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)

(1) Metabolism is the link between myocardial blood flow and physiological performance of the heart. (2) Metabolic myocardial radiopharmaceuticals have the potential to identify metabolic alterations unique to a given intrinsic cardiac disease (e.g. cardiomyopathies), to assess acute metabolic changes or in delineating a specific chronic metabolic defect (e.g. coronary artery disease). (3) Two approaches can be employed to evaluate in vivo myocardial utilization of subtracts: (a) use of radiolabeled "physiologic" substrates e.g. positron emitting 11C-palmitic acid was successfully employed for assessing the in vivo metabolic sequelae of myocardial ischemia, infarction and cardiomyopathies, and (b) use of modified tracers which enter known metabolic pathways. However, because of their unique structure, metabolism of the tracer stops at a certain state thus leaving the radiolabel trapped in the cell, e.g. [18F]FDG for measuring glucose metabolic rate in the human brain and myocardium. (4) Among the radiopharmaceuticals for planar and single photon tomography, the para and the ortho isomers of 123I-phenyl iodoheptadecanoic acids and their beta-methyl derivatives are the most promising tracers for myocardial metabolic studies. (5) Ortho-(123I-phenyl)-pentadecanoic acid (o-IPPA) human myocardial uptake was rapidly and markedly elevated in well perfused segments; myocardial turnover was strikingly prolonged, suggesting some "trapping" phenomenon, resulting in excellent scintigrams. This is in contrast to the relatively shorter clearance of the para isomer from the myocardium. (6) 11C-Palmitic acid and [18F]FDG are the most widely used for PET scanning for following myocardial metabolism. The most important clinical application of these agents is predicting viability of ischemic myocardium. (7) A significant proportion of fixed perfusion defects seen on thallium studies can be demonstrated to be viable myocardium on PET scans using metabolic agents. If the markers of perfusion alone are relied on to assess tissue viability, the extent of salvageable myocardium may be underestimated. The demonstration of myocardial viability is crucial in the decision of the optimal treatment of the disease.
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PMID:Radiopharmaceuticals for studying cardiac metabolism. 215 88

Recently, we identified a novel calcium-independent, plasmalogen-selective phospholipase A2 activity in canine myocardial cytosol which represents the major measurable phospholipase A2 activity in myocardial homogenates (Wolf, R. A., and Gross, R. W. (1985) J. Biol. Chem. 260, 7295-7303). We now report the 154,000-fold purification of this phospholipase A2 to homogeneity through utilization of sequential anion exchange, chromatofocusing, affinity, Mono Q, and hydroxylapatite chromatographies. The purified enzyme had a molecular mass of 40 kDa, possessed a specific activity of 227 mumol/mg min, had a pH optimum of 6.4, and catalyzed the regiospecific cleavage of the sn-2 fatty acid from diradyl glycerophospholipids. The purified polypeptide was remarkable for its ability to selectively hydrolyze plasmenylcholine in homogeneous vesicles (subclass rank order: plasmenylcholine greater than alkyl-ether choline glycerophospholipid greater than phosphatidylcholine) as well as in mixed bilayers comprised of equimolar plasmenylcholine/phosphatidylcholine. Purified myocardial phospholipase A2 also possessed selectivity for hydrolysis of phospholipids containing arachidonic acid at the sn-2 position in comparison to oleic or palmitic acid. Taken together, these results constitute the first purification of a calcium-independent phospholipase with absolute regiospecificity for cleavage of the sn-2 acyl linkage in diradyl glycerophospholipids and demonstrate that myocardial phospholipase A2 has kinetic characteristics which are anticipated to result in the selective hydrolysis of sarcolemmal phospholipids during myocardial ischemia.
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PMID:Purification and characterization of canine myocardial cytosolic phospholipase A2. A calcium-independent phospholipase with absolute f1-2 regiospecificity for diradyl glycerophospholipids. 235 13

Prostacyclin biosynthesis is dramatically increased in patients with acute myocardial infarction. As palmitoylcarnitine accumulates during myocardial ischemia, the action of this metabolite on the endothelial production of prostacyclin was studied. Palmitoyl-L-carnitine (10-100 microM) enhanced the release of prostacyclin and free arachidonic acid from bovine aortic endothelial cells. This action was mimicked by lysophosphatidylcholine, but by none of the following compounds: acetylcarnitine, carnitine, palmitic acid, sphingosine, dihydrosphingosine and N-stearoyl-dihydrosphingosine. In addition to mobilizing free arachidonate, palmitoylcarnitine induced the release of free choline and phosphorylcholine presumably via the activation of phospholipases C and D. Palmitoyl-L-carnitine had also a cytotoxic effect on the endothelial cells. These data suggest that the increased biosynthesis of prostacyclin in myocardial infarction might be partially explained by the accumulation and release of palmitoyl-L-carnitine.
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PMID:Palmitoyl-L-carnitine increases the release of prostacyclin from vascular endothelial cells. 251 Jul 29

The risk factors for ischemic heart disease (IHD) in 35 Tibetan highlanders were investigated and compared with those in 30 age- and sex-matched healthy Japanese controls. Although Tibetans had remarkably high hematocrit values, and a decrease of eicosapentaenoic acid in both serum total lipids and serum phospholipid (PL) possibly due to their diet, they were considered to have a low incidence of IHD from our door-to-door study. These positive risk factors are likely counteracted by other negative risk factors as follows; Tibetans rarely exhibited systolic hypertension, and had lower levels of serum cholesterol and serum apolipoprotein (apo) B, and apo B/apo A-I ratio. In addition, Tibetan highlanders showed a decreased level of palmitic acid and an increased level of linoleic acid in serum PL which may protect against atherosclerosis.
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PMID:The risk factors for ischemic heart disease in Tibetan highlanders. 272 29

Previous studies have suggested that the accumulation of free arachidonic acid may be of major importance in the pathophysiology of myocardial ischemia. The purpose of the present study was to determine if the release of arachidonic acid from myocardial cells was more dependent on the extent of ATP depletion than on the inhibition of fatty acid oxidation. In addition, these studies were designed to determine if arachidonic acid release only occurred when ATP was depleted beyond a critical threshold level. To examine the relationship between arachidonic acid release and ATP depletion, cultured myocardial cells from neonatal rat hearts were labeled with [3H]arachidonate and [14C]palmitate. In response to ATP depletion with various metabolic inhibitors, [3H]arachidonic acid and [14C]palmitic acid were released from phospholipids. Phosphatidylcholine, phosphatidylethanolamine, and phosphatidic acid were the major esterified sources of the arachidonate. The release of both fatty acids was related to the extent of ATP depletion and not whether a glycolytic or respiratory inhibitor was utilized. Various combinations and doses of metabolic inhibitors were used, and experimental conditions that produced a greater than 75% decrease in ATP content were associated with the accumulation of arachidonic acid. These results suggest that an ATP-dependent step may be linked to the accumulation of arachidonic acid during myocardial ATP depletion. It is suggested that myocardial cells may release arachidonic acid directly in response to ATP depletion.
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PMID:Mechanisms of accumulation of arachidonic acid in cultured myocardial cells during ATP depletion. 393 86

Enzymatic pathways involved in the metabolism of lysophosphatidylcholine were investigated in rat heart myocardial cells. Acyl CoA-dependent acyltransferase activity was localized in microsomes, and was much greater than lysophospholipase activity in either cytosolic or microsomal fractions. The cytosolic lysophospholipase was more sensitive to inhibition by palmitylcarnitine in comparison to free fatty acids. In contrast, free fatty acids (oleate and palmitate) produced a greater inhibition of the microsomal acyltransferase and lysophospholipase than did palmitylcarnitine. A reduction in the assay pH to 6.5 resulted in an increase in microsomal acyltransferase and cytosolic lysophospholipase activities, but brought about a marked reduction in the microsomal lysophospholipase activity. At pH 6.5, the percentage inhibition of the microsomal acyltransferase by palmitylcarnitine was reduced, whereas the inhibition by palmitic acid was enhanced. The inhibition of the microsomal lysophospholipase by both palmitylcarnitine and palmitic acid was reduced at pH 6.5. With respect to myocardial ischemia, the inhibition of microsomal acyltransferase by free fatty acids and the reduction in microsomal lysophospholipase activity due to acidosis may contribute to the elevation of cellular lysophosphoglycerides which are arrhythmogenic.
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PMID:Regulation of lysophosphatidylcholine-metabolizing enzymes in isolated myocardial cells from rat heart. 407 68

Calcium entry into cardiac cells is believed to be controlled by transmembrane-voltage dependent, protein regulated "channels." The sarcoplasmic reticulum participates in the regulation of cytosolic calcium by ATP dependent Ca2+ sequestration during diastole, and by action potential stimulated calcium release. Massive calcium overloading occurs during reperfusion following myocardial ischemia. Calcium overloading activates phospholipases, which may activate another mechanism involved in lethal cellular injury, that is, the accumulation of long chain fatty acids and their derivatives. These compounds are soluble amphiphiles, and once liberated, they may insert into biological membranes and change membrane composition, physiology, and response to ions and drugs. Sarcoplasmic reticulum vesicles were used as an in vitro model to study the effects of palmitic acid, oleic acid, and palmitylcarnitine on the ability of this membrane system to sequester calcium within the vesicles. In the absence of phosphate, palmitic acid enhanced the ability of the vesicles to sequester calcium. Oleic acid and palmitylcarnitine inhibited calcium sequestration. In the presence of phosphate palmitic acid also inhibited the sequestration of calcium by sarcoplasmic reticulum, although not as severely as oleic acid and palmitylcarnitine. These results suggest that the disturbances in cellular calcium homeostasis following ischemia may be due, in part, to the incorporation of accumulated long chain fatty acids into membranes.
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PMID:The possible role of endogenous amphiphiles in the membrane abnormalities of ischemic and reperfused myocardium. 668 Jun 16

Thirty-two men who had recently had a myocardial infarction were matched individually for age with controls who had no evidence of heart disease. The patients had a significantly lower proportion of linoleic acid and a higher proportion of palmitic acid in their plasma triglyceride fatty acids. Analysis of the composition of red-cell membrane phosphatidyl choline, which reflects long-term dietary fat intake, showed a significantly lower proportion of linoleic acid in the patients.These differences suggest that the type of dietary fat consumed might be an important factor in the genesis of ischaemic heart disease.
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PMID:Low dietary intake of linoleic acid predisposes to myocardial infarction. 680 86

Positron-emission computed tomography (PCT) is a new means of studying regional myocardial metabolism. This new device permits quantitative, cross-sectional imaging of the tissue concentrations of positron-emitting tracers of blood flow and metabolism in the myocardium. To examine the potential value of PCT for evaluating regional alterations in myocardial metabolism, acute myocardial ischemia was induced by rapid atrial pacing in open-chest dogs with partial coronary stenoses. Regional myocardial glucose uptake and utilization of free fatty acids were examined with the glucose analog F-18 2-fluoro-2-deoxyglucose (FDG) and C-11-labeled palmitic acid. Myocardial blood flow was evaluated with N-13 ammonia. In the ischemic segment, uptake of C-11 palmitic acid was reduced in proportion to blood flow and its rate of clearance as an index of beta oxidation was delayed. There was a relative or absolute increase in FDG uptake (depending on the uptake of FDG in the normal myocardium). Similar observations were made in patients with ischemic heart disease and anginal symptoms at the time study. The observed alterations in the regional distribution of positron-emitting tracers of metabolic substrates in ischemic myocardium are in agreement with previously reported animal experimental studies in which a fall in free fatty acid utilization associated with an increase in glycolytic flux was observed. These studies indicate that metabolic alterations associated with acute myocardial ischemia observed previously in destructive animal experiments do indeed occur in humans and can now be demonstrated noninvasively in humans by PCT.
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PMID:Assessment of regional myocardial ischemia by positron-emission computed tomography. 697 56

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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