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

Myocardial ischemia is characterized by a decrease in phosphocreatine (PCr) and Mg(2+)-ATP contents as well as an accumulation of myosin ATPase reaction products (inorganic phosphate [P(i)], protons, and Mg(2+)-ADP). The possibility that these metabolites play a role in rigor tension development was checked in rat ventricular Triton X-100-skinned fibers. Rigor tension was induced by stepwise decreasing [Mg(2+)-ATP] in the presence or in the absence of 12 mmol/L PCr. To mimic the diastolic ionic environment of the myofibrils, [free Ca2+] was set at 100 nmol/L (pCa 7); [free Mg2+], at 1 mmol/L; and ionic strength, at 160 mmol/L. In control conditions (pH 7.1, with no added P(i) or Mg(2+)-ADP), the pMg(2+)-ATP for half-maximal rigor tension (pMg(2+)-ATP50) was 5.07 +/- 0.03 in the presence of PCr. After withdrawal of PCr, the pMg2+)-ATP50 value was shifted toward higher Mg(2+)-ATP values (3.57 +/- 0.03). Addition of 20 mmol/L P(i) shifted the pMg(2+)-ATP50 to 3.71 +/- 0.04 (P < .05) in the absence of PCr and in the opposite direction to 4.98 +/- 0.02 (P < .01) in the presence of PCr. Acidic pH (6.6) strongly increased pMg(2+)-ATP50 in both the absence (3.90 +/- 0.03, P < .001) and presence (5.44 +/- 0.02, P < .001) of PCr. Conversely, Mg(2+)-ADP (250 mumol/L) decreased pMg(2+)-ATP50 to 3.26 +/- 0.06 (P < .001) in the absence of PCr; at pMg(2+)-ATP 4, no rigor tension was observed until PCr concentration was decreased to < 2 mmol/L. At acidic pH, maximal rigor tension was lower by 29% compared with control conditions, whereas in the presence of Mg(2+)-ADP, maximal rigor tension developed to 143% of the control value; P(i) had no effect. The tension-to-stiffness (measured by the quick length-change technique) ratio was lower in rigor (no PCr and pMg(2+)-ATP 6) than during Ca2+ activation in the presence of both PCr and ATP. Compared with control rigor conditions, this parameter was unchanged by Mg(2+)-ADP and decreased by acidic pH, suggesting a proton-induced decrease in the amount of force per crossbridge. In addition to their known effects on active tension, Mg(2+)-ADP and protons affect rigor tension and influence ischemic contracture development. It is concluded that ischemic contracture and increased myocardial stiffness may be mediated by a decreased PCr and local Mg(2+)-ADP accumulation. This emphasizes the importance of myofibrillar creatine kinase activity in preventing ischemic contracture.
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PMID:Myocardial ischemic contracture. Metabolites affect rigor tension development and stiffness. 815 39

Abnormal dietary deficiency in Mg as well as abnormalities in Mg metabolism appear to play important roles as risk factors for ischemic heart disease and acute myocardial infarction, namely in hypertensive vascular disease, diabetic vascular disease, insulin resistance, atherosclerosis and vasospasm. Experimental, epidemiological as well as clinical evidence that supports a role for Mg in these risk factors are reviewed. Extracellular Mg ions ([Mg2+]o) exert important actions upon divalent cation metabolism, transport and intracellular release of [Ca2+]i and intracellular free Mg ([Mg2+]i) in both vascular smooth muscle and endothelial cells. Digital imaging microscopy, using molecular fluorescent probes, clearly indicates that both intracellular free Ca2+ and intracellular free Mg2+ are compartmented in both vascular smooth muscle cells and endothelial cells. [Mg2+]o appears to exert important effects on the precise subcellular location and concentration of both [Ca2+]i and [Mg2+]i. Use of specific ion-selective electrodes for [Mg2+]o has revealed that [Mg2+]o can change more rapidly than heretofore believed in cardiovascular pathophysiologic states. The latter new findings therefore suggest that the ionized level of [Mg2+]o is an important determinant of vascular tone, contractility and reactivity.
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PMID:Magnesium, hypertensive vascular diseases, atherogenesis, subcellular compartmentation of Ca2+ and Mg2+ and vascular contractility. 826 20

The aim of this study was to investigate whether intracellular free Mg2+ (Mgr), which increases during myocardial ischemia due to hydrolysis of ATP, remained elevated during reperfusion after a relatively short period of ischemia and thereby could account for temporary post-ischemic contractile dysfunction, often referred to as stunning. 31P-magnetic resonance (31P-NMR) spectroscopy was used to follow creatine phosphate, adenosine triphosphate, intracellular inorganic phosphate, intracellular pH and Mgr simultaneously with left ventricular developed pressure (LVDP) and coronary flow in isolated rat and rabbit hearts, which were perfused (37 degrees C) according to Langndorff. LVDP was measured in an isovolumic way by means of an intraventricular latex balloon. Rat hearts (300 beats/min) were made globally ischemic for 15 min and rabbit hearts (180 beats/min) for 15 or 20 min. All hearts were reperfused for 60 min. Control hearts were perfused for 75 min without being made ischemic. During ischemia Mgr (mmol/l) increased from 0.76 +/- 0.20 to 4.34 +2- 1.99 in the rat hearts, and from 0.72 +/- 0.22 to 2.18 +/- 1.06 (15 min) and 2.35 +/- 1.26 (20 min) in the rabbit hearts. During reperfusion Mgr in the three groups returned to the level of the control hearts within 7.5 min, and LVDP within 25 min. At the end of the reperfusion period ATP content amounted to 56 +/- 17% (rat hearts), 66 +/- 10% (rabbit hearts; 15 min ischemia group) and 61 +/- 7% (rabbit hearts; 20 min ischemia group) of the pre-ischemic levels. The results confirm that in vitro stunning is a short-lived phenomenon and indicate that an increased Mgr is not involved in this temporary mechanical dysfunction.
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PMID:Post-ischemic contractile dysfunction does not correlate with an elevated intracellular free [Mg2+]: a 31P-NMR study on isolated rat and rabbit hearts. 828 65

Magnesium has been reported as an effective medical therapy in an expanding array of conditions. Evidence investigating magnesium's use is presented, with a number of studies suggesting it should be seriously considered in such conditions as ischemic heart disease, cardiac arrhythmias, and asthma. Magnesium balance and metabolism are briefly reviewed, and then various hypotheses are presented that may explain magnesium's physiologic mechanisms of action, most likely involving calcium and potassium flux across cellular membranes in smooth muscle. In a number of the conditions to be discussed, it has been uncertain whether magnesium administration serves the purpose of merely correcting an underlying deficiency state or of utilizing a specific pharmacologic effect of magnesium. Magnesium deficiency is a relatively common condition, and predisposing factors as well as recent methods for assessing total body stores of magnesium are discussed. Physicians should be familiar with the numerous conditions and therapeutics that are risk factors for an underlying magnesium deficiency and in which empiric magnesium replacement should be considered. Guidelines for administration of parenteral magnesium are presented with specific focus on the low risk of adverse effects, as suggested by the large and rapid dosing regimens used in many of the clinical studies discussed here.
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PMID:Magnesium and its therapeutic uses: a review. 830 65

Myocardial ischemia leads to significant changes in the intracellular and extracellular ionic milieu, high-energy phosphate compounds, and accumulation of metabolic by-products. Changes are measured in extracellular pH and K+, and intracellular pH, Ca2+, Na+, Mg2+, ATP, ADP, and inorganic phosphate. Alterations of membrane currents occur as a consequence of these ionic changes, adrenergic receptor stimulation, and accumulation of lactate, amphipathic compounds, and adenosine. Changes in the volume of the extracellular and intracellular spaces contribute further to the ultimate perturbations of active and passive membrane properties that underlie alterations in excitability, abnormal automaticity, refractoriness, and conduction. These characteristic changes of electrophysiologic properties culminate in loss of excitability and failure of impulse propagation and form the substrate for ventricular arrhythmias mediated through abnormal impulse formation and reentry. The ability to detail the changes in ions, metabolites, and high-energy phosphate compounds in both the extracellular and intracellular spaces and to correlate them directly with the simultaneously occurring electrophysiologic changes have greatly enhanced our understanding of the electrical events that characterize the ischemic process and hold promise for permitting studies aimed at developing interventions that may lessen the lethal consequences of ischemia.
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PMID:Electrophysiologic changes in ischemic ventricular myocardium: I. Influence of ionic, metabolic, and energetic changes. 858 73

Magnesium ions (Mg2+) are pivotal in the transfer, storage and utilization of energy; Mg2+ regulates and catalyzes some 300-odd enzyme systems in mammals. The intracellular level of free Mg2+ ([Mg2+]i) regulates intermediary metabolism, DNA and RNA synthesis and structure, cell growth, reproduction, and membrane structure. Mg2+ has numerous physiological roles among which are control of neuronal activity, cardiac excitability, neuromuscular transmission, muscular contraction, vasomotor tone, blood pressure and peripheral blood flow. Mg2+ modulates and controls cell Ca2+ entry and Ca2+ release from sarcoplasmic and endoplasmic reticular membranes. Since the turn of this century, there has been a steady and progressive decline of dietary Mg intake to where much of the Western World population is ingesting less than an optimum RDA. Geographic regions low in soil and water Mg demonstrate increased cardiovascular morbidity and mortality. Dietary deficiency of Mg2+ results in loss of cellular K+ and gain of cellular Na+ and calcium ions (Ca2+). Blood normally contains Mg2+ bound to proteins, Mg2+ complexed to small anion ligands and free ionized Mg2+ (IMg2+). Most clinical laboratories only now assess the total Mg, which consists of all three Mg fractions. Estimation of the IMg2+ level in serum or plasma by analysis of ultrafiltrates (complexed Mg + IMg2+) is somewhat unsatisfactory, as the methods employed do not distinguish the truly ionized form from Mg2+ bound to organic and inorganic anions. Because the levels of these ligands can vary significantly in numerous pathological states, it is desirable to directly measure the levels of IMg2+ in complex matrices such as whole blood, plasma and serum. Using novel ion selective electrodes (ISE's), we have found that there is virtually no difference in IMg2+, irrespective of whether one samples whole blood, plasma or serum. These data demonstrate that the mean concentration of IMg2+ in blood is about 600 mumoles/litre (0.54-0.65 mmol/L, 95% Cl); 65-72% of total Mg being free or biologically-active Mg2+. Use of the NOVA and KONE ISE's for IMg2+ on plasma and sera from patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants, liver transplants, during and before cardiac surgery, ischemic heart disease [IHD], headaches, pregnancy, neonatal period, non-insulin dependent diabetes (NIDDM), end-stage renal disease [ESRD], hemodialyse [HEM], and continuous ambulatory peritoneal dialysis (CAPD), hypertension, myocardial infarction [AMI] and after excessive dietary intake of Mg), has revealed interesting data. The results indicate that long-term renal transplant patients, headache, pregnant, NIDDM, ESRD, HEM, CAPD, AMI, hypertensive, and IHD subjects exhibit, on the average significant depression in IMg2+ but not TMg. Use of 31P-NMR spectroscopy on red blood cells, from several of these disease states, to assess free intracellular Mg ([Mg2+]i demonstrates a high correlation (r = 0.5-0.8) between IMg2+ and [Mg2+]i. Increased dietary load of Mg, for only 6 days, in human volunteers, resulted in significant elevations in serum IMg2+ but not TMg. Correlations between the clinical course of several of the above disease syndromes and the fall in IMg2+ and [Mg2+]i were found. The ICa2+/IMg2+ ratio appears, from our data, to be an important guide for signs of peripheral vasoconstriction, ischemia or spasm and possibly atherogenesis. Overall, our data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.
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PMID:Role of magnesium in patho-physiological processes and the clinical utility of magnesium ion selective electrodes. 886 38

In this review, a rationale is presented for how hypercholesterolemia, hypertension, diabetes mellitus, end-stage renal disease, renal dialysis, and prolonged stress can all lead to atherosclerosis, ischemic heart disease, and stroke. The data indicate that Mg deficiency caused either by poor diet and/or errors in Mg metabolism may be a missing link between diverse cardiovascular risk factors and atherosclerosis. Data from our laboratories and others indicate that reduction in extracellular and intracellular free Mg ions (Mg2+) can induce an entire array of pathophysiological phenomena known to be important in atherogenesis, that is, vasospasm, increased vascular reactivity, elevation in [Ca2+]i, formation of proinflammatory agents, oxygen radicals, platelet aggegation, reduction in cardiac bioenergetics, cardiac failure, oxidation of lipoproteins, gender-related modulation of endothelial-derived relaxing factor/NO, changes in membrane fatty acid saturation, changes in membrane plasmalogens and N-phospholipids (suggesting changes in intracellular phospholipid signals), and probably transcription factors.
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PMID:Magnesium and cardiovascular biology: an important link between cardiovascular risk factors and atherogenesis. 886 81

In myocardial ischemia, pHi and [ATP] fall, whereas the free [Ca2+] and [Mg2+] rise. The effects of these changes on cardiac Ca2+ release channel (ryanodine receptor) activity were investigated in [3H]ryanodine binding and single-channel measurements, using isolated membrane and purified channel preparations. In the absence of the two channel ligands Mg2+ and ATP, cardiac Ca2+ release channels were half-maximally activated at pH 7.4 by approximately 4 mumol/L cytosolic Ca2+ and half-maximally inhibited by approximately 9 mmol/L cytosolic Ca2+. Regulation of channel activity by Ca2+ was modulated by Mg2+ and ATP. Single-channel activities were more sensitive to a change of cytosolic pH than SR lumenal pH. Reduction in lumenal and/or cytosolic pH from 7.3 to 6.5 and 6.0 resulted in decreased single-channel activities without a change in single-channel conductance. [3H]Ryanodine binding measurements also indicated that acidosis impairs cardiac Ca2+ release channel activity. Mg2+ and adenine nucleotide concentrations regulated the extent of inhibition and the Ca2+ dependence of binding. In the presence of 5 mmol/L Mg2+ and 5 mmol/L beta, gamma-methyleneadenosine 5'-triphosphate (AMPPCP, a nonhydrolyzable ATP analogue), the free [Ca2+] for half-maximal [3H]ryanodine binding was increased from 1.9 mumol/L at pH 7.3 to 36 mumol/L at pH 6.5 and to 89 mumol/L at pH 6.2. These results suggest that ionic and metabolic changes that might be expected to affect sarcoplasmic reticulum Ca2+ release channel activity in ischemic myocardium include an altered Ca2+ sensitivity of the channel, a fall in pH, and a loss of the high-energy adenine nucleotide pool, leading to an increased inhibition by Mg2+.
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PMID:Regulation of cardiac Ca2+ release channel (ryanodine receptor) by Ca2+, H+, Mg2+, and adenine nucleotides under normal and simulated ischemic conditions. 894 48

Epidemiological studies associate low dietary magnesium intake with an increased incidence of ischemic heart disease and sudden cardiac death. We have used proton-magnetic resonance (1H-NMR) techniques and Mg2+-selective electrodes to monitor changes in lipid extracts of aortic and cerebrovascular smooth muscle as extracellular ionized magnesium ion concentration ([Mg2+]o) is lowered. We have found that, within the pathophysiological range of Mg2+ concentrations, fatty acid chain length and double bond content are progressively reduced as [Mg2+]o is lowered. In contrast, the plasmalogen content is progressively increased. A concomitant decrease in fatty acid chain length and double bonds indicates oxidation of double bonds resulting in truncation of the fatty acids. A decrease in lipid oxidation in the presence of elevated Mg2+ could contribute to the apparent protective role of increased Mg2+ intake on vascular function in humans.
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PMID:Mg2+ modulates membrane lipids in vascular smooth muscle: a link to atherogenesis. 918 65

Interrelations between hypertension (HT), ischemic heart disease (IHD) and diabetes mellitus (DM) were investigated in the diabetic subjects without IHD (DM group) or with IHD (DM + IHD group) and subjects with IHD (IHD group) which were not complicated with DM. 1. The incidence of hypertension of DM group, DM+IHD group and IHD group is 40, 54, 38% respectively. 2. The incidence of hyperlipidemia of DM group, DM + IHD group and IHD group is 55, 71, 56% respectively. 3. Serum Mg levels of DM (1.9 +/- 0.37 mg/dl), DM + IHD (1.8 +/- 0.23) and IHD (1.9 +/- 0.33) were significantly lower than that of normal control (2.3 +/- 0.32). 4. Serum Mg level of poorly controlled diabetic patients is lower than that of well controlled diabetic patients. These results suggested that Magnesium deficient state is one of the cause of insulin resistancy.
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PMID:Hypertension and serum Mg in the patients with diabetes and coronary heart disease. 924 Jul 68


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