UMLS:C0151744 - FACTA Search

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Query: UMLS:C0151744 (myocardial ischemia)
31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of sudden-death ischemic heart disease (SDIHD) remains an enigma. Data will be presented which suggest that SDIHD may be due to hypomagnesemia in and around the coronary arterial and arteriolar vessels. We have found that blood vessels (especially arteries and arterioles) deficient with respect to Mg can undergo constriction and spasm; the greater the reduction in Mg2+, the greater the magnitude of the spontaneous contractile responses. The higher the Ca2+:Mg2+ ratio, the greater are the magnitudes of these contractile responses. A severe deficit in surface membrane Mg2+, in particular, results in intense vasospasm. Using direct in situ high resolution microscopy (3000 x), we have found that a lowering of Mg2+ around perfused arterioles (15--20 microns i.d.) will also result in spontaneous vasoconstriction and, in addition, increased arteriolar resistance, tissue ischemia and reduced venous outflow. We have also found that the constrictor actions of certain circulating vasoconstrictor hormones (i.e., angiotensin, serotonin, acetylcholine) are enhanced when [Mg2+] is lowered below the levels normally found in plasma. Other direct studies, from our laboratory, indicate that [Mg2+]o regulates calcium exchange and content of vascular smooth muscle. In summary, the concept to be presented suggests that a deficiency in dietary Mg2+ is a key factor in the high incidence of mortality noted in SDIHD in nations of the Western world. The hypomagnesemia produces progressive vasoconstriction, vasospasm and ischemia, which, given time, will lead to SDIHD.
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PMID:Sudden-death ischemic heart disease and dietary magnesium intake: is the target site coronary vascular smooth muscle? 39 Mar 30

Ca2+ ions are often invoked as potential initiators of cardiac arrhythmias in pathophysiological situations which are associated with an increase of free [Ca2+]i. It is well documented that elevated [Ca2+]i may produce SR release of Ca2+ and oscillations of membrane potential, thereby leading to triggered or spontaneous ectopic activity. The relation among elevated free [Ca2+]i, electrical cell-to-cell coupling, conduction slowing, and reentrant arrhythmias is more speculative. If Ca2+ (e.g. in mechanically injured cells) has direct access to the cellular interconnections (gap junctions), rapid uncoupling occurs at [Ca2+]i which is even within the range of a normal contractile cycle. If cellular integrity is preserved and changes of [Ca2+]i are imposed by extracellular interventions, the effect of [Ca2+]i is critically dependent on pHi. At normal pHi, transcellular conductance remains normal even if [Ca2+]i is increased to bring the cells into a hypercontractile state (> 1-2 microM). At decreased pHi, rapid uncoupling develops at low [Ca2+]i. Comparison of the conduction delay between two cells (or conduction velocity in a simulated conducting medium) with the [Ca2+]i-mediated increase in coupling resistance suggests that the transition from normal conduction velocity to conduction block (a key event in re-entrant arrhythmias) occurs within a relatively narrow range of [Ca2+]i or pHi, almost like a threshold phenomenon. Major efforts have been made in recent years to assess the changes of electrical cell-to-cell coupling and [Ca2+]i in myocardial ischemia. Therefore, the discussion of the role of [Ca2+]i as a modulator of electrical coupling is made in this pathophysiological setting. Comparison of several studies indicate that cell-to-cell resistance and [Ca2+]i in ischemia increase at the same time (10-15 min after perfusional arrest). Since other potential uncoupling processes (delta ATP, delta Mg2+, amphiphilic metabolites, delta pHi) show a similar time-course, it is difficult to attribute cell-to-cell uncoupling in ischemia solely to an increase in [Ca2+]i. Both an initial decrease of membrane excitability and subsequent electrical cell-to-cell uncoupling characterize the early phase of ischemia. The first mechanism is assumed to be more important for the generation of conduction block and re-entry. However, Ca(2+)-induced cell-to-cell uncoupling may partially contribute to the second phase of the early ischemic arrhythmias and mark the transition from reversible to irreversible ischemic damage.
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PMID:The potential role of Ca2+ for electrical cell-to-cell uncoupling and conduction block in myocardial tissue. 129 7

1. In isolated aortae of the male rat [Mg2+]o withdrawal and concomitant reduction in [Na+]o (to 84 mM) induced significant increases of basal tone, but, surprisingly, this did not occur in intact aortae removed from female rats. Such tension development, however, was observed in endothelium-denuded aortic preparations from both sexes. These observed gender-related differences were not dependent on animal strain or types of tissue preparations. 2. No tension development was observed in aortae obtained from castrated males treated with oestradiol. Aortic tissues of sexually-immature male and female rats exhibited marked tension development when exposed to 0 mM [Mg2+]o and low [Na+]o. 3. Tension development in Mg(2+)-free, low-Na+ media was not tachyphylactic and completely dependent on extracellular Ca2+; addition of 1.2 mM Mg2+ to the Mg2+ and Na(+)-deficient incubation media relaxed the increase in tension to a normal basal level. 4. Two known endothelial-derived relaxant factor (EDRF) inhibitors, methylene blue and haemoglobin, induced tension development in female aortae with intact endothelium exposed to Mg(2+)-Na+ deficient media, while use of a specific inhibitor of EDRF-derived nitric oxide, viz., NG-monomethyl-L-arginine (L-NMMA), resulted in potentiation of tension development in male, but not in female, aortae. This effect of L-NMMA was antagonized by L-arginine. 5. The Ca ionophore, A23187, partially relaxed contractile responses in male aortae (with intact endothelium) which were followed by potentiated contractions. Endothelium-dependent vasodilator responses to A23187 (10(-10)-10(-6) M) of aortic rings from male or female rats in normal Krebs-Ringer bicarbonate solution were not different.6. These results suggest that: (a) as in vascular smooth muscle cells, Mg2+ plays an important role in Ca2 + homeostasis in endothelial cells, probably via Na+-Ca2+ exchange; and (b) sex steroid hormones, probably the female sex hormone, 17-beta-oestradiol, may regulate contractile responses of intact vascular smooth muscle by modifying endothelium functions through such Mg2 '-regulated internal Natdependent Ca2+ entry. These data may help to explain why female subjects, despite Mg deficiency, unlike male subjects, are protected against ischaemic heart disease and cerebrovascular disease until menopause.
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PMID:Endothelial-dependent sexual dimorphism in vascular smooth muscle: role of Mg2+ and Na+. 134 43

Chromatography of 105,000 x g supernatants of human and rat platelets on DEAE-cellulose yielded identical elution profiles containing 2 protein fractions (peaks I and II). Only peak II was found to possess guanylate cyclase activity. In the spectrum of the 105,000 x g supernatant of human platelets the absorption maximum was specified at 410 nm (the Soret band) which disappeared from the spectrum of the active protein fraction (peak II) but was detected in the nonactive fraction (peak I). The enzyme preparation was obtained in the heme-deficient form. In the experiments with rat platelets, the Soret band was absent from the corresponding spectra and the enzyme was not activated by sodium nitroprusside; i.e., in soluble guanylate cyclase of rat platelets, unlike the generally accepted notion, the heme is not a prosthetic group of the enzyme. It was shown that carnosine (beta-alanyl-L-histidine), a water-soluble antioxidant, inhibits guanylate cyclase activation by sodium nitroprusside. This inhibitory effect is caused by the interaction of carnosine with the guanylate cyclase heme and can be used for evaluating the degree of saturation of the enzyme with the heme. ADP-induced aggregation of human platelets (donors) is accompanied by a fall in the basal guanylate cyclase activity (with Mg2+) and the enhancement of the enzyme stimulation with sodium nitroprusside, protoporphyrin IX, arachidonic acid and L-arginine with simultaneous cGMP elevation in platelets. A hypothetic scheme of the regulatory role of cGMP in platelet aggregation is proposed. In the experiments with the acute myocardial ischemia of rats, 15 min after the surgery a sharp fall in the platelet guanylate cyclase activity accompanied by a decrease in the enzyme activity in the ischemic zone of the left ventricle of heart took place. The results provided evidence of the high sensitivity of platelet guanylate cyclase to pathological changes occurring in the myocardium at the earliest stages of the development of pathology.
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PMID:Soluble guanylate cyclase of platelets: function and regulation in normal and pathological states. 135 37

The activity of soluble guanylate cyclase (GC) and its regulation in the platelets and heart of normal rats and rats with experimental acute myocardial ischemia provoked by coronary ligation was examined. There was a synchronous reduction in platelet and heart GC activity immediately following 15 minutes after surgery along with a drastically marked drop in genuine baseline activity (with Mg2+) to 19 and 40% in the platelets and heart (both ischemic and intact areas), respectively. Following 24 hours, GC activity insignificantly rose (up to 35.5%) in the platelets with Mg2+, that with Mn2+ remained unchanged; in the ischemic area it decreased much more (to 30%), whereas in the intact area it partially restored (up to 70%). The stimulating effect of DTT on platelet GC activity 15 minutes after the surgery drastically rose (from 2.8 to 8), then returning to normal 24 hours later. The findings show an enhancement in free radical processes typical of ischemia and indicate their high response of platelet GC at the earliest stages. Sodium nitroprusside-induced activation of myocardial GC diminished in the ischemic area in 15 minutes and virtually lacked in 24 hours. There was a less pronounced decrease in GC activation in the intact area. It is suggested that lower enzymatic activatibility is associated with heme loss. The absence of sodium nitroprusside-induced stimulation of platelet GC both in health and in the abnormality under question may be due to primary heme enzymatic deficiency.
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PMID:[Soluble guanyl cyclase of blood platelets and heart of rats with experimental myocardial ischemia]. 135 20

Passive intracoronary perfusion of therapeutic agents has been used in the clinical setting to attenuate the effects of brief episodes of myocardial ischemia. The objective of this study was to assess the effects of low-flow coronary infusion with or without Mg2+ on tissue necrosis and cardiac hemodynamics after prolonged regional ischemia. In 33 anesthetized dogs (5 excluded during study), the left anterior descending coronary artery was occluded for 6 h. Dogs were assigned to three groups: the first group (n = 8) was subjected to 6 h coronary occlusion without low-flow perfusion (controls), the second group (n = 10) received a low-flow coronary infusion of Ringer's lactate (Mg(2+)-free), and the third group (n = 10) received a low-flow coronary infusion of Ringer's lactate plus Mg2+ sulfate (15 mM). Tissue necrosis was evaluated using tetrazolium staining and was normalized to the principal baseline predictors of infarct size including anatomic risk zone (microsphere autoradiography) and coronary collateral flow. In control hearts, infarct size comprised 51.1 +/- 4.1% of the risk zone (40.8 +/- 5.1% left ventricular cross-sectional area (LV)). In the Mg(2+)-free and Mg2+ groups, risk zone size was 17.3 +/- 2.2 and 16.8 +/- 1.8% LV (p < 0.05 vs. controls), while infarct size was 23.1 +/- 3.1 and 24.9 +/- 8.1% (p < 0.05 vs. controls), respectively. Coronary collateral flow in the endocardium was similar for all of the experimental groups; however, hearts subjected to ischemia with low-flow perfusion of Ringer's lactate demonstrated significantly higher epicardial coronary collateral flow levels compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of low-flow infusion and magnesium on tissue necrosis during regional ischemia in the canine myocardium. 145 Oct 22

ATP-dependent, inorganic phosphate-supported 45Ca2+ uptake by digitonin-lysed adult rat ventricular cardiomyocytes was used to evaluate the effects of simulated ischemia and reperfusion on the physically intact sarcoplasmic reticulum. Mitochondrial reactions were inhibited with rotenone and oligomycin. 45Ca2+ accumulation in the presence of the calcium efflux inhibitors, procaine (10 mM) and ruthenium red (30 microM), was used to characterize unidirectional uptake kinetics. A decrease in pH from 7.2 to 6.6 increased the [Ca2+] K0.5 from 0.5 to 2.0 microM and reduced the apparent Vmax by 28%. In the absence of procaine and ruthenium red, at a free [Mg2+] of 0.5 mM, maximum net uptake occurred at pCa 6.2 when pH was 7.2 and at pCa 6.0 when pH was 6.6. At lower pCa, net Ca2+ accumulation declined. Increasing free [Mg2+] from 0.5 to 1 mM at pH 6.6 or to 2.5 mM at pH 7.2 increased net 45Ca2+ accumulation in the absence of procaine and ruthenium and shifted maximum uptake to pCa 5.6 and 6.0, respectively. Increases in cytosolic free [Mg2+] thought to occur during myocardial ischemia are therefore capable of inhibiting calcium efflux from the sarcoplasmic reticulum. Reducing [ATP] from 10 to 1 mM reduced maximum net 45Ca2+ uptake by 30% both in the presence and absence of efflux inhibitors. Preincubation of intact myocytes under conditions designed to simulate ischemia and reperfusion decreased 45Ca2+ uptake greater than or equal to 50%. The data indicate that myocardial ischemia and reperfusion can alter both Ca2+ accumulation and calcium release by the sarcoplasmic reticulum.
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PMID:Effects of simulated ischemia and reperfusion on the sarcoplasmic reticulum of digitonin-lysed cardiomyocytes. 155 Nov 98

Previous studies on isolated blood vessels indicate that acute withdrawal of extracellular magnesium ions ([Mg2+]o) induces calcium-dependent contractile responses, including coronary blood vessels. The present study, using isolated perfused rat hearts, was designed to assess whether low [Mg2+]o could result in cardiac failure and to gain some insight into the mechanism of action. The results show that both the myocardial oxygen consumption (by 29-38%) and oxygen tension in the coronary effluent decreased (by 18-26%) as the [Mg2+]o was decreased stepwise from 1.2 to 0.6, 0.3 and 0.0 mM. Linear-regression analysis of a plot of coronary flow versus the rate of oxygen consumption shows that there is a tendency for a rightward shift of this relationship in low [Mg2+]o and a leftward shift of the curve in elevated [Mg2+]o (4.8 mM). The experiments also show that with low [Mg2+]o, coronary flow declines 20-37%, and cardiac output and stroke volume fall 24-50% accompanied by 3- to 4-fold elevations in lactate production and eventual, irreversible cardiac failure. An interesting finding, of this study, is that the alpha-adrenoceptor constrictor agonist, phenylephrine (1-5 microM), was found to have effects very similar to low [Mg2+]o. This latter finding is consonant with our hypothesis that progressive lowering of extracellular, ionized magnesium initiates progressive coronary vasoconstriction, decreased tissue oxygenation and myocardial ischemia, which given time, in situ, in the intact host can lead to cardiac failure.
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PMID:Low extracellular magnesium results in cardiac failure in isolated perfused rat hearts. 166 20

Magnesium (Mg) deficiency can contribute to cardiac dysrhythmias and may predispose to ischemic heart disease. Most diuretic agents cause loss of Mg, but serum levels may be normal despite cellular depletion. We studied the clinical characteristics of hypertensive patients treated for at least 6 months with either hydrochlorothiazide (HCTZ) or a single nondiuretic drug. To evaluate Mg status in our patients, we measured the percentage retention of a parenterally administered Mg load as an accurate indicator of functionally available total body Mg. Serum lipid, blood chemistry, and serum Mg values were obtained, and cardiac exercise testing and Holter monitoring were done. Levels of potassium were lower, but those of serum Mg were higher with HCTZ treatment despite double the Mg load retention. The Mg load retention data indicate relative Mg depletion in the HCTZ-treated group. Eighty percent of all patients studied had abnormal retention of Mg, even though their serum levels were normal. A percentage Mg load retention determination is needed to assess accurately Mg status.
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PMID:Magnesium deficiency in two hypertensive patient groups. 169 92

It has recently been suggested that intravenous infusion of magnesium may reduce mortality and the incidence of serious arrhythmias in patients with ischaemic heart disease and acute myocardial infarction. In the present double-blind, placebo-controlled study, 298 patients with suspected acute myocardial infarction were randomized to receive either intravenous magnesium chloride (80 mmol.24 h-1) or placebo. Infusions were started immediately after admission to the coronary care unit. One hundred and fifty patients received magnesium and 148 the placebo. Ischaemic heart disease was diagnosed in 244 patients. Acute myocardial infarction was observed among 83 patients in the magnesium group and 79 in the placebo group. Both treatment groups were comparable regarding sex, age, clinical status, previous cardiac disease and medication. Serum magnesium was significantly raised during magnesium infusion compared to placebo (P less than 0.01). Fatal events were only observed among patients with myocardial infarction, but neither the in-hospital mortality (magnesium: 12.1%; placebo 10.1%) nor the mortality after a follow-up period of 245 days (median observation time) was affected by magnesium substitution. Magnesium infusion was accompanied by a significantly increased incidence of atrioventricular conduction disturbances. The results suggest that patients suffering from acute ischaemic heart syndromes do not benefit from intravenous magnesium supplementation.
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PMID:Magnesium substitution in acute ischaemic heart syndromes. 178 52

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