Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of cultured piglet primary neonatal coronary arterial smooth muscle cells to concentrations of ionized Mg2+ ([Mg2+]o (i.e., 0.48, 0.3, 0.15 mM) found in blood of patients presenting with ischemic heart disease and in hypoxic neonates resulted in concentration-dependent elevation in intracellular free Ca2+ ions ([Ca2+]i; the lower the [Mg2+]o, the higher the [Ca2+]i rise. The lowest concentration of [Mg2+]o tested, i.e., 0.15 mM, resulted in a clear rounding-up (i.e., contraction) of many of the coronary smooth muscle cells; reintroduction of normal 1.2 mM [Mg2+]o failed to restore either normal [Ca2+]i or cell shape.
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PMID:Exposure of piglet coronary arterial muscle cells to low concentrations of Mg2+ found in blood of ischemic heart disease patients result in rapid elevation of cytosolic Ca2+: relevance to sudden infant death syndrome. 945 6

Magnesium is an important constituent of the intracellular space that affects a number of intracellular and whole body functions. Magnesium balance depends on intake and renal excretion, which is regulated mainly in the thick ascending limb of the loop of Henle. The complex hormonal modulation that responds to changes in plasma concentration of other ions such as calcium and potassium is lacking for magnesium. As a result, negative magnesium balance results in a prompt decrease in plasma magnesium concentration, and hypermagnesemia accompanies renal failure with magnesium accumulation. Hypomagnesemia may result from gastrointestinal losses or renal losses, the latter due to primary renal magnesium wasting or in association with sodium loss. Hypomagnesemia may arise together with and contribute to the persistence of hypokalemia and hypocalcemia. The major direct toxicity of hypomagnesemia is cardiovascular. When urgent correction of hypomagnesemia is required, as with myocardial ischemia, post cardiopulmonary bypass, and torsades de pointes, intravenous or intramuscular magnesium sulfate should be used. Oral magnesium preparations are available for chronic use.
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PMID:Hypomagnesemia: renal magnesium handling. 945 89

Magnesium (Mg) and calcium (Ca) concentrations were determined in the abdominal aorta of 28 patients who died by acute myocardial infarction (AMI), of 52 by ischemic heart disease (IHD) and of 26 subjects deceased by accidents or from causes other than atherosclerosis. Mg concentration in the fibrous and calcareous plaques, was significantly lower than in controls. The lowest Mg values were found in those who died by AMI. Calcium concentration, especially in the calcareous plaques, was enormous as against the controls. The four-seven times decreases of Mg/Ca ratio compared with the controls imply an alteration of the arterial wall cells. Magnesium deficit in the arterial wall probably plays a certain role in this process.
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PMID:Magnesium and calcium concentration in the abdominal aorta of patients deceased by ischemic heart disease. 1076 Nov 89

Adequate magnesium stores are vitally important for life. Critically ill patients will almost always have diminished levels of circulating magnesium, and this predisposes them to a variety of adverse effects, some life threatening. The causes of hypomagnesemia are many and varied, but in the critically ill, losses from the kidneys, often secondary to medications and from the gastrointestinal (GI) tract, predominate. The measurement of magnesium is not straightforward, although many clinicians are now switching to the use of ionized magnesium from ion selective electrodes. The use of supplemental magnesium in acute flares of asthma has some support in medical literature, especially for those patients with severe disease who fail traditional therapy. Magnesium holds the preeminent position in the treatment of pre-eclampsia and eclampsia in the minds of most obstetricians, who have decades of experience showing it to be both effective and safe. Magnesium is clearly useful for certain types of ventricular tachycardia, and probably assists in the treatment of several types of supraventricular tachycardia. Its role in acute myocardial ischemia is less certain, although there is no benefit once reperfusion therapy has already been carried out. Finally, the role of magnesium in the treatment of acute cerebral insults is an exciting area of active investigation with initial studies suggesting much promise.
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PMID:Hypomagnesemic disorders. 1121 27

Experimental heart failure is associated with cardiac magnesium loss, causing increased beat-to-beat variability in the action potential. Unstable repolarization contributes to sudden death, but no therapy has been shown to reduce repolarization variability safely. We sought to test whether a prolonged infusion of magnesium sulfate (MgSO(4); 40 mmol/24 hours) would normalize QT interval variability in patients with compensated heart failure. Fifteen patients (New York Heart Association class II to III; mean age 63 years) were enrolled in a placebo-controlled, double-blind study. Surface electrocardiograms were recorded and digitized at entry and at 48 and 168 hours (drug washout). Repolarization stability was assessed using an automated method measuring each QT interval in a 5-minute epoch. The QT variability index was derived as the ratio of normalized QT-to-normalized heart rate variability. Seven of 15 patients received MgSO(4). Mean heart rate and QT did not change in either group. The QT variability index was stable in the placebo group (-0.69 +/- 0.15 at entry, -0.71 +/- 0.22 at 48 hours, -0.70 +/- 0.18 at 168 hours), but decreased significantly in the treated group at 48 hours (-0.95 +/- 0.19 to -1.36 +/- 0.13, p <0.05 repeated-measures analysis of variance), returning to baseline at 168 hours (-0.84 +/- 0.18). Regression analyses showed that administration of MgSO(4) resulted in a stronger correlation between the QT and RR interval (p <0.01). Thus, MgSO(4) stabilizes cardiac repolarization in patients with compensated heart failure due to ischemic heart disease. Magnesium therapy may be useful in altering the proarrhythmic substrate in heart failure.
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PMID:Usefulness of magnesium sulfate in stabilizing cardiac repolarization in heart failure secondary to ischemic cardiomyopathy. 1147 98

A considerable number of experimental, epidemiological and clinical studies are now available which point to an important role of Mg2+ in the etiology of cardiovascular pathology. In human subjects, hypomagnesemia is often associated with an imbalance of electrolytes such as Na+, K+ and Ca2+. Abnormal dietary deficiency of Mg2+ as well as abnormalities in Mg2+ metabolism play important roles in different types of heart diseases such as ischemic heart disease, congestive heart failure, sudden cardiac death, atheroscelerosis, a number of cardiac arrhythmias and ventricular complications in diabetes mellitus. Mg2+ deficiency results in progressive vasoconstriction of the coronary vessels leading to a marked reduction in oxygen and nutrient delivery to the cardiac myocytes. Numerous experimental and clinical data have suggested that Mg2+ deficiency can induce elevation of intracellular Ca2+ concentrations, formation of oxygen radicals, proinflammatory agents and growth factors and changes in membrane perrmeability and transport processes in cardiac cells. The opposing effects of Mg2+ and Ca2+ on myocardial contractility may be due to the competition between Mg2+ and Ca2+ for the same binding sites on key myocardial contractile proteins such as troponin C, myosin and actin. Stimulants, for example, catecholamines can evoke marked Mg2+ efflux which appears to be associated with a concomitant increase in the force of contraction of the heart. It has been suggested that Mg2+ efflux may be linked to the Ca2+ signalling pathway. Depletion of Mg2+ by alcohol in cardiac cells causes an increase in intracellular Ca2+, leading to coronary artery vasospasm, arrhythmias, ischemic damage and cardiac failure. Hypomagnesemia is commonly associated with hypokalemia and occurs in patients with hypertension or myocardial infarction as well as in chronic alcoholism. The inability of the senescent myocardium to respond to ischemic stress could be due to several reasons. Mg2+ supplemented K+ cardioplegia modulates Ca2+ accumulation and is directly involved in the mechanisms leading to enhanced post ischemic functional recovery in the aged myocardium following ischemia. While many of these mechanisms remain controversial and in some cases speculative, the beneficial effects related to consequences of Mg2+ supplementation are apparent. Further research are needed for the incorporation of these findings toward the development of novel myocardial protective role of Mg2+ to reduce morbidity and mortality of patients suffering from a variety of cardiac diseases.
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PMID:Protective role of magnesium in cardiovascular diseases: a review. 1234 4

Proto-oncogene (c-fos, c-jun) and nuclear factor-kappa B (NF-kappaB) expression, as well as DNA synthesis, in aortic and cerebral vascular smooth muscle cells (VSMCs) were upregulated by a decrease in extracellular magnesium ions ([Mg2+]o). Upregulation of these transcriptional factors was inversely proportional to the [Mg2+]o and occurred over the pathophysiologic range of serum Mg2+ found in patients presenting with hypertension, ischemic heart disease, and stroke. Removal of extracellular Ca2+ ([Ca2+]o), use of nifedipine or protein kinase C (PKC) inhibitors prevented the upregulation of the proto-oncogenes and DNA synthesis in VSMCs. These data show that [Mg2+]o may be an important, heretofore, overlooked natural modulator of proto-oncogene and NF-kappaB expression in VSMCs and that Ca2+ and PKC may play critical roles in induction of c-fos and c-jun in VSMCs induced by a decrease in [Mg2+]o. These results point to a role for low serum Mg2+ in potential development of hypertension, atherogenesis, vascular disease, and stroke.
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PMID:Expression of the nuclear factor-kappaB and proto-oncogenes c-fos and c-jun are induced by low extracellular Mg2+ in aortic and cerebral vascular smooth muscle cells: possible links to hypertension, atherogenesis, and stroke. 1294 25

Until recently the physiological role of magnesium was essentially ignored. However, with the development of new technologies to measure the intracellular free concentration of magnesium ([Mg2+]i), the biologically important fraction, there has been an explosion of interest in the molecular, biochemical, physiological and pharmacological functions of magnesium. In addition improved methods for assessing magnesium status in the clinic have contributed to the further understanding of magnesium regulation in health and disease. Magnesium deficiency is now considered to contribute to many diseases and the role for magnesium as a therapeutic agent is being tested in numerous large clinical trials. This review focuses on clinical manifestations associated with magnesium deficiency and highlights the clinical significance of hypermagnesemia. Specific clinical conditions in which magnesium deficiency has been implicated to play a pathophysiological role, namely hypertension, ischemic heart disease, arrhythmias, prec-eclampsia, asthma and critical illness will be discussed and the possible therapeutic role of magnesium will be considered. Although there is still much to be learnt regarding the exact role of magnesium in clinical medicine, there are two conditions where magnesium is now considered the therapeutic agent of choice, pre-eclampsia and torsades de pointes. Future research, both at the fundamental and clinical levels, will certainly facilitate our understanding of how magnesium contributes to pathological processes and under what circumstances it should be used therapeutically.
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PMID:Magnesium in clinical medicine. 1497 44

Magnesium (Mg) plays an essential role in a wide range of fundamental cellular reactions in patients with ischemic heart disease. It has been well known that Mg plays a pivotal role in control of cardiac excitability, neuromuscular transmission, vasomotor tone, and blood pressure, among other functions. Especially, many epidemiological, experimental, and clinical studies support a pathological role for Mg in the etiology and development of major coronary risk factors as diabetes mellitus, hypertension, and hyperlipidemia as well as ischemic heart disease. Furthermore, the therapeutic value of Mg in the management of coronary risk factors and ischemic heart disease has been clarified. Dietary Mg supplementation should be considered as a preventive element in atherosclerosis and ischemic heart disease.
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PMID:Magnesium and ischemic heart disease: a review of epidemiological, experimental, and clinical evidences. 1654 43

Previous studies have shown that glycolysis can oscillate periodically, driven by feedback loops in regulation of key glycolytic enzymes by free ADP and other metabolites. Here we show both theoretically and experimentally in cardiac myocytes that when the capacity of oxidative phosphorylation and the creatine kinase system to buffer the cellular ATP/ADP ratio is suppressed, glycolysis can cause large scale periodic oscillations in cellular ATP levels (0.02-0.067 Hz), monitored from glibenclamide-sensitive changes in action potential duration or intracellular free Mg2+. Action potential duration oscillations originate primarily from glycolysis, since they 1) occur in the presence of cyanide or rotenone, 2) are suppressed by iodoacetate, 3) are accompanied by at most very small mitochondrial membrane potential oscillations, and 4) exhibit an anti-phase relationship to NADH fluorescence. By uncoupling energy supply-demand balance, glycolytic oscillations may promote injury and electrophysiological heterogeneity during acute metabolic stresses, such as acute myocardial ischemia in which both oxidative phosphorylation and creatine kinase activity are inhibited.
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PMID:Glycolytic oscillations in isolated rabbit ventricular myocytes. 1894 70


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