BENEFICIAL EFFECTS OF MAGNETIC FIELDS ON THE HUMAN HEART A REVIEW OF CURRENT ADVANCES AND PROPOSED MECHANISMS

The main purpose of this manuscript is to introduce the reader to the present “state of the art” in experimental Low Level Magnetic Fields nerve stimulation approaches to improve chaotic cardiac arrhythmias and muscle contractions. The area addressed in this paper is the transcutaneous application of Low Level Magnetic Fields to a branch of the vagus nerve. Cardiac Arrhythmias such as Atrial Fibrillation, as well as and muscle contractility were reversed by Low Level Transcutaneous Stimulation (LL-TS) of the Auricular Branch of the Vagus Nerve (ABVN). This treatment has been successfully reported in humans as well as in awaken and anesthetized animals such as rodents and dogs. The functional improvement has been attributed to a reversal of cardiac myocytes remodeling (reversal of fibrosis) resulting from experimentally provoking induced rapid heartbeats. The prolonged duration of a tachycardia state induces intracellular accumulation of glycogen leading into fibrosis, this in turn is hypothesized to impede the intercellular electrical communications of the specialized cardiac cells. It also reduces the functional ability of the main pumping chamber (Left Ventricle).


Introduction
The purpose of this manuscript is to propose a mechanism (based on published data) for the effect on specialized muscle cells (cardiac myocytes) by Low Level Electrical Transcutaneous Stimulation (LL-TS) of the auricular branch of the vagus nerve (ABVN). Glycogen accumulation in atrial myocytes has been hypothesized to induce fibrosis and atrial fibrillation (AF) (1,2). The LL-TS stimulation has been reported to attenuate unwanted interstitial fibrosis and collagen degradation in the atria and ventricle myocytes (3,4,5). Fibrosis has been identified as a factor for arrhythmia, which is a group of conditions where the heartbeat is irregular; it sometimes could lead into severe symptoms requiring medial care. One common arrhythmia AF and its generation have been identified to start in the upper chambers of the heart (atria). Its triggers are multifactorial, such as coronary artery disease and hypertension amongst others; and it may "also occur in the normal heart, a condition known as lone AF" (6). Over the years attempts have been made to control AF by life style modifications (7), pharmacological intervention or aggressive diseased tissue destruction (ablation). Catheter ablation is increasingly offered to patients who suffer from persistent symptoms due to AF, "this recommendation is based on a growing body of evidence illustrating its efficacy compared with antiarrhythmic drug therapy" (8). Atrial remodeling is defined as any change in atrial structure or function that promotes atrial arrhythmias. In the ventricles, remodeling is defined as any change in structure that decreases muscle performance. Preliminary results of LL-TS of the ABVN are encouraging in the atria and left ventricle. The mechanism causing this improvement is unknown at present.

Materials and Methods:
A literature search was conducted leading to the contents of this manuscript.

LL-TS in the Atria (Upper Chambers)
LL-TS can reverse rapid atrial pacing-induced atrial remodeling and inhibit AF inducibility, suggesting a potential noninvasive treatment of AF.

LL-TS on the Left Ventricle (Main Pumping Chamber)
Low Level Transcutaneous Stimulation (LLTS) of the auricular branch of the vagus nerve "significantly reduced LV end systolic and end diastolic dimensions. Improved ejection fraction (contractility)", and also "attenuated interstitial fibrosis and collagen degradation in the noninfarcted myocardium when compared with the control group". In both instances, in the atria or left ventricle, LL-TS has contributed to a reversal of the unwanted remodeling.

Glycogen and AF
The literature search also yielded some interesting findings. We know that by definition myocytes remodeling entails an accumulation of interstitial fibrosis, linked to intramyocyte glycogen accumulation. Also Intracellular glycogen increase in cardiac muscles cells has been hypothesized to be related to the brain Hypothalamic-Pituitary-Adrenal axis (HPA) response to stress (9).

Acupuncture and AF
Published data also shows that "acupuncture treatment prevents arrhythmic recurrences after cardioversion in patients with persistent AF. This minimally invasive procedure is safe and well tolerated" (10,11,12,13), Integrated (serial) acupuncture treatments have resulted in AF cessation.

Acupuncture and Hypothalamus Gene Transcription
Published data also shows a direct effect of acupuncture on hypothalamic DNA methylation. DNA methylation is described as one of several epigenetic (non-genetic mechanisms that cells use to control gene expression), in other words acupuncture places some genes in the "off" position (14).

Association of gene expression with AF
Published data also shows gene expression with AF. "We examined associations of gene expression with AF in a large community-based cohort. Our study revealed several genes and signaling pathways that are potentially involved in AF-related transcriptional regulation" (15).

Interaction of Fibrinogen with a magnetic source (Protein Coagulation)
Published data also shows an interaction of fibrinogen with a low level magnetic source.
Fibrinogen is a soluble protein present in blood plasma, from which fibrin is produced by the action of the enzyme thrombin. Studies have demonstrated "that the rate of protein coagulation during the formation of fibrin gel under the action of thrombin on fibrinogen decreases ∼2 times in the presence of Low Level emissions by magnetite nanoparticles, and the magnitude of the average fiber mass/length ratio grows" (16).

Brain Cortex Glucose Metabolic Changes are associated with HPA Axis Response to Stressor
This most interesting published data links Brain Cortex changes in glucose metabolism with HPA axis response to external stressors, "single electrical stimuli applied to the digital nerves can reduce for a short period the excitability of motor cortex to magnetic stimulation. This occurs at a time when the same stimulus is evoking an excitatory (E2) reflex in the average surface-rectified EMG" (18).

Low Level Magnetic Fields and Fibrin Inhibition
This published data introduces a microscopic tabletop technique that demonstrates endogenous Low Level Magnetic Fields (LLMFs) biomagnetic tissue crosstalk between human hair and blood. This interaction induces red blood cells (RBCs) agglutination, inhibits fibrin formation ( Figure  1) and induces RBCs Rouleaux Formations (19). These findings correlate with the effect of exogenous static magnets as well as pulsating low-level magnetic fields applied to small animals showing to affect blood parameters. There were increases in blood coagulation parameters attributed to the treatments (20,21). Is also in support of the effect of LL-TS of the ABNV.

Discussion
This author is aware of the complex interactions between the nervous system and circulatory. The heart being at the center with its blood pumping action and electrical activity; and the brain with its complex signals affecting organ functions. The data presented only scratch the surface of the endogenous molecular, and biomagnetic tissue cross-talk of the human body; nevertheless some conclusions could be inferred by the published findings by this author and others. For example: 1) The literature search also yielded some interesting findings. We know that by definition myocytes remodeling entails an accumulation of interstitial fibrosis, linked to intramyocyte glycogen accumulation. Also Intracellular glycogen increase in cardiac muscles cells has been hypothesized to be related to the brain Hypothalamic-Pituitary-Adrenal Axis (HPA) response to stress (9). remodeling (reversal of fibrosis) mimics the fibrin inhibition by LLMFs of the hair shaft. This is shown in Figure 1 and other supporting figures are published in (19). 4) The issue of a stimuli to the ear (Auricular Nerve) reversing the cardiac myocytes remodeling, could be explained by a similar approach where the acupuncture like stimulation of the cardiac-related neurons in the auricular point brain medulla evokes cardiovascular inhibition (10). Does a LL-TS nerve stimulation the brain cardiac neurons have the same effect as if applied directly to the cardiac myocytes? The data seems to support the question. 5) The published data also shows a beneficial effect of acupuncture to cardiac myocytes remodeling. The acupuncture data is somewhat isolated to selective patients undergoing arrhythmia conversions via electrical shocks. At present, the data is not reliable enough to be considered as a proposed mechanism for myocytes fibrin inhibition.

Summary
The printed body of knowledge search in the area of the effect of glycogen, fibrosis and LL-TS on cardiac arrhythmias yielded the references cited in this manuscript.
It can be stated that the success of LL-TS of the ABVN on reversing atrial and ventricular myocytes remodeling is caused by an inhibition in fibrin formation. That the underlaying common denominator mechanism of the inhibition appears to involve protein coagulation.