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CFS & Cardiac Issues Part 2a (current as of 04/02/05) |
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The Good News: CFIDS Prevents Us from Crossing the Event Horizon "You'll notice that the last things afflicted are the lung and the kidney because they have the RAS, and therefore you really have to cross the Event Horizon to involve those. I crossed it. One third of all cases of ICM cross it, and once you cross it, there's no turning back. You either die or get a transplant. There is no turning back." "Now, for some interesting reason, CFIDS patients do not cross the Event Horizon, at least in any significant way. We don't see them in Pulmonary Edema; we don't see them in renal failure; and, we certainly don't see them needing a transplant. Therefore there is something about this disease that keeps you from progressing across the Event Horizon, though you can get cardiac involvement in the milder sense." |
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Since no CFIDS patient that I've ever known or heard about has crossed the Event Horizon, I maintain that this means that CFIDS must prevent it from happening in the first place. I crossed the Event Horizon and spiraled down because I did not have CFIDS. You have CFIDS; therefore, you're very unlikely to cross the Event Horizon, which doesn't mean that you won't over time. Peckerman believes that a certain percentage of CFIDS patients are headed right for that. However, they may take a long, long time, or die of something else before that happens.
Almost everyone with CFIDS has Compensated Idiopathic Cardiomyopathy [based on the test results he's getting]. It's the degree of compensation that varies. Some compensate very well, others less so. How will you know if you eventually lose your ability to compensate and cross the event horizon? You'll know it because you'll lie down and you'll be short of breath. When you lie down you'll no longer be able to breathe. Rather than lying down and feeling better, you'll lie flat and get short of breath. Then you know you've crossed over.
Recovery Takes Time When I had my heart replaced, one of the first things that came back was my kidneys. My brain came back, but slowly. Even though my cardiac output was a whopping 10 liters per minute with the transplant, my brain did not come back fully for 6 to 7 months. Even then, there was continued progression for about four more months before I reached near 100% or greater. In fact, what's interesting is that I now think my brain is functioning at a much higher level than has been present since I was 20. That's interesting because age 20 is when you see 10 liters per minute output. The point is that, at some interesting level, brain functionality depends on microcirculation and when you have sufficient amounts of it, you have excellent brain function. The next thing that came back was my liver/gut; I couldn't stop eating, and my gut functioned perfectly. Then, my muscles started to come back and that took 8 months. Interestingly, my skin took a long time. So, my body resuscitated in reverse order. "It's taken me over a year to fully come back despite an almost instantaneous restoration of Q, which was my only problem in the first place." "Which speaks to something very important, and that is, fundamental therapy does not instantaneously result in improvement. As a matter of fact, anything that would improve you within a matter of minutes, hours, or days is, in fact, not therapy at all. It is palliation—symptom suppression—which in fact may not be helping you at all."
Marshall Protocol & "Q" My hat is off to Trevor Marshall for identifying that the Renin Angiotensin System (RAS) is a key element in the pathology of this disease and pointing out that it acts locally as well as systemically. I didn't know that before. But I'm concerned that an ARB (Angiotensin Receptor Blocker) is being used in CFIDS patients without an awareness of its effect on "Q." Angiotensin II has two receptors that we know of, and we only understand the first, AT1. When Angiotensin II binds to AT1, it increases the hormone Aldosterone, which in turn increases blood volume. Big issue! If you block AT1 with an ARB [like Benicar], down will go your Aldosterone, and down will go your blood volume, and you could be in a heap of trouble. ARBs that bind to AT1 will constrict blood volume. I'm also concerned that the other receptor [AT2] is being ignored. No one knows what it does. Not even Merck! I suspect that it has an immune effect. An ARB like Benicar selectively binds very tightly to AT1, resulting in a two—to three-fold increase of Angiotensin II, which then binds to the wide-open AT2 receptor. And who knows what kind of immune responses that is setting off. This is just speculation, but I am concerned. "I don't believe that you can block a regulatory pathway, especially tightly, with a rebound upregulation of Angiotensin II, two or three fold, when you leave unblocked an unexplained receptor that you have no idea what that thing is doing and then hope that down the road everything will be rosy."
Etiology (Cause) What is the etiology, the cause, of this cardiac output problem? The short version is that cardiac muscles have lost power because their mitochondria are dysfunctional. They're not functioning well because of a redox-state problem. [Redox: a reversible chemical reaction in which one reaction is an oxidation and the reverse is a reduction. Look for a future article explaining redox states.] But, what causes the redox-state problem? I don't know. I just know that, like MCS and GWS and many other illnesses, we're looking at a redox-state problem. But, there's something unique about CFIDS, because this redox problem seems centered on the heart. It's not focused on the heart, at least to the extent that we can tell, in these other disorders. But there is one big, big clue. It ties in to what we know about Idiopathic Cardiomyopathy (ICM), so we need to look at that first. It may shed some light on CFIDS-linked cardiomyopathy.
Viruses According to the textbook of medicine, the list of things associated with cardiomyopathy is as long as your arm and covers three pages. But most of the things listed are infectious diseases, and viruses are at the top of the list. ICM appears to be caused, in the minds of most physicians, by a post-viral infectious disorder that evolves following a viral infection, sometimes at a relatively young age. Doesn't that sound a little bit like CFIDS?
Heavy Metals The second thing that is mentioned, for which a great deal of evidence now exists in cardiology literature, including recent publications in the Journal of American Cardiology, is heavy metals. This is the big, big clue I referred to earlier. There's an Italian article published in one of the cardiology journals about a link between ICM and mercury. The authors looked at about 13 cases of ICM, 24 cases of other types of heart disease, and 4 controls. They biopsied the heart muscle of all the participants and radiated it with neutron flux to make any heavy metals radioactive. Then they put the tissue in a chromatograph to determine with great precision exactly how many molecules of mercury were in each of the tissues. What they found was astounding. All 13 cases of ICM had 23,000 times more mercury than the controls, and 18,000 times more than the other types of heart disease. One hundred percent of the people with ICM were mercury toxic at the tissue level. Does that necessarily mean that the cause of ICM is mercury? Or, is mercury linked to some other phenomena? A professor at the University of Kentucky whom I greatly admire analyzed that data. He determined that in normal heart muscle there are not enough mercury-binding sites to have that much mercury. He said the only way you could load that much mercury into the heart muscle was if something else carried it in. There may be a cardiotropic pathogen and/or an immune-system dysregulation associated with a cardiotropic pathogen that is required to load that much mercury into the heart. [Cardio: heart; tropic: affinity for, or influencing] I doubt the cardiotropic pathogen by itself can produce ICM. I think takes a combination of a pathogen and the presence of a heavy metal like mercury.
The Nexus: Virus/Bacteria/Toxins/Allergies and Heavy Metals I believe that the proximate etiology of cardiomyopathy is a nexus between an infectious, allergic, or toxic experience, as well as heavy metals. I'll go through why I think that, but I'm not claiming I know the exact cause. I'm just claiming that, based on the medical literature on cardiomyopathy as well as what we know about CFIDS, I would lay my wagers on those two entities, and I think they both may be required, not just one. That's why I call it a nexus between the two, and you'll see why. Because the underlying issues for the etiology of a Q loss need those two entities to really get going."
Pall: Nitric Oxide + Superoxide = Peroxynitrite The pathophysiology [functional changes that accompany a disease] at the cellular level that underpins this pathophysiologic state is well elucidated by Martin Pall. [A search for "Martin Pall" on immunesupport.com will produce several articles.] One nitric oxide molecule plus one superoxide molecule equals one peroxynitrite molecule. Peroxynitrite is a reactive oxygen species, is deadly, and highly damaging. At the cellular level, it is the proximate cause of human mortality. Even if you are healthy and your body handles peroxynitrite as well as possible, you will still die of old age. "These molecules [nitric oxide and superoxide] have to be generated because they are essential for life. They are the end products of a complex scheme of oxidation reactions in the human body; necessary for, among other things, energy generation, and their production is inevitable. Indeed, if they weren't produced you would not be alive. But because they are produced, you will die of oxidation. If you live by the sword, you die by the sword. If you live by oxidation then, like any piece of iron set in an oxygen environment, you will eventually rust away, and we call that death by old age. This is called 'The Free Radical Theory of Aging.' " What do humans die of, usually? The top killer is Coronary Artery Disease [CAD], and the next is cancer. It turns out that CAD and cancer are also driven in part by peroxynitrite formation. Neurodegenerative diseases like Parkinson's and Alzheimer's are also suspected of being driven by free radical formation. Even suicide is increasingly thought to be generated by oxidative stress in the central nervous system. And, of course, MS and autoimmune diseases. And finally ICM, the path down which you seem to be going, though halted by CFS itself. But your path deviated right here, just above the Event Horizon to CFS, and you went down the CFS path for a very interesting reason. Why didn't you go down the cancer or MS or Parkinson's pathway? For some reason you started down the CFS pathway over those, and I think that's a result of preordained genetics and environmental influences that combined in a unique fashion to produce that particular road I went down—the ICM pathway. But I could not deviate [from the ICM path] because I never developed CFIDS and I went straight to a near-death experience and came back. I want to talk a little bit about these two guys [nitric oxide and superoxide], show you why they're necessary and that you have to make them, and how they can modulate your disease process. Especially how they're related to etiology. [They cause many, if not most, of our symptoms—directly or indirectly.] Nitric Oxide is made by iNOS, eNOS, and nNOS, so far identified. [The small letter in front indicates the source.] The iNOS is of particular interest because it comes from the immune system. When any kind of virus, bacteria, mold, toxin, microbe, or allergy activates your immune system, it induces iNOS, which makes copious amounts of Nitric Oxide. iNOS can make far more Nitric Oxide than eNOS and nNOS can ever make. eNOS is made by the endothelial cells in the blood vessels and is responsible for regulating microcirculation, basically. nNOS is made in neurons and is responsible for memory and learning. It is also, when highly activated, very much responsible for MCS, EMR sensitivity [electromagnetic radiation], light and noise sensitivity, and can make sleep difficult. Over-activation also amplifies pain. Your body has to make nitric oxide. If you don't make it, you have no immune system, no circulation, no brain. The question isn't do you make it; the question is do you make a lot of it. If you make a lot of it there can be repercussions downstream. What those repercussions are depends on what you're [your body is] doing with superoxide. Now superoxide is produced by the act of making energy [ATP]. It's made in the mitochondria, and for every molecule of ATP generated, you generate one molecule of superoxide—one for one. The more energy you make, the more superoxide you make. However, superoxide is generally found inside the mitochondria. Generally. Nitric oxide is found outside the mitochondria. As long as superoxide stays in the mitochondria and never leaks out, there's no way you will make peroxynitrite, because it takes one nitric oxide plus one superoxide to make one molecule of peroxynitrite.
A Little Math Now, let's stop here for a moment to talk about the coupling effect. If I have 50 molecules of nitric oxide, and five molecules of superoxide have leaked out of the mitochondria, how many peroxynitrite molecules do I generate? Five. If I make 10,000 nitric oxide molecules, and only 5 superoxide, how many peroxynitrite molecules do I generate? Again, five! Do you see what is happening? What dictates peroxynitrite is not the one with the highest amount, but rather the one with the lowest.
Super Oxide—Out of Control Therefore, the primary driving force behind peroxynitrite is in fact the production of superoxide. However, if superoxide is well controlled, peroxynitrite formation is limited. However, if superoxide is out of control, there are few limits to the formation of peroxynitrite. It's purely a function of energy production. The more energy you produce, the higher the peroxynitrite may go, especially if nitric oxide is also out of control. If everything worked as intended, the mitochondria would take in oxygen and nutrition, and output carbon dioxide, water, and ATP (energy). You have enzyme systems embedded in the mitochondria that can break superoxide down to water to prevent superoxide from leaking out of the mitochondria. One enzyme system is called Superoxide Dismutase (SOD). Actually, the enzyme breaks it down to hydrogen peroxide and then down to water, via Glutathione Peroxidase, which depends on selenium and glutathione. [Without proper amounts of selenium and glutathione, the enzyme cannot do its job.] For the enzyme [SOD] to break superoxide down properly, selenium is supposed to bind to Glutathione Peroxidase. However, if mercury is present in any amount and you have no defense against it [and there are defenses], it competes for that binding site and blocks the selenium. When mercury displaces selenium at the binding site, the function of that enzyme is knocked out. At that point, you have no way to oxidize superoxide down to water, and superoxide starts to leak out contributing to the formation of deadly peroxynitrite. How much superoxide leaks out depends on how much energy you're generating [and thus how much superoxide], as well as the presence of other defense mechanisms. CoEnzyme Q10 is one and Lipoic Acid is another. CoQ10 within the mitochondria and Lipoic Acid in the cytoplasm bind excess superoxide so it's unavailable to couple with nitric oxide to produce peroxynitrite. Taking sufficient CoQ10 under certain redox state conditions, would allow you to make more energy and not get creamed with peroxynitrite. [Redox will be discussed in another article.] But, if you keep raising CoQ10 in an inappropriate redox state you may actually generate more superoxide, and that's when the CoQ10 bites you. [Some patients who cannot tolerate CoQ10 find that its analogue, Idebenone, works better.] Glutathione production is linked to ATP production, because the more ATP (energy) you make, the more Glutathione you need to keep the enzyme breaking the resulting superoxide down to water. If you don't, then the lack of Glutathione will actually result in injury to the mitochondrial membrane and a drop in ATP. That's the Gibbs Free Energy Equation, which says that Glutathione concentration and ATP generation are intimately linked. 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.]
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