Fibrosis, a-fib, magnesium

Hi all,

Revisiting the possibility of cardiac fibrosis in the etiology of AF is interesting, to say the least. Although out of a fib, I have always puzzled over why I was completely free of any dysrhythmias until later in life -- around age 64. I am now almost completely convinced that age + Mg deficiency conspired to remodel my atrial tissues via interstitial fibrosis, forcing muscle bundles apart and thereby changing electrical coordination of cells for the worse.

There is no doubt in my mind that Mg deficiency was part of the picture leading up to my first arrhythmias at age 64, full blown A-fib at 67, and freedom from a-fib at 74 by overcoming Mg deficiency. Here's a clue (thank you Paul and Janet Mason for your marvelous website):

[www.mgwater.com]

Possible Role of Magnesium in Disorders of the Aged




Mildred S. Seelig, M.D., M.P.H., F.A.C.N.
GOLDWATER MEMORIAL HOSPITAL, MEDICAL DEPARTMENT
NEW YORK UNIVERSITY MEDICAL CENTER
ROOSEVELT ISLAND, NEW YORK, NEW YORK 10044

Excerpt:

Collagen, Fibrosis and Aging
"Collagen becomes more abundant, as well as more rigid, with increasing age (Hall, 1969). Among the nutrients that influence the metabolism of collagen are vitamins B6 and E, which have interrelationships with Mg. Mg deficiency increases the cardiac fibrosis... "

This makes the connection: [www.ccjm.org]

'Basic Mechanisms of Atrial Fibrillation' by David R. Van Wagoner, PhD. (Cleveland Clinic)

From other sources it appears that Mg sufficiency may reverse fibrotic changes induced by Mg deficiency. Perhaps that is why over the 2 1/2 years following final freedom from the beast there has been a gradual, slow reduction of ectopic beats until now they are virtually zero.

Perhaps the complexity of age, oxidative stress, Mg deficiency, inflammation, fibrosis, a-fib is unravelling a bit.

Erling

Sounds real plausible to me, Erling.
PeggyM

Erling,

The afib/magnesium scenario you describe sounds so wonderfully straight forward, uncomplicated and plausible.

Are you really saying that fibrosis can be reversed/ cured by magnesium supplementation?

I wonder if the success of beating afib by magnesium supplementation is relative to the degree of the fibrotic change that has taken place.
I.e., it will take longer for those people with lots of fibrosis to see a change in their condition. Severe cases of fibrosis may not respond at all?


Carol A.

Erling,

How does this fit in with the pattern of nocturnal/vagally mediated afib?

Carol A.

Hi Carol,

There is information saying that just as Mg deficiency promotes fibrosis, returning Mg status to normal will promote digestion of the fibrosis, I'm guessing via activation of Mg dependent proteolytic enzymes. Now the task is to pry that information out of this computer screen. It is clear that ACE inhibitor drugs are proteolytic, and I think we should explore that. Perhaps Hans might consider this a worthwhile topic for the Conference Room? Here's a relevant article:

'Enalapril prevents perpetuation of atrial fibrillation by suppressing atrial fibrosis and over-expression of connexin43 in a canine model of atrial pacing-induced left ventricular dysfunction.'

Sakabe M, Fujiki A, Nishida K, Sugao M, Nagasawa H, Tsuneda T, Mizumaki K, Inoue H.
Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.

CONCLUSIONS: Enalapril suppressed atrial pacing-induced AF with tachycardia-mediated cardiomyopathy by suppressing interstitial fibrosis.

[www.ncbi.nlm.nih.gov]

Carol,

The idea is that regardless of how mediated or triggered, all forms of a-fib require a muscle substrate capable of fibrillation, and fibrotic infiltration in between muscle bundles will definitely do that, by messing up electrical pathways. Another article by Dr. Van Wagoner on structural and electrical remodeling of atrial muscle goes into that quite well, with wonderful color photos, even showing isolated myocytes beating:

[www.clevelandclinic.org]

Innovations: Research in Atrial Fibrillation
Cleveland Clinic Heart Center by David Van Wagoner, Ph.D.

" ... structural remodeling is frequently characterized by increased atrial fibrosis and fatty infiltration, both on the endocardial surface, and between muscle bundles."

Erling

Erling,

Is it just possible that we are looking at the light at the end of the tunnel with respect to the afib conundrum?

Rhetorical question, but, my heavens, this looks like it makes sense! I wonder if this will apply to all afib or just magnesium/fibrosis related (and therefore, no longer" lone") afib.

Carol

The problem, it seems to me, is to explain all this to your heart and persuade it to stop all that fibrillating. I think a few people have managed to do that, but i would like to see a way for Carol to do that, too.
PeggyM

The EP that did my PVI said I had lots of fibrous tissue in my heart and there is a higher probability that afib would return. It never entirely left after the ablation and pvc's are terrible and as bad or worse than before pvi. I now have a degree of afib and/or pvc's everyday. Starts in each morning after about an hour or so after arising and hits me on and off much of the day and sometimes have to sit up in a chair in order to sleep at night.
I have been taking 800 mg minimum of magnesium glycinate daily but so far I haven't been able to see any reduction of episodes; in fact they have increased. The past couple of days I have been getting a sick feeling around 10 - 11 a.m. each morning and pvc's increase. Today the sick feeling has not subsided so far and it is now 5:35 p.m.

Oh well,..................same old song again.

Glenn

Glenn, i know you told us this once before but i have forgotten, how much potassium and in what form, your doctor told you to take?
PeggyM

Peggy,
It looks like fibrosis of the heart may turn out to be a major component of afib, as Erling and others have indicated.

But, it has to be triggered by neurological imput and therefore, it is important to do mind work, like you are and I have suggested , to quiet the vagus or phrenic nerves of whatever that are over- wired to go off with some of us afibbers. I still think that the Sarno theory has a part to play.

I wonder though if the trigger of turning over on the left side in bed and just lying down can be explained by pressure on unstable, fibrotic heart tissue. This could be independent of neurological factors.

How much to attribute to the vagus nerve and how much to fibrosis of the heart is a good question.

Carol A.

Hi Glenn,

The fact that magnesium seems to be making things worse for you is a worry. Perhaps you should stop taking magnesium right away and see if that helps. As you know, recently there have been some lively discussions about that very thing (see Dean's post, Mg Toxicity, 8-17-04). Are you supplementing magnesium based on medical testing proving a deficiency? Are your kidneys in good shape? If not, it is possible that your blood level is too high. There are many web pages describing this condition and its symptoms. Excessive magnesium in the blood is a problem, as you can see in the following article on "hypermagnesemia":

[www.emedicine.com]

Author: Nona Novello, MD, Consulting Staff, Department of Emergency Medicine, Franklin Square Hospital
Coauthor(s): Howard Blumstein, MD, Assistant Program Director, Assistant Professor, Department of Emergency Medicine, Wake Forest University School of Medicine

Excerpts:

Pathophysiology: Magnesium excess affects the CNS, neuromuscular, and cardiac organ systems. It most commonly is observed in renal insufficiency and in patients receiving intravenous (IV) magnesium for treatment of a medical condition.

Causes: Most cases of hypermagnesemia are due to iatrogenic interventions and administration, especially errors in calculating appropriate infusions. Additional causes include the following: Ingestion of magnesium-containing substances such as vitamins, antacids, or cathartics by patients with chronic renal failure.

Physical: Physical findings are related to the serum magnesium levels.

Serum magnesium levels of 3.5-5.0 mEq/L are associated with the following:
- Disappearance of deep tendon reflexes
- Muscle weakness

Serum magnesium levels of 5.0-6.0 mEq/L are related to the following:
- Hypotension
- Vasodilatation

Serum magnesium levels of 8.0-10.0 mEq/L are associated with the following:
- Arrhythmia, including atrial fibrillation
- Intraventricular conduction delay

etc.

Best wishes, Glenn! Erling

Peggy,

800 mg daily magnesium glycinate
Potasium CL 20 mEq (1500 mg) 3 times daily with meals

Glenn

Erling,

Yes I had a deficiency of both mag and potassium.
My Dr. sends a sample of blood to Great Smokies Lab regularly for a 'RED CELL' check on my mag and potassium levels. He is very much aware of the necessity of maintaining proper levels.... I impressed that on him from the start after it was discovered by my cardiologist that blood levels were low.

Glenn

Carol that would go along with what happens to me when I put my left arm across to the right side of my body and also when I lay on my right side I cannot put my left arm down in front of me and I will immidiatly get a racing heart, it stops when I bring my arm back behind me.
Would the fibrosis make your heart bigger and the squeezing of it in the way I described above account for that?

Ella

Erling,

Does fibrogin develop in other parts of the body besides the heart? If it does, would those deposits be an indicator for fibrosis in the heart?

I am thinking specifically about ovarian fibroid tumors that often occur in thirty year old women. Would those tumors be an indication of low magnesium levels and an indicator of fibrogin in the heart and the development of afib?

What is the story with Enalapril? Is this something that a cardiologist would prescribe?

Carol A.

Erling - it is really great to see this fibrosis topic revisited. When I did the long Confrence Room Fibrosis examination....the main focus was that fibrosis is present in the heart and with AF....as you mention.... VonWagoner has an excellent article. You have made an important observation with the magnesium deficiency connection.

In my earlier CR post I directed readers to be sure to study the photo of a fibrotic heart...in case anyone doubted there was a connection.

I urge everyone again to go to the CR and review the post I did on Fibrosis.... let's start examining this again.... as you have brought out that magnesium deficiency and restoration of adequate magnesium could make the difference....

Here are some of the research topics I found regarding magnesium and its role in Fibrosis.....(there are many other references at the end of the CR topic)

Jackie

Magnes Res. 2002 Dec;15(3-4):307-15.

Pro-fibrogenic effects of magnesium deficiency in the cardiovascular system.

Shivakumar K.

Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695 011, India. shivak@sctimst.ker.nic.in

Magnesium deficiency is known to produce cardiovascular injury. A large body of experimental evidence supports the postulation that an immuno-inflammatory reaction and increased oxidative stress may damage the myocardium and vasculature in magnesium deficiency. Reparative/reactive fibrosis in response to the injury has, however, received little attention. Recent evidence from a rodent model of acute magnesium deficiency suggests that humoral factors may activate cardiac fibroblasts by a free radical-mediated mechanism and contribute to cardiac fibrogenesis. A similar mechanism may also promote cellular hyperplasia and increased matrix synthesis in the vasculature.


PMID: 12635886 [PubMed - indexed for MEDLINE]


Free Radic Biol Med. 2001 Oct 1;31(7):882-6.

Superoxide-mediated activation of cardiac fibroblasts by serum factors in hypomagnesemia.

Kumaran C, Shivakumar K.

Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India 695 011.

Magnesium deficiency is known to produce myocardial fibrosis in different animal models, but the underlying mechanisms are unclear. However, circulating levels of pro-oxidant and mitogenic factors are reported to be elevated in a rodent model of acute magnesium deficiency, suggesting a role for humoral factors in the pathogenesis of the cardiovascular lesions.

Probing the mechanism of cardiac fibrogenesis in magnesium deficiency, the present study furnished evidence that serum from magnesium-deficient rats has a more marked effect than serum from magnesium-sufficient rats on mitogenesis, net collagen production, and superoxide generation in cardiac fibroblasts from young adult rats.

The enhanced mitogenic response was abolished by superoxide dismutase and N-acetyl cysteine, showing that it is mediated by superoxide anion. Further, a modest inhibitory effect of the neurokinin-1 receptor antagonist, spantide, suggested that factors acting via neurokinin-1 receptors may partly modulate cardiac fibroblast function in magnesium deficiency.

The findings are consistent with the postulation that serum factors may activate cardiac fibroblasts via a superoxide-mediated mechanism and contribute to the fibrogenic response in the heart in magnesium deficiency.

PMID: 11585706 [PubMed - indexed for MEDLINE]
: Acta Astronaut. 1997 May;40(10):719-22.

Interplanetary travel and permanent injury to normal heart.

Rowe WJ.

This hypothesis is that some crewmen on prolonged space flights may develop permanent myocardial injury despite the absence of coronary atherosclerosis and even without the hazards of radiation beyond orbit. This may resuIt from atrophy of skeletal muscle and bone resulting in magnesium ion deficiency predisposing to a vicious cycle with catecholamine elevations, with the latter aggravated by stress, dehydration-provoked angiotensin elevations, unremitting endurance exercise, and in turn a second vicious cycle with severe ischemia. Toxic free radicals can develop complicating ischemia and potential high radiation, with magnesium ion deficiency and high vascular catecholamines playing contributing roles. These free radicals may lead to inactivation of endothelium-derived relaxing factor (EDRF) causing coronary endothelial injury by a third vicious cycle, increased peripheral resistance and coronary vasospasm intensifying ischemia. Local and systemic thrombogenesis could contribute ultimately to focal fibrosis of the myocardium, if the ischemia is not recognized. Sufficient magnesium and time for repair are vital.

PMID: 11543600 [PubMed - indexed for MEDLINE
1: Med Hypotheses. 2001 Jan;56(1):110-3.

Model of cardiovascular injury in magnesium deficiency.

Shivakumar K.

Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India. shivak@sctimst.ker.nic.in

Magnesium deficiency is known to produce cardiovascular lesions. It is, however, not clear as to what constitutes magnesium deficiency - reduced serum levels, reduced tissue levels or reduced intracellular levels of the ionic form of the element.

This article cites evidence in support of a hypothesis that a fall in serum magnesium levels may trigger a temporal sequence of events involving vasoconstriction, hemodynamic alterations and vascular endothelial injury to produce pro-inflammatory, pro-oxidant and pro-fibrogenic effects, resulting in initial perivascular myocardial fibrosis which, in turn, would cause myocardial damage and replacement fibrosis.

Further, angiotensin II may be the prime mover of the pathogenetic cascade in magnesium deficiency. Importantly, such a mechanism of cardiovascular injury would be independent of a reduction in myocardial or vascular tissue levels of magnesium.

PMID: 11133266 [PubMed - indexed for MEDLINE]
: Int J Biochem Cell Biol. 1997 Jan;29(1):129-34.

Magnesium deficiency-related changes in lipid peroxidation and collagen metabolism in vivo in rat heart.

Kumar BP, Shivakumar K, Kartha CC.

Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India.

Magnesium deficiency is known to produce a cardiomyopathy, characterised by myocardial necrosis and fibrosis.

As part of the ongoing investigations in this laboratory to establish the biochemical correlates of these histological changes, the present study probed the extent of lipid peroxidation and alterations in collagen metabolism in the heart in rats fed a magnesium-deficient diet for 28, 60 or 80 days.

While lipid peroxidation was measured by the thiobarbituric acid reaction, collagen turnover rates and fibroblast proliferation were assessed using [3H]-proline and [3H]-thymidine, respectively.

Tissue levels of magnesium and calcium were determined by atomic absorption spectrophotometry. A 39% increase in the cardiac tissue level of thiobarbituric acid reactive substances was observed on day 60 of deficiency (p < 0.001). A marked drop in collagen deposition rate (59%, p < 0.001%) on day 28 but a significant rise in fractional synthesis rate (12%, p < 0.001) and collagen deposition rate (24%, p < 0.001) on day 60 were observed. A fibroproliferative response in the heart was evident on day 80 but not at earlier time-points.

Thus, the present study provides evidence of increased lipid peroxidation and net deposition of collagen in the myocardium in response to dietary deficiency of magnesium. These changes were, however, not directly related to alterations in the tissue levels of Mg.

It is suggested that the increase in cardiac collagen synthesis and fibroplasia associated with Mg deficiency may represent reparative fibrogenesis, upon oxidative damage to the cardiac muscle, and is mediated by a mechanism independent of changes in cardiac tissue levels of Mg.

PMID: 9076947 [PubMed - indexed for MEDLINE]

: Magnes Res. 1993 Dec;6(4):369-78.

Magnesium and ageing. I. Experimental data: importance of oxidative damage.

Rayssiguier Y, Durlach J, Gueux E, Rock E, Mazur A.

Centre de Recherche en Nutrition Humaine, Laboratoire des Maladies Metaboliques, INRA, St-Genes-Champanelle, France.

Magnesium status may be compromised with ageing for two reasons: insufficient intake (magnesium deficiency) or alterations in magnesium metabolism (magnesium depletion). There is a large volume of literature suggesting that magnesium deficit contributes to the ageing process and to the vulnerability to age-related diseases. One of the biological changes associated with ageing is an increase in free radical formation with subsequent damage to cellular processes. Prime targets of the more reactive free radicals are unsaturated lipids in cell membranes, amino acids in proteins, and nucleotides in DNA. The accumulation of unrepaired oxidative damage products may be a major factor in cellular ageing.

Magnesium-deficient animals show an increased susceptibility to an in vivo oxidative stress and their tissues are more susceptible to in vitro peroxidation. Moreover, the protective properties of various antioxidant drugs and nutrients suggest that free radicals are involved in the injury process of magnesium deficiency. The consequences on stress susceptibility, defective membrane functions and perturbation of intracellular calcium metabolism, inflammation, cardiovascular diseases including atherosclerosis and ischaemia/reoxygenation injury, diabetes, fibrosis, immune dysfunction and other diseases associated with ageing are presented and discussed.


PMID: 8155489 [PubMed - indexed for MEDLINE]



Free Radical Biology and Medicine, Vol. 31 (7) (2001) pp. 882-886
© 2001 Elsevier Science Inc. All rights reserved.
PII: S0891-5849(01)00656-6
Original contribution

Superoxide-mediated activation of cardiac fibroblasts by serum factors in hypomagnesemia

C. Kumaran a and K. Shivakumar a * shivak@sctimst.ker.nic.in
a Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, India
Received 4 April 2001; accepted 3 July 2001


Abstract
Magnesium deficiency is known to produce myocardial fibrosis in different animal models, but the underlying mechanisms are unclear.

However, circulating levels of pro-oxidant and mitogenic factors are reported to be elevated in a rodent model of acute magnesium deficiency, suggesting a role for humoral factors in the pathogenesis of the cardiovascular lesions.

Probing the mechanism of cardiac fibrogenesis in magnesium deficiency, the present study furnished evidence that serum from magnesium-deficient rats has a more marked effect than serum from magnesium-sufficient rats on mitogenesis, net collagen production, and superoxide generation in cardiac fibroblasts from young adult rats.

The enhanced mitogenic response was abolished by superoxide dismutase and N-acetyl cysteine, showing that it is mediated by superoxide anion. Further, a modest inhibitory effect of the neurokinin-1 receptor antagonist, spantide, suggested that factors acting via neurokinin-1 receptors may partly modulate cardiac fibroblast function in magnesium deficiency.

The findings are consistent with the postulation that serum factors may activate cardiac fibroblasts via a superoxide-mediated mechanism and contribute to the fibrogenic response in the heart in magnesium deficiency.


*Address correspondence to: Dr. K. Shivakumar, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Division of Cellular and Molecular Cardiology, Thiruvananthapuram, India 695 011; Tel: +91 471-524593; Fax: +91 471-446433
[Full text] (PDF 118.1 Kb) [www1.elsevier.com]

Glenn,

Thanks -- it's good to know that your doctor is on top of this. But in my ignorance I'm wondering if it's possible to have proper red blood cell levels of Mg and yet have "hypermagnesemia" (too much magnesium in the blood). Same with potassium: does the RBC level being correct mean that there can't be "hyperkalemia"? (too much potassium in the blood). Both conditions are of course conducive to dysrhythmias, alone or together. Are you also having regular blood (serum) measurement of Mg and K?

Erling

Carol,

Although neurological triggering of a-fib is apparently quite often the case, according to many a-fibbers, it is not necessary -- it can for instance be "triggered" just by the random electrical firing of "rogue" ectopic pacemaker cells in the PVs, why PVI ablation is so successful. And a transplanted heart with all nerve connections permanently severed can still be caused to fibrillate, but only if its muscle substrate is capable of fibrillating (maybe ruled out in the selection of a candidate heart?).

For a-fib to occur, first the heart muscle has to be capable of fibrillating -- which in my case it was not for the first 64 years, regardless of stress (a lot, mental and physical), alcohol, caffeine, sugar... you name it.

But we all agree -- mind work is very important, for this and all of life's other reasons.

Erling

Erling,

Just in case you missed my earlier post, here it is again.

Thanks for your patience with all these questions.



Does fibrogin develop in other parts of the body besides the heart? If it does, would those deposits be an indicator for fibrosis in the heart?

I am thinking specifically about ovarian fibroid tumors that often occur in thirty year old women. Would those tumors be an indication of low magnesium levels and an indicator of fibrogin in the heart and the development of afib?

What is the story with Enalapril? Is this something that a cardiologist would prescribe?

Carol A.

Carol,

Fibrosis is a natural response to injury or inflammation anywhere in the body. A cut heals with a scar (fibrosis). Generalized systemic inflammation probably causes fibrosis anywhere -- but don't take my word for that (PC? Could you please get off your surfboard and help us out here?). An echocardiogram 2 1/2 years ago showed my aortic valve having "mild fibrocalcific changes" Probably any word with "fibro" indicates fibrosis. (Fibromyalgia?)

Erling


From the On-Line Medical Dictionary at [cancerweb.ncl.ac.uk] :

fibrosis: The formation of fibrous tissue, fibroid or fibrous degeneration.

fibrous tissue: Although most connective tissue has fibrillar elements, the term usually refers to tissue laid down at a wound site well vascularised at first (granulation tissue) but later avascular and dominated by collagen rich extracellular matrix, forming a scar. Excessive contraction and hyperplasia leads to formation of a keloid.

fibroid: <gynaecology, oncology, tumour> Benign smooth muscle tumours

fibrous degeneration: Not a degeneration per se, but rather a reparative process; cells and foci of tissue previously affected with degenerative processes, and necrosis, are replaced by cellular fibrous tissue.

Jackie -- Thank you! This is fabulous stuff! The good scientists certainly leave no doubt about magnesium deficiency causing fibrotic infiltration of cardiac muscle tissue. And, excellent Dr. Van Wagoner at the CCF leaves no doubt that such fibrosis makes the myocardium vulnerable to fibrillation.

Now the remaining task is to come up with those writings showing fibrosis to be reversible. Do you think that restoring magnesium status might do so by supporting production of Mg dependent endogenous fibrinolytic enzymes? My speculation is that's what happened to me, but supplemental CO-Q10 for increased cellular energy production, and omega-3 fats for cell membrane integrity, would have benefited such a process -- building enzymes requires energy, and everything depends upon the cell's membranes.

Erling

For what it's worth, here is an interesting article suggesting reversibility of liver fibrosis:

[archive.mail-list.com]

"In summary, accumulating evidence suggests that liver fibrosis is reversible and that recovery from cirrhosis may be possible. Moreover, the cell and molecular techniques to models of reversible fibrosis are helping to establish the events and processes that are critical to recovery. It is anticipated that ultimately these approaches will lead to the development of effective antifibrotics, which harness or mimic the liver's capacity for reversal of fibrosis with resolution to a normal architecture."

Erling - when I was doing the original CR report back in January '04....I became impressed with the knowledge of exercise physiologist, Dr. Wong and what he says about eliminating fibrosis from all parts of the body with the use of proteolytic enzymes as supplements because of the decline in our own ability to make sufficient enzymes... and this isn't just an aging factor...it's an over-response to trauma, as you mention, most frequently...surgery.

I'll go back into that report and find some examples.... I guess we should take this to the CR... since it is all relevant.

Jackie

Jackie,

This is so interesting. Between you and Erling, so many pieces of the puzzle seem to be falling into place.

I will try to find Dr. Wong's site and go to your posts in January, but in the meantime and before we shift over to the CR, is it your understanding that the theoretical "over-response to trauma...most frequently surgery" that results in fibrosis, a response throughout the body or to the particular part of the body, that has been traumatised through surgery? I. e., if one had back surgery, could fibrinogin turn up in the heart?

I also wonder if stress and tension (a subtle form of trauma that releases detrimental hormones) can cause fibrosis?

Can one get proteolytic enzyme supplements at a health food store?

Carol

Carol - thank Erling for revisiting this topic again.....he was the original "thinker" on this topic. The Conferrence Room topic was actually in February 04....Fibrosis occurs anywhere in the body...and not only from surgical trauma...it is the waning of natural production of enzymes that would normally take care of fibrosis...because we lack the enzymes, fibrosis builds up. It does not migrate from one place to another....if you have knee surgery, fibrosis will not appear in the heart because of that specific surgery. And yes, you can get the proteolytic enzymes Dr. Wong recommends.... iherb has them and so does Vitaminshoppe.

Also, I believe you inquired if fibrosis creates enlargement...it does not. It creates shrinking of internal organs and reduces function.

Be sure to go to the past CR proceedings and read the rest of the report and the ensuing dialog.

Here's a start on the Introduction.... What we are now looking to find is specific information about which enzyme is affected with magnesium deficiency that results in reduced proteolytic or fibrinolytic enzymes and allows fibrosis to fluorish. This will be a major find if it surfaces.

Jackie


Cardiac Fibrotic Remodeling – The Role of Fibrosis in LAF


INTRODUCTION

Atrial fibrosis – is it simply the result of AF which then causes more episodes or might it be that fibrotic remodeling as a result of aging leads to AF?

Or is the natural decline of fibrolytic enzymes at fault? Further, might we consider the oxidative stress connection? And let’s also examine the evidence suggesting the pro-fibrotic effects of magnesium deficiency.

These questions were posed to me by Erling Waller ex-afibber (75) who thinks there may be a connection. His afib began at 64 and then 10 years later, after some nutritional adjustments, his AF vanished. (See his story in Hans’ book.)

Erling has been a regular and prolific contributor of important information and was always generous with his time and support to help others seeking answers. He continues to ponder the origin of AF and finds the fibrosis remodeling connection not only intriguing but also plausible. Erling is tackling another remodeling project at the moment and asked me to present this topic to the BB.

Interrelated factors in the “Fibrotic Remodeling Theory”
I. Fibrosis mechanism
II. Mechanisms of AF
III. Inflammation and C-reactive Protein
IV. Oxidative Stress and Nitric Oxide/Peroxynitrite production
V. Magnesium deficiency

BACKGROUND

First, you must go to this site and view the color photo of a fibrotic heart and the quick time video of electrically-stimulated cardiac myocyte contracting. Keep the image of this heart in your memory as you consider fibrosis as a connection to AF.

[www.clevelandclinic.org]

This paper published by the CCF, states that atrial fibrosis is simply the result of atrial fibrillation (AF). Author and researcher David Van Wagoner, PhD, bases his conclusion on research studies. (1)


Let’s begin –

I. Fibrosis: the body’s natural scar formation or healing defense-mechanism. When functioning optimally, and in response to injury, too much repairative fibrin is always laid down and then lysed (broken down) by fibrolytic enzymes; then removed from the body via the circulatory system.

Research shows that around age 27, the body begins to build fibrotic tissue because of a decline in fibrolytic enzymes production. In atrial fibrillation, this could explain why younger people are frequently affected and also why the general age group for the onset of AF seems to be around the age of 60 years. Some individuals lack fibrolytic enzyme production ability at earlier ages than others. (Biochemical individuality.)

A logical discussion on the role of fibrosis – in terms of our causative investigation – comes from William Wong PhD, a Classical Naturopath, Exercise Physiologist, Certified Athletic Trainer (AATA), Certified Sports Medicine Trainer (ASMA) in his article, “ Fibrosis - Enemy of Life.” (2)

He says:


“In all of us as we age ( after 27), fibrosis grows inside of all of our internal organs diminishing their size and with that shrinkage comes a diminution of function. Med school anatomy teaches this lowering of function is what ultimately leads to us dying as the organs fail due to weakness.

… this leads to the question: Why does this seem to start after 27? At or around 27 our own production of proteolytic enzymes drops.

We make a finite amount of enzymes in a lifetime and use about half of that by 25. (That's the reason why young folks, though they make cancer cells from the first day of life don't usually develop that or most any of the other conditions mentioned, they have an adequate supply of proteolytic enzymes to fight off fibrosis

It is after our supply of proteolytic enzymes drops to be spread through the rest of our lifetime that we begin to develop the fibrosis conditions.

(For you docs out there it's my contention that we can measure a pre morbid state from taking measures of proteolytic enzymes just as we can predict death within 3 days by measuring the levels of Dopamine. Useful diagnostic tool maybe. Nifty research tool certainly).

So if we can deal with the laying down of fibrosis as efficiently as we did as youngsters, then we would avoid or reduce much of what is trying to shorten our lives or at least make us sick or less able.

The most important thing to put back into an aging body is are not vitamins and minerals, not herbs, not the growth hormones but enzymes, the proteolytic enzymes.

Vitamins and minerals are more properly named co enzymes and co factors in other words they are things that help enzymes to work. If the enzymes aren't there to begin with, then the vitamins and minerals have little to work on and little action.

That's the reason why vitamin / mineral supplementation works so well for some and does not do squat for others, they have little of the enzymes they need to work on.

If we put in some of the primary protein-eating enzymes, then the body will cause the "enzyme cascade" creating thousands of new enzymes from the original 4 or 5.

Regarding fibrin…. all proteolytic enzymes eat away at fibrin (fibrinolysis) to some degree but some are considerably stronger at that than others. If the proteolytic enzymes you put back are also very highly fibrinolytic then the scar tissue your body has been creating WILL be taken away.

(This is a secret that plastic surgeons, internists and pulmonologists i.e. lung doctors, are learning about systemic enzymes). The fibrin that is supposed to be there is marked by the body as an endogenous protein, in other words something that is supposed to be part of your structure, but excesses in fibrin, though deposited by the body, are marked as exogenous proteins - or as something not belonging in the body.

Remember excesses in fibrin equal:

* weak structure, (by not leaving enough space for epithelial tissue to grow through the fibrin matrix),

* restriction of range of motion ( joints and muscles)

* diminution of size and function ( internal organs).

(End of Wong quote.)

Continue at the CR site - February 04