Magnesium, enzymes: Preventing and Reversing Atrial Fibrillation.

The natural healing force within is the greatest force in getting well.
Let food be thy medicine.
Hippocrates, circa 400 BC

Preventing and Reversing Osteoporosis [1994] by Alan R. Gaby MD, MSc (biochem) provides insight into preventing and reversing atrial fibrotic remodeling, thus reversing, or avoiding, AF. In this important book Dr Gaby explains that “bone is active, living tissue, continuously remodeling itself and constantly participating in a wide range of biochemical reactions. Bone tissue consists of both cells and an intercellular matrix. Osteoblasts are the cells within bone involved in laying down new bone tissue. Osteoclasts, on the other hand, participate in breaking down of old or damaged bone (a process called resorption)”.
If osteoclasts' resorption exceeds osteoblasts' building, bone quality will lessen (osteoporosis)
[Dr. Alan R. Gaby biography, publications, more: [www.doctorgaby.com] ]

Similar to bone, cardiac intercellular matrix, comprised largely of collagen fibers, is active, living tissue, continuously remodeling itself. Fibroblasts are the cells within the intercellular matrix involved in laying down new collagen, while fibroclasts resorb collagen.
If fibroblasts' collagen deposition exceeds fibroclasts' resorption, excessive collagen (fibrosis) may result, potentiating AF.

All -blast and -clast cells perform their function via energy and magnesium dependent enzymes. Chapter 5 of Dr. Gaby’s book is titled Magnesium: The Mineral That “Does It All” and has this:
“As a cofactor in the production of ATP, the body’s basic unit of stored energy, magnesium participates in all energy dependent processes that take place in the body”.

From The Magnesium Factor (2003) by Mildred S. Seelig MD MPH and Andrea Rosanoff PhD
“Among the enzymes that have been studied intensively, over 350 need magnesium, directly, to do their jobs. . .it is indirectly required for thousands of others”.
[Drs. Seelig and Rosanoff bigraphys, more: [www.magnesiumeducation.com] ]

It has long been understood that magnesium deficiency produces cardiac fibrosis, e.g. [www.ncbi.nlm.nih.gov]
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.
Abstract
Magnesium deficiency is known to produce myocardial fibrosis in different animal models.
(continue)

An important related article by EP John Mandrola MD was presented to the forum on 4-19-'15 (thank you Jerry!):

Atrial Fibrillation Care: Put the Catheter (and Rx Pad) down [www.afibbers.org]
The last post in the thread links to four presentations at the 2011 European Society of Cardiology Congress in Paris, France. [spo.escardio.org] Together they show clearly that atrial fibrosis, defined as excessive interstitial collagen, is the prime cause of AF. The second presentation is a good summary:

Proarrhythmic potential of fibrosis

-- What do we call fibrosis?
Excessive collagen deposition.
-- The collagen network of the normal heart:
- provides support.
- maintains myocardial structure.
- sustains the transmission of force.
-- Figure 1 [depicts factors that stimulate fibroblast cells to deposit excessive collagen resulting in AF]
-- Etiology of fibrosis:
- Reactive fibrosis: Secondary to overload, stretching. (potential reversibility)
- Reparative fibrosis Induced by myocyte necrosis, apoptosis (no reversibility)
- Multiple etiologies create different substrates and produce different pictures at the myocardium, and may coexist in the same heart.
-- Permanent arrhythmia creates fibrosis by itself, as in permanent AF.

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Related science:

[www.ncbi.nlm.nih.gov]
Arkh Patol. 1975;37(3):13-9.
Fibroblast-fibroclast: The ultrastructural mechanisms of resorption of collagen fibers in involution of the connective tissue. Article in Russian
Shekhter AB, Milovanova ZP.
Abstract
Using various experimental models (postpartum involution of the uterus, resolution of a subcutaneous scar which replaced the collagen implant and connective-tissue capsule following the removal of a foreign body) and electron-microscopy and histochemical methods of investigation, intra- and extracellular resorption of the collagenous fibres was established. The main role in this process was played by fibroblasts which under these conditions could function as fibroclasts phagocyting and digesting in its cytoplasma collagenous fibrillas with the help of lysosomal enzymes. Desintegration of fibroclasts, enriching the medium with these enzymes, stimulated the extracellular lysis of the collagenous fibrillas. This lysis was particularly intensive in the presence of an inflammatory process, and even could take place before the intracellular resorption. In macrophages no intracellular lysis was observed, however, they could phagocyte denaturated collagen, deprived of structural organization.

[www.ncbi.nlm.nih.gov]
J Trauma. 1979 Oct;19(10):744-56.
Ultrastructural evidence for the presence of "fibroclasts" and "myofibroclasts" in wound healing tissues.
Baur PS Jr, Barratt GF, Brown GM, Parks DH.
Abstract
We have observed, by light and electron microscopy, fibroblast-like cells which appear to be involved in collagen fiber and filament degradation. These cells are most prominent in the dermis of mature hypertrophic scars which were clinically observed to be in the remodeling phase of wound repair. Total incorporation of collagen filaments within cellular vacuoles, as seen by TEM, appears to precede the enzymatic degradation of the collagen. Cytoplasmic contractile bundles and/or collagen filament remnants found within residual lysosomes were also seen in many of these cells. Evidence of structural reorganization within the tissue was observed by means of SEM. These cells appear to be similar to osteoclasts in function: thus we propose to name them "fibroclasts" and "myofibroclasts."

[drsvenkatesan.wordpress.com]
Expressions in Cardiology
Less Charted Areas of The Heart: The Cardiac Interstitium. Cardiac interstitial fibrosis. Amyloidosis
September 6, 2009 by Dr S Venkatesan

Human body is made up of trillions of cells. Some of these cells are specialised and connected together to form various organs.The cells that connect each other provides the structural support and maintain the organ shape and function. Traditionally these supporting cells were thought to have little functional role. Now it is well recognised these cells could be as important as the myocytes or hepatocyte. God has never created any of the human cells without any purpose. They may have important paracrine function. Healthiness of these interstitial cells are vital for the intercellular communication, cell nutrition, and it’s proper function. These cells are called by various names, the old terminology could be the connective tissue -- the tissue that connects cells. Many times fibroblasts is the common name given to all interstitial cells. Interstitium is not only filled with some bizarre mesenchymal cells, it is also a depot of sticky molecules. Now we have deeper knowledge about these, and identified various intercellular adhesion molecules, matrix metallo proteins, vitronectins, etc..

It is a great medical paradox: The specialised myocytes, hepatocytes, axonal cells are given due respect, while the role of cells and molecules that bind them together is least appreciated. In fact, in any given organ the functional cells constitute only one third of it’s weight. In the heart, myocytes form only 30% of it’s weight. It is a clear cut case of discriminating the majority !

[continue to pictures, text, website [drsvenkatesan.wordpress.com]



Edited 7 time(s). Last edit at 06/03/2015 01:10AM by Moerk.

The significance of the following is that the electrical signals emanating from the pulmonary veins are from normal cardiomyocytes that have been separated from the rest of the myocardium by pulmonary vein fibrosis.
Mørk
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Journal Immunology 2006 118, 10–24 [www.ncbi.nlm.nih.gov]

Fibrosis in heart disease: understanding the role of transforming growth factor-b1 in cardiomyopathy, valvular disease and arrhythmia
Razi Khan and Richard Sheppard. McGill University, Faculty of Medicine, Montreal, Quebec, Canada
I
Summary
The importance of fibrosis in organ pathology and dysfunction appears to be increasingly relevant to a variety of distinct diseases. In particular, a number of different cardiac pathologies seem to be caused by a common fibrotic process. Within the heart, this fibrosis is thought to be partially mediated by transforming growth factor-b1 (TGF-b1), a potent stimulator of collagen-producing cardiac fibroblasts. Previously, TGF-b1 had been implicated solely as a modulator of the myocardial remodelling seen after infarction. However, recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies are all associated with raised levels of TGF-b1. In fact, the pathogenic effects of TGF-b1 have now been suggested to play a major role in valvular disease and arrhythmia, particularly atrial fibrillation. Thus far, medical therapy targeting TGF-b1 has shown promise in a multitude of heart diseases. These therapies provide great hope, not only for treatment of symptoms but also for prevention of cardiac pathology as well. As is stated in the introduction, most reviews have focused on the effects of cytokines in remodelling after myocardial infarction. This article attempts to underline the significance of TGF-b1 not only in the post-ischaemic setting, but also in dilated and hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on atrial fibrillation). It also aims to show that TGF-b1 is an appropriate target for therapy in a variety of cardiovascular diseases.
Keywords: anti-fibrotic treatment; atrial fibrillation; remodelling; Smad; transforming growth factor-b1

[text quotes:]

Research involving atrial fibrillation has shown that myocardial fibrosis plays an important role in predisposing to arrhythmia. In fact, the arrhythmogenic activity of the pulmonary veins is partially attributed to the fact that myocardial tissue within these vessels is significantly fibrotic (Fig. 3)

Until very recently, the extracellular matrix was considered to be a static network of proteins. However, research now indicates that this network is constantly changing in both structure and composition.

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From Cardiac Dysrhythmia [en.wikipedia.org]

Automaticity

Automaticity refers to a cardiac muscle cell firing off an impulse on its own. All of the cells in the heart have the ability to initiate an action potential; however, only some of these cells are designed to routinely trigger heart beats. These cells are found in the conduction system of the heart and include the SA node, AV node, Bundle of His and Purkinje fibers. The sinoatrial node is a single specialized location in the atrium which has a higher automaticity (a faster pacemaker) than the rest of the heart and, therefore, is usually responsible for setting the heart rate and initiating each heart beat.

Any part of the heart that initiates an impulse without waiting for the sinoatrial node is called an ectopic focus and is, by definition, a pathological phenomenon. This may cause a single premature beat now and then, or, if the ectopic focus fires more often than the sinoatrial node, it can produce a sustained abnormal rhythm. Rhythms produced by an ectopic focus in the atria, or by the atrioventricular node, are the least dangerous dysrhythmias; but they can still produce a decrease in the heart's pumping efficiency, because the signal reaches the various parts of the heart muscle with different timing to usual and can be responsible for poorly coordinated contraction.
Conditions that increase automaticity include sympathetic nervous system stimulation and hypoxia. The resulting heart rhythm depends on where the first signal begins: If it is the sinoatrial node, the rhythm remains normal but rapid; if it is an ectopic focus, many types of dysrhythmia may ensue.

This [wikipedia] page was last modified on 1 June 2015, at 04:31.



Edited 2 time(s). Last edit at 06/01/2015 12:11PM by Moerk.