Small Vessel Dysfunction?!!

[anna]

I have been thinking again Yes I know not a wise thing uses up too much energy!! LOL

Back to my idea about Dysfunction in the microcirculatory system due to Ehlers Danlos syndrome's weakened collagen. I found the following interesting!

Small vessel disease symptoms include:

• Chest pain, squeezing or discomfort over your central or left chest
  
• Chest pain associated with discomfort in your left arm or jaw
  
• Chest pain that worsens with activity, though eventually it may occur at rest too
  
• Neck, shoulder, upper back or abdominal discomfort
  
• Shortness of breath
  
• Unusual fatigue
  
• A lack of energy
  

[anna]

http://www.uptodate....source=see_link

The coronary microcirculation, which consists of resistance arterioles, capillaries, and small veins or venules, plays a major role in the delivery of blood and nutrients to the myocardium. In addition to its physiologic role, the coronary microcirculation is affected in a variety of systemic and cardiac disorders. These may be considered functional alterations, involving changes in the responsiveness of the coronary microvasculature, and structural effects, as with alterations in the number and diameter of the coronary microvessels. While much of the microvascular vasoregulation occurs due to metabolic and autoregulatory factors, microvascular tone and, hence, myocardial perfusion, is also influenced by the vascular endothelium.

ENDOTHELIAL DYSFUNCTION

Endothelial-mediated vasodilation is abnormal in a variety of pathologic conditions, including atherosclerosis, hypercholesterolemia, diabetes, hypertension, cigarette smoking, ischemia reperfusion, and aging. (See "Endothelial dysfunction".)

The mechanisms underlying these abnormal endothelium-dependent responses include:

• A reduction in the synthesis and release of nitric oxide (NO), resulting in part from deficiencies in L-arginine, the substrate for endothelial nitric oxide synthase (eNOS), and the co-factor tetrahydrobiopterin.
  
• Abnormalities of G-protein signaling, resulting in reduced activation of eNOS in response to endothelial cell receptor activation. In addition, the enzyme arginase may be increased in activity after ischemia-reperfusion, decreasing the available L-arginine [1].
  
• In some of disease states (eg, hypercholesterolemia, hypertension, and diabetes), there is increased vascular production of superoxide, which reacts rapidly with NO, leading to the formation of the toxic peroxynitrite anion. While peroxynitrite can produce vasodilation, it is a weak vasodilator; as a result, much of the vasodilator capacity of NO is lost.
  

Although the initial studies demonstrating abnormal endothelium-dependent vascular relaxation in various disease models were performed in larger vessels, subsequent experiments showed that most, if not all, of these disease processes affect the coronary microcirculation in a similar fashion.

I have seen lots of threads on Nitric Oxide does the above have any connection to NO in POTS research?!

[ramakentesh]

Yeah prettymuch describes the findings similar but not the same to LOW FLOW POTS and perhaps the studies coming out of China or Japan on POTS suggesting that elevated hydrogen sulfide (a molecule that plays a role in microvascular dilation) have been found in some of us POTSies... Endothelial disfunction is being implicated as a major player in a large subset of patients - whether its eNOS, reduced NO bioavailability, reduced nNOS or increased constitutional nNOS (neuronal nitric oxide) and ultimate derangements in superoxide and ROS.

Vandebilt are doing a study on endothelial function in POTS now.

I dont really the connection between altered endothelial health, eNOS, nNOS and collagen...

[ramakentesh]

Also there is a study saying that a cohort of CFS patients - approx 25% of which have POTS according to a recent study - have increased microvascular vasodilation in response to normal acetylcholine activity.

[issie]

As for the connection with EDS and NO - not sure. But, I have been using 250mg of l-arginine in the a.m. for about a month now and I'm doing better. In fact, I just went for a snorkel trip and was able to swim for about 2 hours. This is a major accomplishment for me. I started getting tired and my tachy started up when that happened. But, the l-arginine is helping my blood flow and oxygen levels have come up and so has my energy. This is the first thing I've used that has seemed to help. I'm HyperPOTS and suspect have low NO levels. (Long story - see other threads.) I've also started using grapeseed oil and that improves circulation too. And parsley which is a natural form of potassium. It's odd to me because you'd think there would be too much laxity of the veins with EDS. But, in my case, it seems to be just the opposite - too constricted. I really don't understand why because this would appear to be just the opposite of what one would think with the connective tissue disorder.

[anna]

Hello Ramakentesh, your input is interesting, I need to read more about Endothelial dysfunction.

Issie, it is very encouraging that the l-arginine is helping, I will go look again at your threads, I now have high BP not well controlled! but when young I had very low BP like my 3 children. It is all so confusing!!!

[anna]

Ok so might this be the connection:-

Endothelial cells form a single cell layer that lines all blood vessels and regulates exchanges between the bloodstream and the surrounding tissues. Signals from endothelial cells organize the growth and development of connective tissue cells that form the surrounding layers of the blood-vessel wall. New blood vessels can develop from the walls of existing small vessels by the outgrowth of endothelial cells, which have the capacity to form hollow capillary tubes even when isolated in culture. Endothelial cellsof developing arteries and veins express different cell-surface proteins, which may control the way in which they link up to create a capillary bed.

A homeostatic mechanism ensures that blood vessels permeate every region of the body. Cells that are short of oxygen increase their concentration of hypoxia-inducible factor 1 (HIF-1), which stimulates the production of vascular endothelial growth factor(VEGF). VEGF acts on endothelial cells, causing them to proliferate and invade the hypoxic tissue to supply it with new blood vessels.

[Lenna]

My son, who has low-flow POTS but is not hyperPOTS, is being tested for endothelial dysfunction. He had a biopsy done over a year ago as part of a clinical study looking at the effect of NO on POTS, and I've gotten the docs to agree to take a look at the endothelial cells in the biopsy. We've been waiting quite a while for the results, but hopefully will have them soon. I'll post here if I learn anything relevant.

BTW, he has an NO deficiency and has been taking Losarten for the past 10 months or so to boost up the levels and dilate his blood vessels. He is not "cured" but is so much better. He pretty much missed grades 10-12 of high school, but is now applying to college with the expectation and hope of being a successful student, perhaps on a reduced class schedule.

[juliegee]

Interesting thread! My rheumatologist surmises that I have endothelial dysfunction in my heart & lungs as well as my hands and feet. I have severe Raynaud's and often sport purple/black fingers and toes in the winter. I am unable to tolerate any of the traditional treatments. Here is a link that describes the connection between Raynaud's and endothelial dysfunction http://www.lef.org/protocols/heart_circulatory/raynauds_syndrome_01.htm

To corroborate her theory, In the cold months my BP rises and I often experience chest pain. My blood vessels clearly vasospasm in response to cold and stress. I had one echo that showed diastolic dysfunction (beginning stage of heart failure), but had a subsequent test that was normal. The way I understand it, endothelial dysfunction occurs when the vasospasm is sustained and hypoxia occurs- then the revascularization occurs. (Please correct me if I am misunderstanding this!) Perhaps the vasospasms have not been sustained enough to show endothelial dysfunction in my heart and lungs...yet.

So far this season, I have NOT experienced my typical BP rise, chest pain, nor sustained Reynaud's. The only thing I can attribute the improvement to is the addition of magnesium to my med regimen. I take 500mg every night. It relaxes my blood vessels and seems to prevent the sustained vasospasms both in my extremeties and in my chest

Very interesting to read about the connection between connective tissue and endothelial dysfunction, Anna!

[anna]

I was put on Losartan 8/9 years back due to Very high BP, my GP tried a combo of meds, and finally we stuck with Losartan and Amalodipine a calcium channel blocker, I had lots of what I now know is ANS issues going on at the prier to being put on the BP med's but Dr.'s just thought I was a little mad!!! well it is so odd that once on the BP meds my ANS stuff eased off allowing me to function, now I can see why that might have happened!!

Julie you may find this article quite interesting:

http://bloodjournal.hematologylibrary.org/content/91/10/3527.full

[juliegee]

Ooooh Anna,

A little light reading- yay! Seriously, looks very informative- THANK YOU. I will take my time to absorb. I find this whole thread very interesting. All of your posts are very thoughtful and insightful.

This overlaps with other research I have been doing, especially the part that relates connective tissue development to endothelial cell signaling. Connective tissue is also comprised of mast cells. When mast cells degranulate, vascular permeability is greatly affected to the point where it can actually lead to an aneurysm. There is a subgroup of us, who suffer with both connective tissue disorders and mast cell disorders as well as autonomic dysfunction. Many of us have personal history or family members with anuerysms/dissections. This dovetails nicely with that

Keep researching and sharing. It benefits us all!

Gratefully-

Julie

[anna]

I wish I had found that article some years back! It does seem plausible that there might be a hiccup some where along the line that interrupts the endothelial cell function.

Oh well more reading!!!

[Elegiamore]

I have had hyper POTS for 30 years (my entire adult life). Last year I had two heart attacks that were caused as prinzmetal angina. Which simply is endothelial cell function to the point that my coronary arteries completely close off. I have attacks without MIs often. Nothing helps but an IV at the ER of Trandate (part alpha blocker and part beta blocker). I am already on .5 mg of clonidine (yes, a massive overdose) and maxed out beta blocker PLUS saline IVs twice a week.

Not to scare people, but this is what can happen. Now - anybody with any ideas of how I can reduce these events? And how I can get my primary care to believe it can happen again and is happening at home? Of course, this never happens on a doctor appointment.

Went to the ER on Tuesday with very high BP, prinzmetal angina and SOB. Cardiologist said "we need to restrict your fluid" - !!! I pointed out that I had a PORT where I got saline twice a week which had reduced the events significantly. He then told me I was imagining the SOB and my BP was 190/100 lying down and that was acceptable to him! Then he sent me home.

Any ideas how to handle the illness AND the ER? Thanks for this thread.

[Elegiamore]

How ridiculous - also on Trandate oral maxed out daily. Again, any ideas/suggestions? TY

[juliegee]

Ele-

Sounds so much like Kounis Syndrome http://en.wikipedia.org/wiki/Kounis_syndrome This occurs when your arteries spasm shut & actually cause MI's in the absence of actual blockages.

Folks with mast cell disease (which causes hyperpots) can get this with no apparent trigger. Do you have any "allergy" type symptoms?

Julie

[juliegee]

Ele

...a few more thoughts. Kounis syndrome may also explain why saline IV's are so helpful. if you have some sort of chronic "allergic" condition, your degranulating mast cells could be causing a vasodialation of your vasculature leading to a plasma dump.

Looks like Kounis is treated dually- both as though the patient is having a cardiac event AND an allergic reaction (H-1s, H-2's, epi, and IV fluids)

http://intranet.santa.lt/thesaurus/REZIDENTUI/KORONARAI/Treatment%20of%20Kounis%20syndrome.pdf

[anna]

Wow Elegiamore, that is so scary, actually I am not sure which is more frighting for you the actual medical event or the way you have been brushed off by the ER Dr.

I had many Angina type episodes (nothing as horrid as yours) my then GP thought I was nuts!! but as my BP was so high he tried me on a calcium channel blocker Amlodipine Vasospastic angina Amlodipine has been demonstrated to block constriction and restore blood flow in coronary arteries and arterioles in response to calcium, potassium epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro. This inhibition of coronary spasm is responsible for the effectiveness of amlodipine in vasospastic (Prinzmetal's or variant) angina.(http://en.wikipedia.org/wiki/Amlodipine) It is so odd that I have not had these episodes since being on Amlodipine!!! Have you tried this med before? You would have to be careful with it I guess if you do have MAST Cell stuff going on, as it is not well tolerated by some people.

[RichGotsPots]

how bad is your SOB? Did you get an Echo of the lung?

[E246]

Hi,

have been following this post - lots of reading - very interesting in search for explanations.

I was told in hospital today my chest pain does not fit classic pots chest pain or microvasular chest pain as it was still present after i lay down. When it is bad and i have had surges to it doesn't get immediately better.

Any opinion - really upset by the glib arrogance.

[anna]

My chest pain and SOB was there at sitting as well but on thinking about it it was relieved some if my legs were elevated, (not just lying flat) even without Meds!!

[E246]

Anna,

The episodes always start of from exertion it's just they do not always go immediately on sitting and it they combine with adrenaline surges i feel like i have been kicked in the chest and really have to bed rest for sometime.

Have you been diagnosed with microvascular disease or it it solely as a result of the eds. or has eds caused microvascular angina.

Thanks.

i have found your post really helpful - it has given me enough to convince someone to prescribe the right medication. Are you seen only by your GP.

Thanks again

[RichGotsPots]

My chest pain and SOB was there at sitting as well but on thinking about it it was relieved some if my legs were elevated, (not just lying flat) even without Meds!!

Anna, sounds just like mine. I also get tons of relief by drinking half a gallon of water. People with connective tissue disorders (i.e EDS) also can get Pulmonary Hypertension..http://www.phassociation.org/page.aspx?pid=3145

[Serbo]

just bumping this thread as it's very informative. I can't help but think terms like microvascular angina and small vessel dysfunction are essentially the same thing at least when it comes to patients with connective discarders!

But distinct from that it seems you have kounis which only effects those of us with the mast cell component. I'm sure it must also be possible to have Kounis or at least vasospams induced by degranulation, and have variant/prinzmetal angina also.

Perhaps if you are prone to vasospasm (have variant angina anyway), kounis is secondary if you have a mast cell disorder.

I am confident that if i ate a cheese sandwich now i could induce intense left sided chest pain, but short of an ECG i guess there's no way to check if it's a kounis. I get the raised BP response in these situations but not generally above 150. I also get the adrenalin rush, but difficult to decipher if thats anxiety in response to chest pain.

[E246]

Serbo, Have you been diagnosed for Mast cell disorder?

Sometimes i feel like i am the only person on this site who has no tests done so am still not sure quite what is causing my problems or what type of issues are causing the complications in my pots. The doctor last month said - we can only treat the symptoms - the research will be done in America. I think males with these chest pain problems are less likely to be suspected of psychological problems.

Can you tell me what things you have been tested for regarding the chest pain etc. I have had the usual ecg/echo/chest xray. I was told that the chest pain was neither pots nor cardio by a very unpleasant cardio doctor who knew nothing about pots. Was also told by another pots doctor that it was normal to cope with the ups and downs of adrenaline as though i am a neurotic housewife. I explained that I run a dynamic expanding design company and am used to dealing with stress effectively. And rather than being overly focused on my health i am trying to work at a job i love and find it hard to have time to keep up with the research on this site which I think this site is brilliant and seems the only chance i have of getting any answers.

I still do not know what secondary issues may be causing my problems. Sorry -a bit of a rant but feel i am wasting time when i could be finding more tailored treatment and having less problems.

Thank

[issie]

I had an ER visit a while back and they thought I was having a heart attack. But, my thoughts were it was realated to an allergy type attack. I took lots of H1's and H2's before I went to the ER and then while there they gave me nitroglycerin and IV. They kept me over night - because all indications were a heart attack - but, there was no damage that occured to the heart. The end results is a possible Kounis Syndrome finding. It probably was related to an allergic mast cell degranulation. So, those of us with MCAD can have what appears to be a heart attack. The treatments given were the correct ones - it that's what the problem was. And it worked!