure if there is any peer reviewed research) could theoretically be due to a methylation defect, higher homocysteine levels, and ultimately lower precursors for carnitine synthesis. This is speculative, but plausible.

 

[xrayspex]

whoa, Eeyore you give a lot of food for thought, thanks! too brain fried to say much tonight after work.....but I did just discover this research---I discovered last summer when was given odasetron for nauseau that it combats oxygen hunger and I bet its because it prolongs QT, that must be what I need---I use it occasionally because it can help keep me going when need be and am sinking....hardly any side fx except constipation---which is not a good one tho ha
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202761/

 

[Eeyore]

@xrayspex

Ondansetron is a 5-HT (serotonin) receptor antagonist (specifically 5-HT3). Serotonin does play a role in gut motility (people with carcinoid syndrome make tons of it, and they get bad diarrhea and flushing) - so antagonism would be expected to cause constipation. It might be QT prolongation that gives you some benefit, but it could very well be a result of the action at the 5-HT3 receptor.

5-HT3 antagonists such as ondansetron also block the glycine site (an allosteric binding site on the NMDA receptor, an excitatory glutamate receptor in the brain). This is a form of non-competitive inhibition and it antagonizes NMDA receptor activity, which is generally a good thing in ME. You might benefit from other therapies that antagonize NMDA receptors. Mg++ is a natural NMDA inhibitor. After the NMDA channel opens (it's a cation channel, with modest selectivity for monovalent cations), cations flow into the cell. Eventually some Mg++ tries to get through, which clogs the channel, and closes it until it is reactivated. This is true for the other glutamatergic ion channels (but not G-protein coupled receptors). A number of prescription drugs block glutamatergic neurotransmission via NMDA channels.

Dr. Cheney has spoken about glutamatergic excitatory neurotoxicity for many years - he uses klonopin for it. Paradoxically, many patients feel more alert and think more clearly on small doses (per Dr. Cheney). This actually is GABA-ergic - but GABA and glutamate are generally in opposition in the brain, so augmenting GABA transmission often has similar effects to suppressing glutatmatergic transmission.

 

[xrayspex]

yea the benzos always too potent for me....but I get why they work for some with CFS. thanks again, I can see I will be spinning off into lot of research from yr post

 

[Forbin]

The absolute QT interval actually decreases as the heart rate increases (as you would expect). The QTc, which is calculated by different methods, provides a standard value relative to the 60 bpm value, regardless of heart rate.

In 2013, the FDA issued a warning about azithromycin which said:

FDA is warning the public that azithromycin (Zithromax or Zmax) can cause abnormal changes in the electrical activity of the heart that may lead to a potentially fatal irregular heart rhythm.
http://www.fda.gov/Safety/MedWatch/...tyAlertsforHumanMedicalProducts/ucm343350.htm

In 2014, a study of nearly 2 million veterans found that both azithromycin and levofloxacin (Levaquin) produced an increased risk of cardiac arrhythmia and death compared to amoxicillin. Levofloxacin's increased risk was somewhat worse than that of azithromycin.

CONCLUSIONS:
Compared with amoxicillin, azithromycin resulted in a statistically significant increase in mortality and arrhythmia risks on days 1 to 5, but not 6 to 10. Levofloxacin, which was predominantly dispensed for a minimum of 10 days, resulted in an increased risk throughout the 10-day period.
http://www.annfammed.org/content/12/2/121.full

There is always a balancing act between the risks and rewards in the use of any medication, but such an evaluation can only be made if the risks are well appreciated by patients and physicians.

A risk like QT prolongation has to be assessed not just in terms of a single drug, wherein the risk may be quite low, but also in terms of contraindications such as low electrolytes (e.g. potassium and/or magnesium), pre-existing QT prolongation, and the administration of multiple drugs, some of which may also contribute to additional QT prolongation as a side effect.

 

[Eeyore]

@Forbin

Yes thanks! The QT interval obviously decreases with increasing heart rate, not increases. Sorry about that.

 

[xrayspex]

Thanks you guys, you all have good info. I had hoped I wouldnt have to focus on this so intently again because its been a couple years since my symptoms in this domain really concerned me.but it does seem something odd happend with azithromyocin tht i really hope calms down once it is out of my system. The first 3 day 50mgdose I took in early March for pneumonia, I could tell it did something to increase my fatigue for about a week ( i was surprisingly still mobile for pneumonia) but then like I said a week or so later I thought it was a miracle drug because my energy was closer to my current baseline again plus I had less pain than in years and my brain seemed to be functioning better as well as my mood.

I started to get a headache though after another week or so and was convinced I should get more to keep the new improvements going--easy to justfiy because my dentist and I arent sure if some tooth pain i have is infection or cavity so she gave me precrip for Z because it decreased tooth pain first time, the 5day version this time. Finished it about a week ago and have been having heart palps intermittent, heart hurt a bit, oxygen hunger (more than in few years) killer headaches that are worse when lying down (I went thru that a couple times between 2006-2012 where have periods of what I think was intracranial hypertension that sometimes lasted for anywhere from few weeks to almost year that I think were precipitated by trying certain meds such as cymbalta), and my brain and mood is getting foggier again. I am not willing to take gamble that it means I need to try to take Z for along time- I didnt like some of the gut and couple other side fx this time . I am really really hoping that it is just temporary and once it is out of my body more this headache that is worse when lie down gets better.I also have c-spine issues that complicate figuring things out but I havent had this bad headache that is sensitive to position for quite some time, it seems sort of like a pressure builds up, and my face looks more bloated to me the last 2 days. So I suspect there is a cardiovascular component.

when i think back on it I think I have had some amazing help from meds that all have in common the QT prolongation, over the last 25 years I have had cfs/pain. At same time there also has seemed to be fine line where it goes from heaven to hell with those meds--and again that makes me want to try to dig up some old info from Dr Cheney where he wrote something about that in relation to heart---with the oxygen hunger---that there is some fine line where lying down makes most of us feel better most of time but then if the balance gets tipped too much then lying down can create uncomfortale symptoms in rare cases. and for me the QT prolongers sometimes buy me more time upright--until they do the opposite--I am guessing that there is small therapeutic window for me or something--i am really chemically sensitive. anyway, dang, wishing I would have left it at that one dose and not pushed my luck but was hard to resist because there were some really helpful aspect to Z--and still is, my overall body spine pain has been much lower the last 5 weeks-and well hopefully i will get over this heart/headache aspect and its just "healing crisis " as they used to say and then the benefit part will dominate again in a week....................I hope.

 

[Eeyore]

Keep in mind zithro remains in the body for a very long time. The half life is about 3 days - meaning if you take a pill, you still have half the zithro in your system 3 days later, 1/4 6 days later, etc. When you do a 5 day course, it continues to increase with each dose. Eventually it reaches a steady state where the amount being excreted is equivalent to the amount being taken, but that takes longer.

 

[xrayspex]

thanks Eeyore--I just reread that brilliant essay/interview Carol Sieverling did with Dr Cheney 10-15 years ago "Heart of the matter" and it lays it all out, what I am trying to recall--it rang true then and again now---and you tied in what he is talking about the connection with heart and Martin Pall with nitrous oxide and taurine etc--I know I am reinventing the wheel but its just uncanny to me how accurate it is yet there is no good consistent solution for a lot of folks and I dont think much follow up happened on Peckermans study related to that.

Anyway here is link to interview and in part 2b it describes that tricky balance between feeling better being up or liedown:

http://www.dfwcfids.org/medical/cheney/heart04.part2b.htm

"Now, here is a Congestive Heart Failure curve. [Curve C] Those patients are treated with Lasix to make them eliminate the extra volume, and then they are able to move up the curve and improve their cardiac output. "Most of you, on the other hand, need volume, and as we give you more volume you will come up onto the peak and will maximize your cardiac output. But, if we overshoot, you're going to go down the other side and you actually lose volume. And if you keep going down you'll actually go into heart failure."

" It's critical to understand the Frank-Starling Curve of Cardiac Output, where you [the PWC] are and how to manipulate it. [Notice that the healthy hearts in the diagram (curves A & B) have little to no drop after their peak!]
But, what if you're one of the ones right near the top of the curve and you increase your volume (preload) 2 liters by lying down? You could actually go over the peak and down the other side. Do you know what that means clinically? Some patients can't lie down! Some tell me, "When I lay down I cannot rest well or sleep." They went right over the top and dropped their cardiac output by lying down!"

In part 2a he talks about nitric oxide etc and warns in this interview against certain meds like provigil because it pushes cfs person too far and creates that out of balance (crash) and that is what I suspect, for me, that azithromyocin is sort of like taking provigil or even coke etc--it helps in a way but hurts in another way--and me, never could get relief from: magnesium vit b12, Pall protocol, richs protocol etc my whole chemical deal isn't working right so maybe my glutathione etc I just cant process zithromax properly or something -

-excerpt part 2a: "Which brings me to the most important statement I'll make about this peroxynitrite diagram. If you are immune-activated from virus, bacteria, mold, and/or toxin exposures, then you're generating an excess amount of nitric oxide. And if you also make a significant amount of ATP, it can result in superoxide, which then binds with the nitric oxide to produce large amounts of peroxynitrite. Then you're set up for major problems. [Oxygen transport, microcirculatory impairment, lack of tissue perfusion, etc.]"

I suspect the Zithromax created peroxynitrite in me. I am probably explaining this all goofy because I was a sociology major and molecular biology out of my conception lol but Cheney makes it pretty laymen friendly.

that relates to your advice then about reduce nmda eeyore--and I guess that is what I was thinking is that for me its fine line, I think QT prolonging meds maybe reduce nmda too--i feel there must be connection chemically to the QT aspect as well as the Pall chemical theory--anyway---but then there is that fine line where its lengthening QT and reducing NMDA and then boom it goes too far in the curve, maybe per Starling or Pall theories and get other worse symptoms. from part 2b:

"Provigil does the opposite. Provigil does several things, but is mostly an NMDA-activator —it's a stimulant similar to cocaine—it will actually stimulate nitric oxide production. It may also stimulate ATP generation, which is the benefit perhaps that one sees. With more nitric oxide, you can think better, your memory improves, you can focus better, and you have more energy. But what you're doing is generating more peroxynitrite and this may not be felt for a while, but ultimately it's probably felt—in the brain at least—as Alzheimer's or Parkinson's Disease or worse, ten years from now."

How to Block Peroxynitrite

1) Increase CO2

Let's turn to peroxynitrite. According to the Textbook of Medicine, and Dr. Pall himself, what is your primary scavenger of peroxynitrite? The answer is CO2. Carbon dioxide. When ATP is generated in the mitochondria, CO2 is produced as a by-product. So, when you make energy [ATP], you produce the very thing needed to scavenge peroxynitrite. It's a beautiful system! When everything works perfectly, you can make a lot of ATP because superoxide is being broken down into water. And CO2 is produced which will get rid of any peroxynitrite that accidentally happens to be produced.

What a great system! If that system could be maintained in the state it was in when you were born, you should live to 120 to 140 years of age. It's just that things creep in that degrade that operation, that system, and we just exit out earlier than we should.

Now, if you keep lowering ATP production, which then reduces the amount superoxide produced, you also reduce the production of CO2. "The result is you have less and less primary defense against peroxynitrite. It's a vicious cycle. And especially in the lowest energy states of all you really have that problem."

How do you increase CO2? Well, first let me ask how you decrease CO2, which we definitely don't want! Hyperventilation. If you hyperventilate, you dramatically decrease CO2, which would be highly damaging. It can produce carpal-pedal spasms in some patients (carpal: wrist; pedal: foot). Its most damaging effect is to your brain, however."

then article goes on to recommend bunch of naturalish ways to increase CO2 which have only been at most mildly helpful for me over the years. That said if I wantd to go walk a mile right now I could, am more lethargic than usual but able. altho lack of sleep isn't helping either, cus can't sleep in upright position well which keeps this headache at bay.

anyway wanted to document this all to help remember all the connected dots so that when I forget again in a year I can hopefully find it at PR again.

I think that is why ssri's and some snri's like cymbalta etc have that doubleedge for cfsish folks---its like the risk of cocaine per Pall's chemical explanation.

 

[Eeyore]

@xrayspex

Interestingly, my ME specialist warned me about provigil too. Also, my genetics suggest it won't work for me. However, it has been one of the most helpful meds I have taken! Go figure. I've been on it for almost a decade w/o adverse effects or a greater crash tendency. In some studies (not specific to ME patients) provigil has been found to be protective against Parkinson's. It's also used in the treatment of Parkinson's.

I don't think zithro is related to glutathione. It likely works via one of 3 mechanisms. First, it is antibacterial (obviously). Second, it binds to the hERG potassium channel in the heart, prolonging the QT interval. Third, it has immunomodulatory effects.

There is no direct connection between meds that prolong the QT interval and those that block the NMDA channel. I do not believe zithro has any effect on the NMDA channel.

If zithro affects ROS generation, I'm not sure how. Conceivably, it could enhance the respiratory burst in neutrophils / macrophages, but I don't think so. I believe that actually zithro tends to reduce ROS generation by altering the lysosomal pH - but I'm not sure now - I remember reading that. It works in a way that is similar to chloroquine in macrophage lysosomes - there was a paper on that on pubmed.

I have never had a good reaction to any serotonergic drug. Every one I have tried has been very poorly tolerated.

Interestingly, I had a stretch in one very bad relapse where my blood CO2 was extremely low (11ish) and always out of the range of normal. In periods where I've felt better it's generally been higher. The normal medical explanation for low CO2 is either metabolic acidosis or respiratory alkalosis (you need to measure blood gases to know which one). I had a high anion gap - suggesting the presence of some anion not measured. I don't have a good answer for that. My CO2 runs mostly low normal now.

Inosine or, even better, isoprinosine is often found to be beneficial in ME patients. If you take inosine (the cheap OTC supplement) be aware that it's not dosed the same as isoprinosine. I worked out the chem once and isoprinosine only has about 1/4 or so the inosine on a weight/weight basis. If you take the same amount of inosine as you would isoprinosine, you'll probably get hyperuricemia and maybe gout (excess urate builds up and is insoluble - it can deposit to form urate crystals, and that is gout). Kidney stones are also a risk. If you do try inosine or isoprinosine, you should do it with a doc and have serum uric acid levels measured. Cheney believes the mechanism is that it scavenges peroxynitrites - but this is untested/unproven in any published studies.

Edit: A 4th mechanism for zithro might be alteration of the gut microbiome.

 

[xrayspex]

thanks eeyore, yea I am sleep deprived from this flare, and obsessed cus in flare, bad combo oh bad trio cus add in the no-science education background....so throwing around concepts loosely. but yet there is so much in that cheneyinterview/explanation that just fits altho I may not totally get the tech reasons behind it all.

I tried provigil one summer, and the first week it was brilliant and then it went bad, I tried pulsing with tiny doses but everytime, after it went bad for me, I would get bad effect, particularly striking was on my eyes--light just burned, i had to wear shades a lot . a month after the last dose my eyes calmed down mostly altho i did get diagnosed with sjogrens after that I suspect it irritated the autoimmune stuff. It was great at first for energy, mood, andpain reduction, but eventually it practically gave me anhedonia which took like month to wear off, had to put on act but didnt really want to engage.
there are different reasons people get what is called "cfs" thus different things work for different folks eh. I thouht cymbalta and tramadol were brilliant too very briefly til they became my nemesis. Part of problem for me could be some of the tests like by genova etc show I have problem in phase 2 of detox and genetics show probs with cytochrome p45o. particulalry cyp2d6--which is interesting given how well i tolerate odansentron--but most things no.

so in part 2b say if you accept his premise that for some folks part of problem is as pall says and want to reduce nmda, nitric oxide, increase gaba etc and that is why certain subset of cfs shouldnt take provigil or coke or ssri's etc because they activate nmda etc and that worsens cfs. here is what i dont understand, if CFS is a problem with physical and mental brain fatigue etc and its a problem responding well to lowering nmda--

and then stimulants which for a lot of folks improve brain and physical activity but they also activate nmda --are bad for most cfs because want to reduce nmda in cfs


why does CFS which is low energy share in common with stimulants (high energy) a state of activated nmda etc-------one would think intuitively that increasing energy thru chemicals known to do that would improve energy inlow energy humans--but in cfs you want to do the opposite, sort of sedate like with klonopin or gabapentin to get more energy output thru reduce nmda
He talks about all that at beginning of part 2b
http://www.dfwcfids.org/medical/cheney/heart04.part2b.htm

 

[Gingergrrl]

"Now, here is a Congestive Heart Failure curve. [Curve C] Those patients are treated with Lasix to make them eliminate the extra volume, and then they are able to move up the curve and improve their cardiac output. "Most of you, on the other hand, need volume, and as we give you more volume you will come up onto the peak and will maximize your cardiac output. But, if we overshoot, you're going to go down the other side and you actually lose volume. And if you keep going down you'll actually go into heart failure."

It's critical to understand the Frank-Starling Curve of Cardiac Output, where you [the PWC] are and how to manipulate it. [Notice that the healthy hearts in the diagram (curves A & B) have little to no drop after their peak!] But, what if you're one of the ones right near the top of the curve and you increase your volume (preload) 2 liters by lying down? You could actually go over the peak and down the other side. Do you know what that means clinically? Some patients can't lie down! Some tell me, "When I lay down I cannot rest well or sleep." They went right over the top and dropped their cardiac output by lying down!"

@xrayspex Interesting quote from Cheney and I broke it into paragraphs just to make it easier to read. I am curious if you or @Eeyore have an opinion on something for me re: this quote. In general, I have low BP and am told that I have low blood volume (but no formal test for this.) I get constant shortness of breath walking or with exertion but absolutely no breathing issues when I am lying flat or even sitting.

I am not sure what the Frank-Starling Curve is but think I understand the concept from the quote. My question is, back in Nov I had three attempts at IV saline and on the third attempt (one liter of normal saline infused over three hours with magnesium) I had a reaction which sent me to the ER and my doctor later interpreted it as "flash pulmonary edema" although the ER did not run any tests to capture what was happening in the moment.

I do not have congestive heart failure and all my Echos and other tests are perfect (no diastolic dysfunction, normal ejection fraction, no ventricular stiffness, etc.) What do you (hypothetically) think Dr. Cheney would make of this?

 

[IreneF]

@xrayspex
The headache that gets worse when you lie down, plus tooth pain in the upper jaw, sounds like inflamed or infected sinuses. (Dr. Montoya thinks CFS/SEID is an inflammatory disease, so it would make sense from that perspective.) I have a chronic headache with post-nasal drip. I keep my sinuses from getting infected by taking a generic Claritin daily. If I had more energy I would try a neti pot.

 

[xrayspex]

GingerGurl--hopefully others will articulate to your question-but yea most CFS folks don't get diagnosable heart disease and I think Cheney says in the interview that CFS is sort of actually a protection from getting fullblown heart failure, if you read parts 1a thru 2b its very educational.

-but that is also interesting, your experience with saline...I tried iv saline in the 90s, had a doc locally back then who was FM doc and innovative and some CFS/FM folks here got and maybe get a lot out of those regular IVs--I didnt like it--I just looked bloated, my face all puffy from all the water but I didnt really feel any better so was not worth it. My doc didnt know what to make of it. but again with these sort of health problems, there is so much individual variation. I think it ties into what I was saying is that for some of us maybe there is just too tiny of window of medicinal effect with some treatments that just a tinch too much of something and it goes from bad to worse but sometimes if you find the sweet spot,for a little while, you feel better. so many CFs people report certain things will work well for them for a while and then stop working. that happened to me with gabapentin for example (among a bunch of other things--like maybe the zmax for me)

I think your experience with saline is going too far the other way--like lying down makes most CFS people feel better unless the go too far on that Starling curve--and I think that is tying into my discomfort the last few days--I went the other way and am retaining too much fluid or something causing pressure headache--it even feels like hands are swollen altho they dont look that different, but i am very in tune with body

thanks for breaking it into more readable parts, I will go back and try to do that in origninal, iget too tired and lazy to be good editor, esp when excited to write it all

but anyway read carefully that whole interview with Cheney because he addresses that about how people can go from feeling better to feeling worse with lying down sometimes, maybe someone can explain Starling in more depth than he did in that essay--but i suspect your problem is something to do with Starling curve, its detailed in part 2b
http://www.dfwcfids.org/medical/cheney/heart04.part2b.htmt:

he also gives a lot of tips for natural ways to deal with the cardiac and chemical problems.

and thanks Irene for thought about sinus and tooth--those are very suspicious to tie into my problem right now too, I agree

 

[xrayspex]

well yay, update, if i get a good nights sleep I am feeling the better than usual thing again post-zithromax, less pain, more optimisim, energy not bad relative to my regular baseline....will see how long this lasts I am thinking there is a sort of herx while taking zith that lasts for awhile and then as it dissipates out some get to reap the benefits for a bit