Magnesium plays an important role in maintaining the normal physiological functions of the heart tissue through vasodilation by reducing vascular resistance, improving blood circulation, maintaining the electrical property of the myocardium and with the anti-inflammatory effect of Mg 2+ also shows effects similar to clopidogrel by inhibiting platelet aggregation and adhesion.
It is reported that Mg 2+ deficiency can induce oxidative stress, which in turn activates the inflammatory process mediated through nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB ). These inflammatory events trigger the transcription of various cytokines and proinflammatory mediators with increased expression of matrix metalloproteinase 2 and 9. This situation ultimately leads to various pathological conditions such as atherosclerosis, thrombus formation, and vascular calcification. Mg 2+ can also affect the ionic concentration of calcium and potassium, which has an important role in maintaining normal cardiac physiology Mg 2+ competes with calcium-binding proteins and transporters, resulting in a change in the concentration of intracellular unbound calcium.
Extracellular Mg 2+ acts as a calcium antagonist, it inhibits calcium channel conductance, increases the excitation threshold potential, and contributes to membrane stabilization Mg 2+ regulates K + , which plays a key role in myocardial conduction. Several clinical studies have revealed the relationship between low dietary magnesium intake and heart disease, and it is reported that maintaining a normal physiological level of Mg 2+ has a beneficial effect on various cardiovascular diseases In heart disease patients, magnesium supplementation reduces intimal thickness of the carotid artery (IMT), a marker of atherosclerosis associated with various cardiovascular diseases.
Coronary artery disease [CAD] and atherosclerosis
Atherosclerosis is one of the common risk factors for triggering various cardiovascular diseases. Like endothelial dysfunction and hyperlipidemia, hypomagnesemia is also considered as one of the risk factors for atherosclerosis. Mg 2+ acts as a cofactor for many enzymes such as pyrophosphatase, lipoprotein lipase, etc., which are involved in lipid metabolism. Mg 2+ deficiency can affect the function of these enzymes, resulting in altered lipid metabolism and atherosclerosis.
Thus, Mg 2+ is effective in improving the lipid profile and endothelial dysfunction. Also, Mg 2+ reduces ROS production, reduces oxidative damage and prevents blood clot formation by inhibiting platelet aggregation. These agents provide advantages in the treatment of CHD. According to a study conducted in patients with CHD, it is reported that administration of magnesium for 6 months provided improvement in maximal oxygen uptake, left ventricular ejection fraction, corrected endothelial dysfunctions and reduced platelet-mediated thrombosis in CHD patients.
Myocardial infarction
Myocardial infarction (MI) results from reduced blood flow to heart tissue due to plaque formation with interrupted oxygen supply to the myocardium.
Treatment commonly used includes nitroglycerin and aspirin. Mg 2+ provides beneficial effects through its vasodilator effects and by preventing blood clots. The anti-ischemic effect of Mg 2+ is mediated through various mechanisms, such as its calcium antagonistic property. , by maintaining energy-dependent cellular process through conserving ATP, reducing heart rate and contractility, reducing catecholamine-induced oxygen demand, and systemic afterload The Second Leicester Intravenous Magnesium Intervention Trial (LIMIT 2) reported that Mg 2+ effectively reduces mortality and left ventricular failure associated with acute MI Magnesium administration after immediate post-infarction has been reported to reduce the incidence of arrhythmia, pump dysfunction and mortality associated with acute MI.
Studies performed in various animalsmodels revealed that Mg 2+ deficiency is associated with reduced levels of endogenous antioxidants, increased levels of ROS and increased susceptibility of the cardiovascular system to oxidative stress (Dinicolantonio et al. 2018 ; Kharb and Singh 2000). ROS can attack cardiac cell membrane lipids and cytoplasmic proteins causing nuclear and mitochondrial damage. In addition, ROS can damage cell membrane polyunsaturated fatty acids (PUFA), form lipid peroxides, fatty acid radicals, and finally peroxy fatty acid radicals.
Thus, free radical initiation and propagation reactions continued to form stable products such as malondialdehyde (MDA).
which is reported to inhibit the contractile functions of the heart and thereby affect myocardial oxygen supply. PUFAs of subcellular organelles and the sarcolemma of cardiac myocytes are particularly sensitive to ROS-induced oxidative damage A study conducted in 22 patients showed that Mg 2+ deficiency can exacerbate oxidative damage in the post-ischemic myocardium, and antioxidants were found that they have beneficial effects in this condition. A study report revealed that Mg 2+ reduces infarct size and mortality rate in patients with MI A meta-analysis study shows that Mg 2+ has a beneficial effect in reducing arrhythmias in patients with MI.
Thus magnesium supplementation is considered as an adjunct in the treatment of MI Some trials fail to prove its efficacy studies of Mg 2+ input for MI.
Studies are still ongoing, due to its low cost, ease of administration, good tolerability and experimentally proven cardioprotective function.
Arrhythmia
Cardiac arrhythmia is a condition characterized by an irregular heart rate that can be either very slow (< 60 beats/min) or very fast (> 100 beats/min) and can occur at any age. The normal heart rate is maintained
from various ions such as sodium, potassium and calcium. Mg 2+ deficiency is one of the risk factors for ventricular and supraventricular arrhythmia. ECG changes seen in hypomagnesemic states include prolonged QT interval, compressed ST segment and low T wave amplitude. Hypomagnesemia results from stress or alcoholism is also responsible for causing arrhythmias Mg 2+ deficiency contributes to cardiac arrhythmia by disrupting Na + /K + ATPase activity causes an imbalance between intracellular and extracellular potassium levels, impairs the resting membrane and repolarization potential of normal cardiac electrophysiology Mg 2+ effectively prevents atrial fibrillation occurring after cardiac surgery, and intravenous magnesium is preferred as prophylaxis in this condition by the European Association for Cardiothoracic Surgery and the Canadian Cardiovascular Society In addition, in this Mg 2+ is also reported to be effective in the treatment of Torsade’s des point, digoxin-induced tachyarrhythmia, neuroleptic or tricyclic antidepressant-induced ventricular arrhythmia and Wolff-Parkinson-White syndrome. It stabilizes the cardiac membranes and is considered first-line in the treatment of Torsades de pointes. Intravenous magnesium regulates the electrophysiology of the heart by normalizing atrioventricular nodal conduction, reducing automaticity, prolonging the resistance time of the sinus node, blocking retrograde and retrograde conduction in an accessory pathway and ventricular conduction.
Hypertension and Magnesium
Hypertension is a major cause of cardiovascular morbidity and mortality. Low intake of dietary magnesium and less amounts in drinking water can cause Mg 2+ deficiency, which is considered a risk factor for the development of cardiovascular disease such as hypertension, vasospasm, atherosclerosis, etc. Also, hypertension is often associated with a low serum Mg 2+ level. Mg 2+ deficiency results in elevated vasopressin, aldosterone, and catecholamine levels, contributing to elevated BP. In addition, hypomagnesemia results in inefficient Na ion pumps. + /K + ATP driven by Mg 2+ causing dysregulation of the sodium-potassium ratio, which is elevated in hypertensive states In addition to these, arterial plaque formation, inflammation, soft tissue calcification, and arteriosclerosis also occurred in hypomagnesemia. Inflammation associated with Mg 2+ deficiency triggers ROS-mediated hypertension. Both extracellular and intracellular Mg 2+ play a key role in maintaining BP through its vasodilator property. Intracellular Mg 2+ helps reduce the level of vasoconstrictor calcium ions. Extracellular Mg 2+ acts by down-regulating endothelin 1, which facilitates vasodilation through activation of prostacyclin I 2 Magnesium’s reduction in blood pressure is proposed to be primarily mediated through its vasodilator-related reduction in peripheral vascular resistance. action .Magnesium supplements are reported to effectively counteract the increase in BP associated with various conditions such as pre-diabetes, insulin resistance and cardiovascular disease.
SOURCE: University hospital Basel, Cell 2024.
