can idopathic postprandial syndrom lead to afib

1 ANSWERS

1. amomipais82
   

   Hi,
   Lone Atrial Fibrilation (LAF) is AF without discernible cardiovascular disease, e.g., without congestive heart failure, high blood pressure, prior cardiac surgery, rheumatic heart disease, etc. It has been associated with a number of diseases primarily involving organs other than the heart. These include seemingly widely disparate disorders such as hyperthyroidism, gastroesophageal reflux disease (GERD), dysautonomia (abnormality of autonomic nervous system), impaired glucose tolerance, etc. The term "defective substrate" has become integral to any discussion of the cause of LAF. Organ candidates for this "substrate" include at the top of the list the heart, as well as kidney, adrenal gland, gastrointestinal tract and autonomic nervous system. This defect could involve an enzyme, a hormone or receptor site, a membrane pump, channel or exchanger, to name a few. It could be environmental, genetic or both. Magnesium (Mg) deficiency has emerged as a significant player in the etiology of LAF. This is not completely unexpected, since some 350 different enzymes(1) or about 80% of all enzymatic reactions in the body(2) rely on magnesium. Although much has been written on the role of Mg deficiency in other diseases, little has been devoted to LAF.
   Mg and Cell Membranes
   
   One of the most important roles of Mg involves maintenance of the intracellular environment. It does this primarily by attaching to phospholipids in membranes (both of the cell wall and cell organelles) to reduce their permeability and enhance polarizing electrostatic effects(12). It also a required cofactor in the various membrane ATP (energy requiring) pumps. The most important of these pumps is the Na/K pump. Others include Ca/Mg, K/H and Na/H pumps. In addition there are channels (such as Ca and Na) and exchangers (such as Na-Mg, Na-Ca and Na-H). Neither channels nor exchangers require ATP and are passive (rely on diffusion). Some of these are also adversely affected by Mg deficiency. Mg is a Ca channel blocker and Mg deficiency leads to increased intracellular Ca via channel (and pump) due to a Ca gradient of 25,000:1 (outside v inside)(9). Mg deficiency also results in dysfunction of the Na-Mg exchanger(56), leading to increased intracellular Na via exchanger (and pump) due to a Na gradient of 13:1(71). If there is insufficient Mg for adequate ATP, then the primarily extracellular cations sodium (Na) and calcium (Ca) tend to leak into the cells and the primarily intracellular cations potassium (K) and Mg tend to leak out. However, membrane leakiness in magnesium deficiency depends less on ATP related activity and more on the membrane stabilizing effects of magnesium phospholipd complexes(12). This leakiness disrupts cellular function and proper gradients (difference between intracellular and extracellular concentrations). In addition Mg is an antioxidant and Mg deficiency allows accelerated free radical damage to cell membranes (lipid peroxidation), further compromising cellular cation (positive ion) homeostasis(3,24,32,60,61). Maintenance of proper cationic (Na, K, Ca, Mg) gradients is especially critical for successful muscle contraction and nerve impulse transmission. In fact the earliest symptoms of magnesium deficiency are neuromuscular symptoms, e.g., muscle twitching, difficulty sleeping, difficulty swallowing. Accordingly, the list of disorders associated with Mg deficiency is top heavy with neuromuscular diseases, e.g., asthma (bronchial smooth muscle), migraines and eclampsia (vascular smooth muscle), cramps (skeletal muscle), LAF (cardiac muscle) and even chronic constipation (GI smooth muscle).
   Mg and K
   
   Like Mg, K inhibits free radical formation(4). In fact, there are a number of parallels between these two cations. Both are inextricably linked to specific anions (Na for K and Ca for Mg). Hyperkalemia (like hypermagnesemia) does not typically occur in patients with normal renal function. Aldosterone increases the secretion/excretion of both K and Mg(5). Successfully replenishing a K deficiency (like a Mg deficiency) in the presence of low intracellular Mg is difficult and takes months(6). Even in the presence of a normal serum K, reduced dietary K can be problematic, just as for Mg(4). K and Mg both can reduce high blood pressure(7). Fruits and vegetables are great sources for both minerals (mother was right). Both because K is so vital to cardiac function and because Mg is so vital to K utilization(33), any discussion of Mg and LAF is incomplete without inclusion of K.
   Absorption and Excretion
   
   In addition to passive diffusion there appears to be an ATP requiring mechanism for Mg absorption from the GI tract(8). Similarly, in the kidney in addition to passive diffusion there appears to be an additional active transport system for the reabsorption of Mg(9,10,12,19). In short, Mg via ATP is required for a portion of its own GI absorption and renal reabsorption(19). Likewise GI absorption of K is decreased and urinary excretion increased, if there is a Mg (and therefore ATP) shortage in GI and kidney cells respectively(14,19,56). Both absorption and reabsorption of K (and Mg) worsen with age(11).
   Hormones and Mg Homeostasis
   
   Neither Mg nor K has good neurohormonal controls for either GI absorption or renal reabsorption to maintain proper balance (v parathormone, calcitonin and Vitamin D for Ca, aldosterone and atrial natriuretic peptide (ANP) for Na)(35). However, insulin, parathormone (PTH) and Vitamin D do play a role in Mg homeostasis by increasing cellular uptake(13). The former is primarily associated with carbohydrates and the latter two with Ca, a Mg antagonist. A variety of other hormones has been implicated in urinary magnesium wasting. These include catecholamines, TSH, T3, T4 (thyroxine) and calcitonin (thyroid), glucocorticoids (affect glucose metabolism, especially cortisol) and mineralicorticoids (affect sodium metabolism, especially aldosterone), glucagon (pancreas), antidiuretic hormone (ADH from pituitary) and angiotensins (liver and lungs)(14,15,20,57). Catecholamines are produced by both the adrenal medulla (humoral) and sympathetic nerves (neurotransmitter). Corticoids (corticosteroids) are produced by the adrenal cortex. High dietary sodium and calcium may also result in urinary magnesium wasting(16).
   Insulin and Mg
   
   Insulin causes cellular uptake of Mg(12). Magnesium deficiency results in insulin resistance(13) as well as impaired insulin secretion(17,22,23). Furthermore, the most significant mechanism for urinary magnesium wasting is probably through glycosuria (glucose in the urine) secondary to impaired glucose tolerance(14,21,23,25). Insulin resistance appears to be due to defective tyrosine-kinase activity (requires Mg) at the insulin receptor level and increased intracellular calcium(18). This resistance mandates release of more insulin, causing more Mg (and K) to be transported from blood into cells. Intracellular Mg (and K) must then be maintained against a greater concentration gradient (defective Ca/Mg ATPase and Na/K ATPase pumps). The concomitant urinary Mg wasting aggravates further this with additional membrane instability (decreased magnesium phospholipid complexes), causing more Mg loss and more insulin resistance (see cAMP/cGMP discussion below).
   Parathormone and Mg
   
   The parathyroid gland in response to low serum magnesium or calcium releases PTH. PTH then increases GI absorption and renal reabsorption of Mg(12). However, adequate magnesium is required for parathyroid hormone synthesis and secretion(20). So this also is a kind of a hormonal catch 22 (Mg is required for the efficacy of one of its regulating hormones) similar to the electrolyte catch 22 (Mg is required for its own cellular uptake). Mg deficiency also causes end organ PTH resistance (serum Ca does not rise when PTH is increased in Mg deficient patients)(12,48,55).
   Vit D and Mg
   
   Intestinal absorption of magnesium and calcium is enhanced by Vitamin D(52). Mg absorption in Vitamin D deficiency is decreased(72). In addition serum concentration of 1,25 dihydroxy cholecalciferol (cholecalciferol = Vitamin D3) is low or low/normal and does not rise in response to a low calcium diet. This is because the formation of 1,25 dihydroxy cholecalciferol involves a magnesium dependent hydroxylase enzyme(12). Magnesium deficiency also results in end organ resistance to vitamin D and its metabolites(12). This is another hormonal catch 22. Vitamin D increases net absorption of Mg but to a lesser degree than for Ca (34,35). The subsequently elevated blood Ca may result in greater urinary Mg wasting(12).
   Cyclic AMP/cGMP and Taurine
   
   Insulin and catecholamines function via receptors on target cell membranes, which involve cyclic AMP (cAMP). On the other hand, cholinergic receptor activity (PNS) involves cyclic GMP (cGMP). Adenylate cyclase (for cAMP production) requires Mg, whereas guanylate cyclase (for cGMP production) requires Ca(13). Consequently, in Mg deficiency the intracellular cAMP/cGMP ratio, normally between 10 and 100 to 1, is reversed(52). This partially explains the insulin receptor resistance (low cAMP) seen in impaired glucose tolerance associated with Mg deficiency. cGMP mediates the effects of ANP in target cells, i.e., enhanced natriuresis(31). This may be another reason why VMAF episodes (enhanced cholinergic receptor activity) and LAF episodes due to Mg deficiency, both associated with high cGMP, seem to revert to NSR more spontaneously. Interestingly, hyperinsulinism tends to maintain this reduction in cAMP(13). Only when intracellular GTP is raised do these neurohormones (mainly insulin and catecholamines) stimulate adenylate cyclase(13). Jean Durlach, M.D., Editor-in-Chief, Magnesium Research, President of the International Society for the Development of Research on Magnesium, and author of Magnesium in Clinical Practice, suggests that taurine may effect this turnaround (less cGMP and more cAMP). Catecholamines and insulin favor cellular influx of taurine. Taurine is a powerful membrane stabilizer. It also chelates Ca, a Mg antagonist, facilitates maintenance of intracellular K and opposes the undesirable cellular effects of insulin and catecholamines(13). Taurine plays an important role in Mg deficiency. MSG (monosodium glutamate) can lead to taurine deficiency. Taurine is made from cysteine and glutamate competes with cysteine for uptake(46).
   Autonomic Nervous System and Mg
   
   Mg is required for activity by the cholinesterase enzymes(13). One of these, acetyl cholinesterase degrades acetylcholine, the neurotransmitter substance for the PNS and for the first part of the sympathetic nervous system (SNS), specifically the nicotinic receptors of the SNS. In fact, deficiency of magnesium and excess calcium both increase the release of acetylcholine. Deficiency of either magnesium or calcium prolongs the effect of acetylcholine(58). Mg deficiency translates to enhanced vagal tone further augmented by too much or too little Ca.
   
   Catecholamine-O-methyltransferase (COMT) and monoamine oxidase (MAO) catabolize (breakdown) catecholamines. MAO catabolizes neurotransmitter catecholamines (at nerve endings), while COMT is more active in catabolizing circulating catecholamines(30). Both are part of the sympathetic nervous system (SNS). COMT requires Mg as a cofactor(28,29), i.e., low Mg translates to slightly higher sympathetic tone. These enzymatic shortfalls might produce an exaggerated response of either the PNS or the SNS at transition points, a time when many LAF episodes arise, e.g., just after ending a sprint or lying down. The neurotransmitter substance or hormone secreted on each occasion is not degraded, resulting in a prolonged overresponse. COMT also breaks down dopamine, an important hormone produced during sexual activity. Sexual activity triggers some episodes for many afibbers. The dopamine no doubt triggers automaticity in an aberrant focus with a resulting increase in PACs (see EP discussion below). The overresponding vagus causes a shortening of the AERP. Mg deficiency in this scenario (independent of K) may be the sole cause of bedtime episodes and even some more typically adrenergic episodes.
   GERD
   
   The "alkaline tide" precedes the start of any meal. This is caused by gastric cell secretion of H and Cl into the lumen for digestion of food and simultaneous extrusion of K and HCO3 into the blood. The resulting alkalosis (increased blood pH due to HCO3) causes bicarbonaturia (HCO3 in urine) to lower this pH. Unfortunately, K is lossed in the urine (kaliuria) with HCO3(54). This causes a transient drop in blood K. Furthermore, there is evidence that high vagal tone may sustain basal gastric acid hypersecretion in some persons and temporary hypersecretion during stress in others(49). Some cases of GERD (gastroesophageal reflux disease) and nonulcer dyspepsia (NUD) probably result in transient hypokalemia via the constant steady alkaline state (in plasma) that accompanies the slightly hyperacidic state (in the stomach). The K/H pump also rectifies this increase in blood pH. H goes into the blood and K comes into the cells. This requires cardiac muscle cells to maintain their intracellular K concentration against a greater gradient. Normally the concentration of K within heart muscle cells is 150 millimoles/liter (v. four mm/l outside the cell), a considerable gradient (almost 40:1) to maintain(9). Ingested protein stimulates more HCl secretion (and a stronger alkaline tide and greater kaliuria). Other suggested mechanisms for GERD related episodes of LAF include stimulation via irritation of the nearby vagus nerve during episodes of reflux. Some VMAFers (vagally mediated atrial fibrillation) associate their episodes with GERD. Curiously, many of them prefer to sleep on their right side. Vagal tone is increased when lying in the right lateral decubitus position (lying on one's right side)(67). This is because the heart is slightly higher (v. the left side position) relative to the carotid baroreceptor. This pressure receptor in the neck senses more hydrostatic pressure and signals the vagus nerve to increase tone (bad for a VMAFer). However, the preference may be because and this position promotes gastric emptying and possible relief for a GERDer.
   MSG and Aspartate
   
   Monosodium glutamate (MSG) is a common trigger of AF (and PACs) for many LAFers. NMDA (N-Methyl-D-Aspartate) receptors are located on neurons and are associated with the Ca channel(42). When glutamate or aspartate attaches to the NMDA receptor, it triggers a flow of sodium (Na) and calcium (Ca) ions into the neuron, and an outflow of potassium (K), firing the neuron. ATP pumps are required to return the ions and restore the resting state. The Ca channel is blocked by magnesium. This helps maintain membrane potentials near resting value. If the repolarized resting state cannot be maintained, e.g., hypoglycemia, defective pump (as in Mg deficiency), then the neuron fires and the channels open. This pump failure gradually allows excessive calcium/sodium build up inside the cell, which will eventually kill it(43,44). Furthermore, ATP pumps are required not only to return the ions but also to remove the glutamate. Glutamate is then converted into glutamine, another process that requires ATP. That is a total of three separate ATP and Mg requiring steps. Free radicals hinder this(45). Mg has a circadian excretory rhythm, with maximal excretion occurring at night(56). This compounds the picture for VMAFers, whose episodes are often triggered at night, since Mg deficiency is both vagotonic and glutamate potentiating. For these reasons, MSG and even mild GERD make dinner out a risky proposition for many LAFers.

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