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)

In-vitro experiments are presented which indicate that the concentration of extracellular magnesium ions ([Mg2+]o) can exert profound influences on the contractility and reactivity of arteries, arterioles and veins from a number of regional vasculatures in several mammalian species, including man. Hypomagnesemia can potentiate the contractile activity of a variety of neurohumoral substances and induce vasospasm. Hypermagnesemia can do the reverse, i.e., induce hyporeactivity, relaxation and vasodilatation. Data are also presented to indicate that [Mg2+]o can control the entry, distribution and exit of calcium ions (Ca2+) from vascular smooth muscle cells. Arterial and venous smooth muscles excised from rats with alloxan-diabetes mellitus or spontaneous hypertension (SHR) appear to exhibit vascular membranes which have modifications in their Mg-Ca exchange sites. Data are reviewed which suggest that certain vascular diseases (e.g., sudden-death ischemic heart disease, hypertension, eclampsia, diabetes mellitus) are associated with a Mg-deficiency. Overall, it is suggested that [Mg2+]o and membrane [Mg] may play critical roles in regulating vascular tone and homeostasis.
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PMID:Hypomagnesemia and vasoconstriction: possible relationship to etiology of sudden death ischemic heart disease and hypertensive vascular diseases. 730 71

In some smaller placebo-controlled, randomized studies, and in one larger such study (LIMIT-2, 2,136 patients), intravenous infusion of magnesium was shown to reduce early and late mortality of ischaemic heart disease in patients admitted with suspected acute myocardial infarction. In contrast, the ISIS-4 trial, which included 58,050 patients, did not show any benefit from magnesium. These discrepancies may be explained as follows; In LIMIT-2, magnesium was given early and before spontaneous or therapeutic thrombolysis (36% of the patients), in ISIS-4, however, the patients were likely to have undergone myocardial reperfusion in response to thrombolysis (70% of the patients) before receiving magnesium. Myocardial stunning may develop in association with reperfusion. Magnesium given before and during ischaemia attenuates postischaemic myocardial dysfunction. The absence of effect of magnesium in ISIS-4 is also thought to be related to the higher dose administered during the first 24 hours in this study. Early infusion of magnesium in acute myocardial infarction is a useful addition to standard therapy, and is simple, cheap and safe to administer.
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PMID:[Magnesium therapy in acute myocardial infarction. New points of view]. 765 26

The purpose of this study was to determine the effect of dietary magnesium supplementation on blood pressure and cardiovascular function of Sprague-Dawley normotensive and mineralocorticoid-salt (DOCA-salt) hypertensive rats. The rats were pair-fed for 5 wk a purified diet containing either a normal or magnesium-supplemented diet (1.5 or 10 g/kg diet). Magnesium supplementation significantly lowered blood pressure levels in hypertensive rats, but not in normotensive rats. Heart rate was not affected in either group. The blood pressure-lowering effect of magnesium supplementation in DOCA-salt hypertensive rats was associated with a lower in vivo cardiovascular reactivity to norepinephrine and angiotensin II. Norepinephrine reactivity in isolated aortae from DOCA-salt hypertensive rats was not modified by magnesium supplementation. However, endothelium-dependent relaxation to acetylcholine was improved and could be related to the release of endothelial relaxant factors. Magnesium supplementation did not affect cardiac hemodynamics in isolated heart from either normotensive or DOCA-salt hypertensive rats. Furthermore, no protective effects upon myocardial ischemia and ventricular arrhythmias were demonstrated. These findings suggest that the lowering effect of magnesium supplementation on blood pressure in hypertensive rats may be related to a vascular effect of magnesium that reduces vascular tone. Mechanisms related to the pathophysiological development of mineralocorticoid-salt hypertension may be involved.
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PMID:Dietary magnesium supplementation modifies blood pressure and cardiovascular function in mineralocorticoid-salt hypertensive rats but not in normotensive rats. 772 84

Patients with cardiac arrhythmias, ischemia, and infarction may benefit from administration of supplemental magnesium. However, the exact mechanisms for magnesium's beneficial effects remain unknown. Lysophosphatidyl choline (LPC), an amphipathic phospholipid released from cardiac cell membranes during ischemia, increases free intracellular calcium concentrations ([Ca]i) and has been implicated as a cause of cardiac arrhythmias and coronary artery spasm during myocardial ischemia. We postulated that magnesium acts by inhibiting cellular calcium overload induced by mediators such as LPC. Myocardial cells from male Sprague-Dawley rats were isolated from ventricular tissue samples and [Ca]i determined using the fluorescent dye, fura-2/acetoxymethyl ester, measured in a spectrofluorometer. The increase in [Ca]i after exposure to 100 and 200 microM LPC was recorded in cells suspended in modified Dulbecco's phosphate buffered saline solution with 0.2, 2.0, and 20 mM magnesium chloride. Differences were determined by analysis of variance with P < 0.05 considered significant. LPC significantly increased [Ca]i in the 100 microM (506 +/- 76 nM) and 200 microM (675 +/- 81 nM) concentrations, compared to baseline (301 +/- 25 nM). MgCl2 at both the 2.0 and 20 mM concentrations significantly blunted the increase in [Ca]i in myocardial cells exposed to LPC, whereas 0.2 mM MgCl2 was ineffective. LPC is a potent lipid mediator which increases myocyte [Ca]i in a concentration-dependent manner. Magnesium concentrations > or = 2.0 mM effectively antagonize the increase in [Ca]i induced by LPC. Thus, magnesium may limit intracellular calcium overload stimulated by ischemic-induced LPC release.
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PMID:Magnesium antagonizes the actions of lysophosphatidyl choline (LPC) in myocardial cells: a possible mechanism for its antiarrhythmic effects. 776 33

The second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) examined the effect of an intravenous regimen of magnesium sulphate in 2316 patients with suspected acute myocardial infarction. Treatment, according to a double-blind randomised protocol, was started with a loading injection, before any thrombolytic therapy, and continued with a maintenance infusion for a further 24 h. Cause-specific mortality of randomised patients has now been examined over 1.0-5.5 (mean 2.7) years of follow-up. Mortality rate from ischaemic heart disease was reduced by 21% (95% CI 5-35%, p = 0.01) and all-cause mortality rate reduced by 16% (2-29%, p = 0.03) in magnesium-treated patients. Magnesium protects the contractile function of the myocardium from reperfusion injury ("stunning") in experimental models; this observation accords with the 25% (7-39%, p = 0.009) reduction in early left ventricular failure in the magnesium group of LIMIT-2. For such protection to occur, magnesium must be raised by the time of reperfusion since the injury is immediate. In the clinical context the timing of magnesium treatment in relation to thrombolytic therapy or spontaneous reperfusion is likely to be critical. The early benefits of this simple and safe intervention are reflected in improved long-term survival.
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PMID:Long-term outcome after intravenous magnesium sulphate in suspected acute myocardial infarction: the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2) 791 Feb 90

Magnesium (Mg) deficiency is a common yet underdiagnosed problem in the ICU. Since only 1% of total body Mg is in the extracellular fluid, serum Mg concentrations may not adequately reflect Mg status. Utilizing techniques to measure intracellular Mg concentrations, Mg depletion has been shown to be present in about one half of all ICU patients. These patients have significantly higher morbidity and mortality rates than Mg-replete patients. Accurate identification of patients with Mg depletion requires a knowledge of the risk factors associated with Mg deficiency. These factors include poorly controlled diabetes mellitus, alcohol ingestion, severe diarrhea and steatorrhea, and the use of a number of pharmacologic agents that induce renal Mg wasting. Manifestations of Mg deficiency include hypokalemia, hypocalcemia, neuromuscular hyperexcitability, respiratory muscle weakness, and intractable arrhythmias. Mg deficiency may also play a role in the genesis of myocardial ischemia. In this article, we review the assessment, causes, and manifestations of Mg deficiency and suggest guidelines for adequate treatment.
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PMID:Should we supplement magnesium in critically ill patients? 792 43

Depending on its duration, temporary myocardial ischemia leads to a disturbance of myocardial function before irreversible cellular necrosis is developed. Mechanical, electrical, and metabolic disturbances were suggested to be possible mechanisms accounting for the altered mechanical performance in ischemic hearts. To further investigate the alteration of myocardial energy metabolism on the subcellular level, we determined, by means of nonaqueous fractionation, the cytosolic-mitochondrial distribution of high-energy phosphates and other metabolites (ATP, ADP, phosphocreatine, creatine, and inorganic phosphate) in ischemic (zero-flow) guinea pig hearts after isolated perfused working heart preparation. Additional experiments using 31P nuclear magnetic resonance spectroscopy were performed to determine pHi and [Mg2+]i changes during global ischemia. The total ATP content of myocardial tissue dropped only slowly to 76% of control ATP at 10 minutes and to 51% at 30 minutes and reached almost zero at 60 minutes of ischemia. However, striking differences were observed on the subcellular level: While cytosolic phosphocreatine was almost completely consumed after 3 minutes of ischemia (from 19.1 +/- 1.6 to 3.3 +/- 0.5 mmol/L), ATP concentration in the cytosol decreased within 30 minutes from 8.4 +/- 0.6 to only 5.4 +/- 0.9 mmol/L. Mitochondrial ATP was rapidly and linearly reduced to 60% after 5 minutes of ischemia and was nearly unmeasurable after a further 20 minutes. Thus, in contrast to the breakdown of phosphocreatine in cytosol, the only slight alteration of cytosolic ATP reveals a reduction in cytosolic ATP utilization. Moreover, the unaffected cytosolic-mitochondrial difference in the phosphorylation potential of ATP demonstrates the intact function of the ADP/ATP carrier during early ischemia. These results might indicate a disturbance of the functional coupling between carrier and phosphocreatine kinase (phosphocreatine shuttle), which could be of importance for the early contractile failure in myocardial ischemia.
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PMID:Alteration of the cytosolic-mitochondrial distribution of high-energy phosphates during global myocardial ischemia may contribute to early contractile failure. 792 21

Myocardial hypoxia and ischemia result in the production of lactate. To study the effect of lactate on the rapid Na+ current (INa), we used the whole cell voltage-clamp technique in enzymatically isolated guinea pig ventricular myocytes. Experiments were conducted at 16 degrees C. Extracellular Na+ concentration ([Na+]o) was maintained in control and test solutions and extracellular pH was 7.4. Lactate (4-10 mM, either sodium lactate or lactic acid) augmented INa in each of eight experiments, increasing the peak Na+ conductance from 75.4 to 84.7 nS (13-16% at all test voltages in the linear portion of the conductance curve). The voltage dependence of steady-state availability and the time course of inactivation remained unchanged. The increase in peak Na+ conductance was concentration dependent, with an apparent dissociation constant of 1.8 mM and Hill coefficient of 1.8. Lactate in the range of 1-10 mM did not significantly reduce the Ca2+ activity of test solutions. These effects of lactate were still observed in Mg(2+)-free test solutions and when the buffering capacity of internal solution was reinforced by increasing N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid concentration from 5 to 20 mM. In conclusion, lactate enhances INa via a mechanism that does not involve chelation of Ca2+ or Mg2+ or changes in intracellular pH. These effects of lactate on the Na+ channel might alter electrophysiological properties during myocardial ischemia and could protect the heart from ischemia-induced conduction abnormalities or, alternatively, could lead to arrhythmias.
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PMID:Lactate enhances sodium channel conductance in isolated guinea pig ventricular myocytes. 794 3

When given at physiological doses, therapy with magnesium corrects the alterations in cellular function resulting from magnesium deficiency, whereas at higher dosages, which induce hypermagnesaemic levels, magnesium possesses pharmacological effects, such as the inhibition of the calcium influx: this may alter the electrophysiological properties of heart cells, decrease catecholamine secretion, influence the synthesis of prostacyclin and/or alter platelet function. The evidence that magnesium deficiency has untoward effects in patients with ischaemic heart disease is only circumstantial and direct proof that magnesium deficiency causes cardiac disorders is at present lacking. A ubiquitous calcium-channel blockade mechanism is the main and well-established way of action whereby magnesium acts at pharmacological levels; other mechanisms may be involved as well but at present remain questionable or unsettled. On the basis of the present knowledge, beneficial effects may thus be expected from high dose intravenous magnesium therapy in the setting of acute myocardial infarction with respect to mortality rates, even when there is concurrent thrombolytic therapy, as recently demonstrated by the large LIMIT-2 study, although this could not be confirmed from the ISIS-4 trial. High dose intravenous magnesium is also a first choice therapy for terminating torsade de pointes ventricular tachycardia but cannot be considered an established therapy for other cardiac rhythm disturbances nor for settings other than acute myocardial infarction in the case of ischaemic heart disease. The preliminary evidence that magnesium deficiency has a high prevalence in patients with ischaemic heart disease and that it may have a detrimental influence on the course of ischaemic heart disease needs to be validated by larger prospective and controlled clinical studies. Magnesium therapy in ischaemic heart disease thus proves a promising approach which, however, requires that the respective pharmacological and physiological effects be distinguished and further delineated and that the type and stage of ischaemic heart disease be characterized.
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PMID:Should magnesium therapy be considered for the treatment of coronary heart disease? I. A critical appraisal of current facts and hypotheses. 799 28

The large conductance Ca2+ activated K+ channel (BK channel) has been considered to play an important role in the excitability and contractility of vascular smooth muscle cells. Activation of the BK channel causes the hyperpolarization and relaxation of vascular smooth muscle cells. It has been reported that fatty acids can affect the BK channel activity and its concentration is increased significantly during myocardial ischemia. These reports suggest that fatty acids may contribute to the ischemic coronary vasodilation by increasing the BK channel activity. However, the underlying mechanism of fatty acid-induced activation of the BK channel is still uncertain. In the present study, we measured the effect of fatty acids on the BK channel activity in rabbit coronary smooth muscle cells by using patch clamp method and also examined its underlying mechanism. Arachidonic acid (AA) dissolved in DMSO activated the BK channel in a dose-dependent manner (from 0.5 to 10 microM), and DMSO (0.1%) alone had no effect on the activity of the BK channel. Arachidonic acid activated BK channels in both cell-attached and inside-out patches, but the onset and recovery of this effect were slower in the cell-attached patch configuration. The BK channel activity was also increased by other fatty acids, including myristic acid, linoleic acid, palmitoleic acid and palmitic acid. Long chain fatty acids were more effective than short chain fatty acids (myristic acid), and there was no statistical difference between the effect of saturated (palmitic acid) and unsaturated fatty acids (palmitoleic acid) on the BK channel activity. The concentration of Ca2+ and Mg2+ in the bathing solution had no appreciable effects on the AA-induced increase of BK channel activity. From the above results, it may be concluded that fatty acids directly increase the BK channel activity and may contribute to the ischemic coronary vasodilatation in rabbit coronary smooth muscle cells.
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PMID:Fatty acids directly increase the activity of Ca(2+)-activated K+ channels in rabbit coronary smooth muscle cells. 800 92


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