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)

Endothelin-1 concentrations were measured in peripheral venous blood samples from 42 patients with acute myocardial infarction. In patients with ischemic or hemodynamic complications (n = 11), endothelin-1 concentrations were significantly higher already on admission (P = 0.008) and remained significantly higher until day 6 after admission compared to patients with uncomplicated infarctions (n = 31; P = 0.035). There were no close correlations between peak concentrations of endothelin-1 and creatine kinase or creatine kinase isoenzyme MB mass in either group. Only in complicated patients did left ventricular ejection fraction correlate closely and inversely with peak endothelin-1 concentrations (r = -0.71; P = 0.03). Therefore, plasma endothelin-1 concentrations in patients with acute myocardial infarction patients may reflect states of markedly depressed cardiac performance and recurrent myocardial ischemia.
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PMID:Endothelin-1 in patients with complicated and uncomplicated myocardial infarction. 146 30

Endothelin-1 (ET-1) is a recently described potent vasoconstrictor peptide. Plasma and myocardial tissue levels of ET-1 are increased following myocardial ischemia, however, the factors which regulate ET-1 binding sites in vivo are not well understood. ET-1 binding sites were measured by Scatchard analysis of [125I]ET-1 binding to membranes of rat myocardium. The highest number of ET-1 binding sites (2,951 fmol/mg protein) were found in right atrial tissue, and followed the rank order of right atrium greater than left atrium (2,157 fmol/mg protein), greater than right ventricle (835 fmol/mg protein), greater than septum (609 fmol/mg protein) = left ventricle (498 fmol/mg protein). Following coronary artery occlusion for 24 h, ET-1 binding sites of left atrium were decreased by 35% (p less than 0.01), without a change in the Kd (i.e., 98 pM). Other regions of the myocardium did not exhibit any change in the number of ET-1 binding sites. Similarly, no change in ET-1 binding sites were observed following coronary artery occlusion for 0.5 h followed by 24 h reperfusion. These data indicate that there exists considerable regional differences in the density of ET-1 binding sites in the myocardium, and that ET-1 sites are selectively reduced in left atrial tissue following myocardial infarction.
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PMID:Identification of cardiac endothelin binding sites in rats: downregulation of left atrial endothelin binding sites in response to myocardial infarction. 166 22

Endothelin-1 (ET-1) has been shown to induce severe ventricular arrhythmias associated with myocardial ischemia. However, ET-1 may have a direct arrhythmogenic action that is not related to myocardial ischemia. To examine this possibility, we studied the electrophysiological effects of ET-1 on cardiac tissues. The right bundle branch, false tendon, ventricular muscle, and atrial muscle were isolated from the dog, and transmembrane potentials were recorded by the conventional microelectrode technique. ET-1 prolonged the action potential duration (APD) in all of the tissues tested except in the atrial muscle, where the APD was shortened. Bay K 8644, a calcium channel agonist, prolonged the APD in all cardiac tissues. Spontaneous firing of the right bundle branch was suppressed by ET-1 but not Bay K 8644. The prolongation of the APD by ET-1 was far more marked in the right bundle branch than in other tissues, and it was followed by the development of early after depolarizations (EADs) only in the right bundle branch. The EADs induced by ET-1 or Bay K 8644 were abolished by nicardipine. These data suggest that L-type calcium current is involved in the genesis of EADs by ET-1, although other ionic mechanisms can not be ruled out. Since EADs underlie some types of arrhythmias, arrhythmias caused by ET-1 are at least partly attributable to the direct actions of the agent on myocardial cells.
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PMID:Electrophysiological effects of endothelin-1 on canine myocardial cells. 172 17

The effects of intracoronary-administrated endothelin-1 on coronary hemodynamics and regional myocardial function were studied in anesthetized open-chest dogs. Epicardial coronary diameter (CoD) and coronary blood flow (CBF) were measured by a sonomicrometer of 10 MHz piezoelectric crystals and an electro-magnetic flow probe on the left circumflex coronary artery (LCX). Regional wall motion was sonomicrometrically measured at regions supplied by the LCX and left anterior descending artery (LAD) and electrocardiograms were recorded. Endothelin-1, administered as a bolus injections into the LCX via an intracoronary cannula, in a dose-dependent manner reduced COD and CBF. The extent of the reduction of COD and CBF at a dose-dependent manner reduced COD and CBF. The extent of the reduction of COD and CBF at a dose of 300 pmol was 12.3 +/- 1.5% (P less than 0.01) and 86 +/- 5% (P less than 0.01), respectively, of the control. The extent of CBF reduction and deterioration of systolic wall motion were linearly related with the dosage of endothelin-1. ST-elevation (lead II) and fatal ECG abnormalities, including complete atrioventricular block or ventricular fibrillation, were observed with doses above 60 and 100 pmol, respectively. Coronary angiography revealed that filling defects of dye were propagated from the third or distal branches to those of more proximal arteries when the doses of endothelin-1 were cumulatively infused into the LCX. Accordingly, lethal myocardial ischemia induced by endothelin-1 is produced by critical obstruction of rather small coronary vessels.
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PMID:Effects of endothelin-1 on epicardial coronary tone, coronary blood flow, ECG-ST change and regional wall motion in anesthetized dogs. 180 Apr 77

Endothelin is a novel endothelium-derived vasoactive peptide with potent vasoconstrictor action in the coronary bed; however, its possible contribution to myocardial ischemia and infarction is not known. Plasma endothelin-1 concentration was measured with use of a radioimmunoassay in serial venous samples from 22 patients over a 72 h period after acute myocardial infarction (14 patients with uncomplicated infarction [group I] and 8 patients with hemodynamic or ischemic sequelae [group II]). Twenty-two normal subjects and seven patients with stable angina served as the control subjects. Endothelin-1 levels in patients with stable coronary disease were not different from those of normal subjects (0.62 +/- 0.56 and 0.76 +/- 0.38 pg/ml, respectively). In group I, plasma levels of endothelin-1 rose sharply after myocardial infarction, reaching a peak of 4.95 +/- 0.78 pg/ml at 6 h after the onset of chest pain (p less than 0.05 compared with values in control subjects) and returning rapidly toward the normal range by 24 h. Patients with complicated infarction (group II) demonstrated a similar rapid increase in plasma endothelin-1 to a peak value of 8.29 +/- 1.95 pg/ml; however, plasma endothelin-1 remained elevated in these patients, becoming significantly different from values in group I at 48 and 72 h. There was no correlation between peak increases in creatine kinase and peak endothelin-1 in either group, suggesting that the stimulus for elevation of endothelin-1 was not myocardial necrosis itself. Furthermore, left ventricular ejection fraction did not correlate with the increase in endothelin-1 in group I patients, whereas there was a significant inverse relation between ventricular function and plasma endothelin-1 in group II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased plasma endothelin-1 in the early hours of acute myocardial infarction. 205 Sep 38

The purpose of this study was to determine the effects of endothelin-1 on the coronary vascular bed of closed chest pigs. Endothelin-1 (3 to 30 pmol/kg body weight) was selectively administered into the left anterior descending coronary artery. Coronary blood flow and epicardial vessel diameter were measured by quantitative arteriography. Arterial pressure increased after a 30 pmol/kg dose and heart rate was not changed. Coronary blood flow and vessel diameter of the left anterior descending artery significantly decreased by 74% and 32%, respectively (p less than 0.01 versus control) after the 30 pmol/kg dose, whereas these variables modestly decreased in the left circumflex artery. Endothelin-1 in doses of 10 to 30 pmol/kg produced electrocardiographic ST segment elevation associated with decreased oxygen saturation of coronary sinus venous blood. Endothelin-induced coronary vasoconstriction was significantly inhibited after treatment with intravenous diltiazem (0.2 mg/kg, n = 6) or nifedipine (0.1 mg/kg, n = 5), but not after vehicle administration (n = 4). This study demonstrates that intracoronary administration of endothelin-1 causes significant myocardial ischemia through coronary vasoconstriction, which is inhibited by a calcium channel blocker. The data suggest that calcium influx into the smooth muscle cells appears to be involved at least in part in the mechanism of endothelin-induced coronary vasoconstriction in vivo.
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PMID:Effects of calcium channel blockers on coronary vasoconstriction induced by endothelin-1 in closed chest pigs. 222 78

The endothelium modulates coronary vascular tone by the release of endothelium-derived relaxing or contracting substances. The endothelium-derived relaxing factor has been identified as nitric oxide synthesized in endothelial cells from L-arginine. The endothelium can release other relaxing substances such as prostacyclin and a hyperpolarizing factor. Endothelin-1 is a potent vasoconstrictor peptide formed by endothelial cells, and is likely to be the physiologic antagonist of endothelium-derived relaxing factor. Other putative contracting factors include superoxide anions and products of arachidonic acid metabolism. Endothelium-derived relaxing factor is released spontaneously and in response to flow, platelet-derived products (that is, serotonin, thrombin and adenosine diphosphate) and certain autacoids (that is, acetylcholine, bradykinin, histamine, substance P, vasopressin, alpha-adrenergic agonists). A considerable heterogeneity of responses exists among vessels of different size from different anatomic origin and different species. Hypercholesterolemia, atherosclerosis, hypertension and myocardial ischemia or reperfusion, or both, impair endothelium-dependent relaxation. Under normal conditions, endothelium-derived relaxing factor appears to dominate the control of vascular tone of large and small coronary vessels, whereas in disease states, endothelium-derived contracting factors are released. Impairments of endothelial function may be important in the development of various forms of cardiovascular disease.
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PMID:Endothelial control of vascular tone in large and small coronary arteries. 240 18

Endothelin-1, the most potent endothelium-derived vasoconstrictor peptide identified so far, exerts multiple biologic effects that are potentially relevant for the pathogenesis of coronary atherosclerosis and ischemic heart disease. Since the discovery of the peptide, a good deal of experimental and clinical data have been accumulated to support an important role of endothelin-1 in ischemic heart disease. In experimental animals, exogenous endothelin-1 was found to cause coronary vasoconstriction and, at higher doses, ventricular fibrillation and death. Endothelin receptor subtypes have been demonstrated and pharmacologically characterized in the coronary vascular bed. The plasma levels of immunoreactive endothelin-1 were found to be increased in patients with coronary atherosclerosis, acute myocardial infarction, and angina. Given its growth-promoting and mitogenic action, endothelin-1 has also been suspected to participate in the mechanism of restenosis after PTCA. The purpose of this study was to critically review the experimental and clinical data supporting the involvement of endothelin-1 in ischemic heart disease and the results of more recent studies on the effects of endothelin-1 blockade on experimental myocardial necrosis and restenosis after PTCA.
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PMID:Endothelin-1: a scientist's curiosity, or a real player in ischemic heart disease? 896 76

The purpose of this study was to determine the antagonistic effect of tetramethyl pyrazine (TMP), a sort of chinese herbal medicine, on coronary vasoconstriction induced by endothelin-1 (ET-1) in closed chest dogs. ET-1 at doses of 50, 75 and 100 pmol was selectively administered into left main coronary artery and coronary angiogram was performed in 1, 3 and 10 minutes after intracoronary administration of ET-1. After a 60 minute interval ET-1 administration and coronary angiogram were repeated in two groups in group A with 5 dogs intravenous infusion of saline solution was administered while in group B with 4 dogs TMP was infused at a dose of 80 mg/kg. Blood pressure of intra-femoral artery, heart rate and ECG were monitored during the experiment. The study demonstrated that coronary vessel diameter significantly decreased by 17% (P < 0.02) in group A and 20% (P < 0.02) in group B, associated with ischemia in ECG (4/5 in group A and 3/4 in group B) after intracoronary administration of ET-1. Endothelin-1 induced coronary vasoconstriction and ischemic changes in ECG were significantly inhibited by intravenous TMP. The coronary diameter increased by 20% (P < 0.03) after administration of TMP, comparing with the control group. Heart rate had an increased response to TMP. In conclusion this study demonstrated that intracoronary administration of ET-1 caused significant myocardial ischemia through coronary vasoconstriction, which was inhibited by TMP. TMP significantly dilated coronary artery.
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PMID:[Effect of tetramethyl pyrazine on coronary vasoconstriction induced by endothelin-1 in dogs]. 920 4

Endothelin-1 (ET-1) is a peptide hormone with potent vasoconstrictor properties that is synthesized and secreted predominantly by vascular endothelial cells. Its production is regulated by numerous stimuli including ischemia and hypoxia, and the enhanced levels that occur during myocardial ischemia may contribute to the progression of heart failure. We previously reported that ET-1 expression was induced by both hypoxia and transition metals in endothelial cells (ECs). Here we define an element in the proximal promoter of the ET-1 gene that is responsible for this induction. By using deletions and site directed mutagenesis of the human ET-1 promoter, in combination with electrophoretic gel mobility shifts and transient expression assays in human ECs, we identified an active hypoxia-inducible factor 1 (HIF-1) binding site starting at position -118 upstream of the transcription start site on the non-coding DNA strand. Mutation of this site eliminated induction by hypoxia without affecting basal (aerobic) expression, and the mutated sequence did not display hypoxia-specific binding of HIF-1.
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PMID:Hypoxia regulates expression of the endothelin-1 gene through a proximal hypoxia-inducible factor-1 binding site on the antisense strand. 958 11


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