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)

alpha-adrenergic stimulation of patients with ischemic heart disease should intuitively impose a destructive stress. However, therapeutic alpha1-adrenergic receptor mediated cardioadaptation prior to myocardial ischemia protects ventricular mechanical function, promotes electrophysiologic stability, and preserves myocyte viability. Prior to an anticipated cardiac ischemic insult, alpha1-adrenergic preconditioning attenuates ischemic myocardial acidosis by a protein kinase C-(PKC) dependent mechanism. The alpha1-adrenoceptor can directly stimulate calcium-independent nPKC isoforms via diacylglycerol (DAG) or indirectly stimulate calcium-dependent cPKC isoforms through the release of intracellular calcium via inositol triphosphate, (IP3). We hypothesized that alpha1-adrenergic limitation of ischemic acidosis is mediated by the family of calcium-dependent PKC isoforms. [31P]NMR spectra were obtained in isolated, buffer perfused rat hearts treated with alpha1-adrenergic stimulation [phenylephrine (PE) 50 microM, 2 min]; PKC blockade [chelerythrine chloride, (Chel) 20 microM]; or stearoyl-arachidonoyl glycerol (SAG, a DAG analogue, 100 microM, 2 min) administered 10 min prior to ischemia. Control hearts were perfused under normoxic conditions for 20 min. All hearts were then subjected to global ischemia (20 min, 37.5 degrees C). Developed pressure (DP) and heart rate were recorded continuously. pHi was obtained from chemical shift of inorganic phosphate. Immunohistochemical staining was utilized to delineate the translocation and activation profiles of specific PKC profiles established with each stimulus. Pre-ischemic alpha1-adrenergic stimulation did attenuate the myocellular hydrogen ion accumulation during sustained normothermic ischemia (6.90 +/- 0.13 vs control 6.54 +/- 0.10; P < 0.05). General PKC inhibition abrogated this effect (end-ischemic pH 6.17 +/- 0.10; P < 0.05 vs control and PE). Ischemic acidosis was not attenuated following selective nPKC stimulation (SAG, 6.48 +/- 0.08; NS vs control). Myocellular immunohistochemical staining revealed translocation of the calcium-independent PKC-epsilon isoform in the calcium-dependent PKC (SAG) group, but not in response to alpha1-adrenergic stimulation. The results suggest that (1) alpha1-adrenoceptor stimulation limits ischemic acidosis, (2) alpha1-adrenergic stimulated attenuation of ischemic acidosis is PKC dependent, (3) direct nPKC stimulation with SAG does not limit ischemic acidosis, and (4) SAG stimulates nPKC-epsilon isoform activation where alpha1-adrenergic stimulation does not. We conclude that alpha1-adrenergic stimulation limits ischemic acidosis by a cPKC-dependent mechanism and that the mobilization of the IP3 arm by receptor stimuli suppresses PKC-epsilon thus permitting the limitation of ischemic acidosis.
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PMID:Alpha-adrenergic preservation of myocardial pH during ischemia is PKC isoform dependent. 866 Dec 19

The beneficial effects of n-3 polyunsaturated fatty acids of fish oil in the prevention of fatal arrhythmias in myocardial ischemia were suggested to be at least in part mediated by a modulation of dihydropyridine-sensitive L-type calcium channels. As cardiac alpha 1-adrenoceptor stimulation has been suggested to have no significant effect on L-type calcium channels, the aim of this study using cultured neonatal rat cardiomyocytes was to investigate whether chronic n-3 polyunsaturated fatty acid exposure may have an influence on alpha 1-adrenoceptor-induced positive inotropic effects and induction of arrhythmias. Pretreatment of the rat cardiomyocytes for 3 days in the presence of the n-3 polyunsaturated fish oil-derived fatty acid docosahexaenoic acid (60 mumol/l) markedly decreased alpha 1-adrenoceptor-stimulated increase in contraction velocity and induction of arrhythmias. The increase in contraction velocity of the cardiomyocytes induced by the beta-adrenoceptor agonist isoprenaline was also markedly reduced by the n-3 fatty acid pretreatment. Basal contractile amplitude and spontaneous beating frequency of the cardiomyocytes were not significantly altered by the docosahexaenoic acid exposure. The pretreatment of the rat cardiomyocytes for 3 days in the presence of docosahexaenoic acid (60 mumol/l) decreased alpha 1-adrenoceptor-stimulated formation of the calcium-mobilizing second messenger IP3 and its metabolites IP2 and IP1 by 55%. The depression of IP3 formation by docosahexaenoic acid treatment was not mediated by a decreased uptake of myo-inositol into the cardiomyocytes nor by a decreased synthesis of phosphatidylinositol bisphosphate (PIP2), the substrate of phospholipase C. The level of glycerol-3-phosphate, an important substrate of the phosphoinositide cycle, was unaltered by the docosahexaenoic acid pretreatment. Receptor binding studies revealed that the dissociation constant and maximal binding capacity of the alpha 1-adrenoceptor antagonist (3H)prazosin was unchanged by the n-3 polyunsaturated fatty acid exposure. Beta-Adrenoceptor-and forskolin-stimulated adenylyl cyclase activities were not diminished by the docosahexaenoic acid pretreatment. Chronic exposure of the cardiomyocytes to the n-6 polyunsaturated fatty acid arachidonic acid (60 mumol/l) did neither significantly alter alpha 1-adrenoceptor-induced inositol phosphate formation nor alpha 1-adrenoceptor-stimulated increase in contraction velocity. The results presented show that chronic n-3 polyunsaturated fatty acid pretreatment of rat cardiomyocytes leads to a marked impairment of alpha 1-adrenoceptor-induced positive inotropic effects and induction of arrhythmias concomitant with a n-3 fatty acid-induced decrease in IP3 formation. This derangement of the phosphoinositide pathway by chronic n-3 fatty acid exposure may, thus, contribute to the beneficial effects of fish oil-derived fatty acids in the prevention of fatal arrhythmias in myocardial ischemia.
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PMID:Exposure to the n-3 polyunsaturated fatty acid docosahexaenoic acid impairs alpha 1-adrenoceptor-mediated contractile responses and inositol phosphate formation in rat cardiomyocytes. 885 87

These preclinical studies investigate a new concept in coronary angioplasty and balloon catheter technology (the P100 catheter). The study sought to evaluate the morphology of experimental coronary arterial plaques dilated with the P100 in comparison to standard balloons, to determine the in vitro flow rates occurring during the inflation of the P100 in comparison to available perfusion catheters, and to assess the in vivo coronary flow velocity and the presence of ischemia during prolonged inflations with the P100. The development of myocardial ischemia is a major limitation of standard balloon angioplasty. To limit ischemia, autoperfusion catheters have been developed, in which blood flows through the balloon in the central catheter shaft. However, as the flow lumen profile is reduced to enhance the performance of these devices, so is the accompanying flow. An angioplasty catheter was designed to evaluate the feasibility of continuous autoperfusion around the dilatation balloon. The balloon surface was engineered to develop a helical trough for blood flow to occur during inflation. Arterial plaque morphology following angioplasty with the P100 (n = 8) and with standard balloons (n = 8) was evaluated in a swine model. In vitro flow rates during inflation of the P100 and available perfusion catheters were determined using 33% glycerol solution. In vivo coronary flow velocity was determined with a Doppler-tipped wire during 60-min continuous inflations with the P100, and 15-sec inflations with a standard balloon in 12 vessel segments in 7 dogs; using 3.0-3.5-mm-diameter balloons. All lesions were successfully dilated (< 50% luminal diameter stenosis) with the P100 and standard balloons. There were no morphologic differences in plaques dilated with P100 compared to standard balloons. In vitro flow rates with conventional 3.0-mm balloon perfusion catheters ranged from 27.1 +/- 2.1 ml/min (RX Flowtrack) to 38.7 +/- 0.9 ml/min (Stack Perfusion), P < .05. Flow with the P100 ranged from 54.8 +/- 4.3 ml/min (2.5-mm balloon) to 103.2 +/- 4.5 ml/min (3.5-mm balloon), P < .05. Distal average peak coronary flow velocity during prolonged P100 inflations varied from 69 +/- 7% of baseline at 5 min to 83 +/- 8% of baseline at 40 min, with an upward trend in velocity the longer the balloon was inflated. Hemodynamics remained stable. Experimental plaques are successfully dilated with a helical balloon by a mechanism that appears similar to the dilatation mechanism of standard balloons. These preclinical studies show that angioplasty and autoperfusion can be accomplished by a balloon that does not have complete surface area contact with the vessel wall. A gap created by the helix can thus provide a conduit for blood flow. Clinical studies will determine whether this innovation, which alters the tubular geometry of current angioplasty balloons, will provide autoperfusion and equivalent dilatation effects in human.
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PMID:New concept in coronary angioplasty: dilatation with a helical balloon that allows simultaneous autoperfusion. 899 27

A new method in quantitative determination of double bonds (DB) in the pool of fatty acids (FA) has been worked out by ozone titration after extraction of lipids according to Folch. A correlation was observed among DB content, the level of cholesterol alcohol (CS, r = +0.612; p < 0.001) and the level of glycerol (GL) alcohol (r = +0.392; p < 0.01). The grown-ups with ischemic heart disease and children have a constant ratio (5.05 +/- 0.18) DB:CS ratio.
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PMID:[Proportion of alcohols of cholesterol, glycerol and double bonds of fatty acids in blood serum and lipoproteins. Diagnostic significance of hypercholesterolemia]. 1258 44

The beneficial effects of pyruvate in organ reperfusion injury have been documented, however the therapeutic use of pyruvate has been hindered by the lack of an appropriate delivery method. Pyruvic acid is unstable and high rates of sodium pyruvate infusion are toxic. Dipyruvyl-acetyl-glycerol (DPAG) ester was developed as a novel method for intravenous pyruvate delivery at a high rate without sodium overload. We tested the ability of DPAG to reduce myocardial infarct size when administered after severe myocardial ischemia in an anesthetized open-chest pig model of ischemia-reperfusion injury. Ischemia was induced by total occlusion of the distal 2/3 of the left anterior descending coronary artery for one hour, followed by two hours of reperfusion. Animals were either untreated (n = 7), or treated with intravenous DPAG (8.0 mg/kg(-1). min(-1), n = 8) during the two hours of reperfusion. Infarct size was measured on blinded samples using tetrazolium staining. The DPAG treated group had elevated pyruvate levels (0.82 +/- 0.07 mM) and reduced infarct size (20.1 +/- 4.2% of the volume at risk, compared to 30.8 +/- 4.6% in the untreated animals (p < 0.05)), with no difference in blood pressure or heart rate between groups. In conclusion, an intravenous infusion of DPAG safely increases arterial pyruvate concentration and reduces myocardial infarct size following myocardial ischemia.
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PMID:Post-ischemic treatment with dipyruvyl-acetyl-glycerol decreases myocardial infarct size in the pig. 1457 79

Abstract Introduction: Intracoronary shunting is a useful, easy and inexpensive technique to maintain blood flow during off-pump surgery to lessen myocardial ischemia. Intracoronary shunts should provide a minimal flow for adequate myocardial protection. Material and Methods: Two commercially available shunts were used to measure flow from a bulb-size diameter of 1.00 mm to 3.00 mm (n = 10) in an in vitro setup. Shunts were perfused with Glycerin 47% solution at 37 degrees C. Inlet pressure was raised continuously from 0 to 160 mmHg in all intracoronary shunts. Results: In both groups (recipients of either type A shunt or type B shunt), mean pressure of 40 mmHg was necessary in shunts with diameter of 3.0 mm to provide a flow of approximately 50 mL/min. At mean pressure of 100 mmHg, a maximum flow of 126 mL/min was measured. Shunt B of 2.5-mm and 3.0-mm diameter showed similar flow patterns: 50 versus 52 mL/min at 40 mmHg and 98 versus 108 mL/min at 100 mmHg. Shunt A at 2.5-mm diameter showed 37 mL/min at 40 mmHg and 80 mL/min at 100 mmHg ( P =.01). Shunt B at 1.5-mm diameter required 75 mmHg for approximately 40mL/min and showed maximum flow of 51 mL/min at 100 mmHg ( P <.001). Only minimal flow was measured in 1.0-mm shunts of both groups. Conclusions: There is a clear pressure/flow correlation in 2.0-mm to 3.0-mm shunts with maximum flow of 126 mL/min. Type B shunt of 1.5-mm and 2.5-mm diameter showed significant better flow rates. The possible value of 1.0-mm shunts is only in stenting and facilitating anastomosis and to obtain better visibility during anastomosis.
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PMID:Validation of Intracoronary Shunt Flow Measurements for Off-Pump Coronary Artery Bypass Operations. 1498 Aug 45

Exercise provides numerous salutary effects, but our understanding of how these occur is limited. To gain a clearer picture of exercise-induced metabolic responses, we have developed comprehensive plasma metabolite signatures by using mass spectrometry to measure >200 metabolites before and after exercise. We identified plasma indicators of glycogenolysis (glucose-6-phosphate), tricarboxylic acid cycle span 2 expansion (succinate, malate, and fumarate), and lipolysis (glycerol), as well as modulators of insulin sensitivity (niacinamide) and fatty acid oxidation (pantothenic acid). Metabolites that were highly correlated with fitness parameters were found in subjects undergoing acute exercise testing and marathon running and in 302 subjects from a longitudinal cohort study. Exercise-induced increases in glycerol were strongly related to fitness levels in normal individuals and were attenuated in subjects with myocardial ischemia. A combination of metabolites that increased in plasma in response to exercise (glycerol, niacinamide, glucose-6-phosphate, pantothenate, and succinate) up-regulated the expression of nur77, a transcriptional regulator of glucose utilization and lipid metabolism genes in skeletal muscle in vitro. Plasma metabolic profiles obtained during exercise provide signatures of exercise performance and cardiovascular disease susceptibility, in addition to highlighting molecular pathways that may modulate the salutary effects of exercise.
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PMID:Metabolic signatures of exercise in human plasma. 2050 14

The present study was carried out to examine whether acute experimental myocardial infarction affects the sympathetic transmission to vessels and the heart of pithed rats via a presynaptic mechanism and, if so, to check whether inhibitory presynaptic cannabinoid (CB) receptors and endocannabinoids are involved in this response. In pithed and vagotomized rats, electrical stimulation (0.75 Hz; 1 ms; 50 V; 5 or 15 pulses for increases in heart rate or blood pressure, respectively) of the preganglionic sympathetic nerve fibers or intravenous injection of isoprenaline (0.1 nmol/kg) or noradrenaline (1 nmol/kg) increased heart rate and blood pressure by approximately 50 beats/min and 40 mm Hg, respectively. Ligation of the left coronary artery reduced the electrically (as opposed to the chemically) induced tachycardic and pressor responses by approximately 30 to 40%. The inhibitory effect of myocardial infarction was prevented by the CB(1) receptor antagonist rimonabant but not by the CB(2) receptor antagonist N-[(1S)-endo-1,3,3-trimethyl-bicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyra-zole-3-carboxamide (SR144528) and the transient receptor potential vanilloid 1 receptor antagonist capsazepine. The inhibitory effect of myocardial infarction was slightly enhanced by the inhibitors of anandamide and 2-arachidonyl glycerol degradation, 3'-(aminocarbonyl)[1,1'-biphenyl]-3-yl)-cyclohexylcarbamate (URB597) and 4-nitrophenyl-4-(dibenzo[d][1,3]dioxol-5-yl(hydroxy)methyl)piperidine-1-carboxylate (JZL184), respectively. Rimonabant increased myocardial infarction-induced mortality. Our results demonstrate that during the early phase of myocardial infarction the activation of presynaptic CB(1) receptors by endogenously formed cannabinoids contributes to the inhibition of the neurogenic tachycardic and vasopressor responses. Thus, the CB(1) receptor-mediated inhibition of excessive noradrenaline release from the sympathetic nerve fibers innervating the heart and vessels might play a protective role in myocardial ischemia.
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PMID:Acute myocardial infarction inhibits the neurogenic tachycardic and vasopressor response in rats via presynaptic cannabinoid type 1 receptor. 2279 98

Aquaporins are a group of proteins with high-selective permeability for water. A subgroup called aquaglyceroporins is also permeable to glycerol, urea and a few other solutes. Aquaporin function has mainly been studied in the brain, kidney, glands and skeletal muscle, while the information about aquaporins in the heart is still scarce. The current review explores the recent advances in this field, bringing aquaporins into focus in the context of myocardial ischemia, reperfusion, and blood osmolarity disturbances. Since the amount of data on aquaporins in the heart is still limited, examples and comparisons from better-studied areas of aquaporin biology have been used. The human heart expresses aquaporin-1, -3, -4 and -7 at the protein level. The potential roles of aquaporins in the heart are discussed, and some general phenomena that the myocardial aquaporins share with aquaporins in other organs are elaborated. Cardiac aquaporin-1 is mostly distributed in the microvasculature. Its main role is transcellular water flux across the endothelial membranes. Aquaporin-4 is expressed in myocytes, both in cardiac and in skeletal muscle. In addition to water flux, its function is connected to the calcium signaling machinery. It may play a role in ischemia-reperfusion injury. Aquaglyceroporins, especially aquaporin-7, may serve as a novel pathway for nutrient delivery into the heart. They also mediate toxicity of various poisons. Aquaporins cannot influence permeability by gating, therefore, their function is regulated by changes of expression-on the levels of transcription, translation (by microRNAs), post-translational modification, membrane trafficking, ubiquitination and subsequent degradation. Studies using mice genetically deficient for aquaporins have shown rather modest changes in the heart. However, they might still prove to be attractive targets for therapy directed to reduce myocardial edema and injury caused by ischemia and reperfusion.
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PMID:Cardiac aquaporins. 2415 93


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