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)

Theophylline-induced variations of cardiac metabolism have been investigated by determining concentrations of various energetic substrates and of high-energy phosphates in myocardial tissue, the repeated sampling of myocardium being made possible by an extracorporal circulation system. When administered in therapeutic, or even slightly higher doses, theophylline does not modify triglyceride, glycerol and free fatty acid content or phosphocreatine and ATP content in subepicardial and subendocardial layers, but it does lower glycogen and raise lactate concentration. Consequently, the changes in anaerobic glycolysis due to myocardial ischemia may be enhanced if, as is probably the case, theophylline fails to restore the supply of oxygen.
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PMID:Myocardial biochemical modifications induced by theophylline with reference to its value as antianginal drug. 48 94

The effect of repeated local ischemia and reperfusion on myocardial metabolism and ventricular performance was studied in 12 open-chested pigs fasted overnight. Myocardial ischemia was induced by reduction of the flow in the left anterior descending coronary artery to 40% of control during 30 min. After 35 min of reperfusion a second 30-min occlusion period was started, again followed by a 35-min reperfusion period. At the end of both reperfusion periods coronary flow and coronary resistance had returned to control values. During control there was lactate uptake, but no significant uptake of glucose, free fatty acids (FFA), triglycerdies, glycerol and inosine. During the first occlusion period the heart released lactate and inosine, and used glucose and FFA. At the end of the first reperfusion period lactate uptake approached control values, but inosine was still released by 10 of the 12 animals. In the second ischemic period, glucose and FFA were again taken up. Lactate and inosine were released, but the production was much smaller than during the first occlusion period. Depletion of myocardial glycogen and high-energy phosphates could be responsible for this quantitatively different response. Necrosis may have played a role, although enzyme release was minimal and only observed after the second occlusion period. Heart rate, peripheral resistance and ventricular filling pressure were virtually unchanged throughout the course of the experiments. Maximum rate of fall of left ventricular pressure (min LVdP/dt) decreased during ischemia and did not recover during reperfusion. Changes in min LVdP/dt and cardiac output were more closely related than changes in max LVdP/dt and cardiac output. This model cannot be used for the study of interventions during myocardial ischemia in which the animal serves as its own control.
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PMID:Myocardial substrate utilization and hemodynamics following repeated coronary flow reduction in pigs. 52 55

In this preliminary study, 120 cord blood samples were subjected to a simple on-the-ward triglyceride screening procedure and 15 were designated as being high and another 15 randomly selected as controls. All the samples were then subjected to detailed biochemical analysis for fatty acid profiles and/or concentrations of free fatty acids, triglycerides (TG), phospholipids, cholesterol esters and glycerol. Eleven of the samples designated 'high' were associated with one or more of the following clinical conditions: family history of ischaemic heart disease, maternal starvation, fetal distress, light-for-dates babies and excessive weight gain during pregnancy. There was an association between high TG levels and high glycerol levels. The fatty acid pattern of the TG was altered when at abnormally high concentration, in particular oleic acid was increased relative to the others, and this was associated with an increase in cholesterol ester oleic acid. The possible mechanisms resulting in cord hypertriglyceridaemia are discussed.
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PMID:Cord blood hypertriglyceridaemia as an index of fetal stress: use of a simple screening test and results of further biochemical analysis. 63 98

Using electrocardiographic technique, the effect of a single hyperbaric oxygenation session (O2 pressure 1.5 atm, duration 40 min) in combination with antianginal drugs (nifedipine--20 mg, propranolol--40 mg, nitrong--6.5 mg, orally) on central hemodynamics and myocardial contractility has been studied in 35 patients with ischemic heart disease and angina pectoris of effort, NYHA functional class II-III. It has been shown that hyperbaric oxygenation reduced the degree of indirect hemodynamic effect of nifedipine, potentiated negative chronotropic and inotropic effects of propranolol and had no impact on the degree of hemodynamic effect of depot-glycerol trinitrate.
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PMID:[Hyperbaric oxygenation and antianginal preparations: the effect of a single combined use on the functional indices of the state of the heart in patients with angina pectoris]. 141 16

The abilities of endothelin-1 to cause cellular injury and to enhance the levels of inositol-1,4,5-triphosphate and the breakdown of [14C]arachidonate-labeled phospholipids have been examined in the isolated rat heart model. In 10 minutes, endothelin at 1 and 3 nM concentrations significantly increased the myocardial release of creatine kinase, suggesting endothelin-induced cell injury. The enhanced levels of myocardial inositol-1,4,5-triphosphate and diacyl glycerol by endothelin also suggest the increased breakdown of phosphatidylinositol-4,5-bisphosphate. In addition, endothelin also increased the degradation of other membrane phospholipids as observed by (1) a decrease in [14C]arachidonate radiolabel in phospholipids, (2) an increase in [14C]radiolabel in non-esterified fatty acids and triacyl glycerol, and (3) increased levels of non-esterified fatty acids. The potential role of endothelin-1 in myocardial ischemia-reperfusion injury is discussed.
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PMID:Endothelin stimulates degradation of phospholipids in isolated rat hearts. 184 59

Recently, we have demonstrated that myocardial sarcolemma is predominantly comprised of plasmalogen molecular species and that the plasmalogen metabolite 1-O-alk-1'-enyl-2-acyl-sn-glycerol (AAG) accumulates during myocardial ischemia despite substantial decreases in 1,2-diacyl-sn-glycerol (DAG) content. To elucidate the physiological significance of AAG accumulation during myocardial ischemia, rabbit myocardial protein kinase C was partially purified by DE-52 and high-performance hydroxylapatite chromatographies, and the potency of AAG as an activator of myocardial protein kinase C was assessed. Both AAG and 1-O-alkyl-2-acyl-sn-glycerol are potent activators of myocardial protein kinase C with obligatory requirements for physiological increments in free Ca2+ concentration. In contrast, a substantial amount of myocardial protein kinase C activity elicited by DAG was calcium independent. Concentration dependence of ATP for protein kinase C-mediated phosphorylation was identical utilizing either ether-linked diglycerides or DAG as activators, with maximal phosphorylation manifest at ATP concentrations two orders of magnitude less than those found in ischemic myocardium. Thus accumulation of AAG in ischemic myocardium in conjunction with increases in intracellular free Ca2+ concentration may synergistically activate protein kinase C and therefore modulate phosphorylation of proteins in specific subcellular loci.
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PMID:Activation of myocardial protein kinase C by plasmalogenic diglycerides. 215 13

The hormonal regulation and enzymatic basis of endogenous lipolysis in heart are not yet completely elucidated. The lysosomal fraction from rat heart appeared to be markedly enriched in triglycerides and a significant reduction in triglycerides in this fraction was found after prolonged perfusion or stimulation of lipolysis with glucagon. The enhanced rate of lipolysis, measured as glycerol release from the isolated perfused rat heart, was abolished 10-15 min after continuous glucagon administration. Omission of glucagon for another 60 min restored the ability of glucagon to stimulate lipolysis, indicating the limited availability of endogenous triglycerides and the presence of a transfer-system for triglycerides from a non-metabolically active pool to a metabolically active pool. The enhanced lipolysis induced by low-flow ischemia was found to be inhibited by the lysosomotropic agent methylamine (5 mM). Methylamine-perfusion during low-flow ischemia was accompanied by an increased recovery of myocardial triglycerides in the lysosomal fraction. The possible role of lysosome-like particles in myocardial triglyceride homeostasis was further investigated by studying the kinetics of uptake and degradation of labeled triglycerides by membrane-particles recovered in the subcellular fraction enriched with lysosomal marker enzymes. It appeared that isolated lysosomal membranes take up added triglycerides at an average rate of 30 nmoles/min/g protein. The bulk of these triglycerides taken up is stored whereas 20% is degraded to diglycerides and free fatty acids. More than 90% of the free fatty acids formed were released from the lysosomes into the supernatant. The uptake and degradation of triglyceride-filled liposomes by isolated myocardial lysosomes was inhibited during incubation with methylamine (5 mM). On the other hand, a lowering of pH during in vitro incubation increased the rate of uptake and degradation of added triglycerides by isolated lysosomes. These results indicate that lysosomes or lysosome-like particles are involved in the enhanced lipolysis during myocardial ischemia.
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PMID:Involvement of lysosome-like particles in the metabolism of endogenous myocardial triglycerides during ischemia/reperfusion. Uptake and degradation of triglycerides by lysosomes isolated from rat heart. 235 Mar 29

We investigated the mechanism of membrane phospholipid degradation during reperfusion of ischemic myocardium using isolated and perfused rat hearts. Thirty min of myocardial reperfusion after 30 min of normothermic global ischemia resulted in a significant decrease of phosphatidylcholine (PC) content associated with a small but significant increase in lysophosphatidylcholine (LPC) content. Myocardial ischemia for up to 60 min caused no significant loss of any of the major phospholipids. Isotopic incorporation of [14C]arachidonic acid (AA) as well as [3H]-glycerol into PC was significantly attenuated in the ischemic-reperfused heart compared with the normally perfused heart, suggesting that both reacylation and de novo pathways for PC synthesis were inactivated during reperfusion. In the heart prelabeled with [14C]AA, the radiolabeled PC was decreased significantly during reperfusion, associated with a small but significant increase in [14C]AA accumulation. The decreases of PC content and incorporation of [14C]AA into PC, as well as the increases of LPC content and the [14C]AA during reperfusion, were prevented by reperfusion with low Ca2+ (50 microM) buffer or by pretreatment with trifluoperazine (10 microM) or mepacrine (50 microM), but not with verapamil (1 microM). The inhibition of loss of PC was associated with significant diminution of creatine kinase release from the reperfused hearts. The present study indicates that the net loss of membrane phospholipids, especially with respect to PC during reperfusion, may result from 1) inhibition of reacylation of AA, 2) inhibition of de novo synthesis, and 3) stimulation of phospholipase activity. These results are consistent with an influx of Ca2+, although other interpretations are also possible.
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PMID:Mechanism of membrane phospholipid degradation in ischemic-reperfused rat hearts. 250 30

The effects of glycerol trinitrate (GTN), sodium nitroprusside and isoket on central hemodynamics, myocardial contractility and myocardial function have been compared. 65 patients with ischemic heart disease have been examined. All the patients were divided into 3 groups depending on the drug studied. GTN was administered sublingually at a dose of 0.5 mg, while sodium nitroprusside and isoket were infused at doses of 1.5 micrograms (kg min) and 400 micrograms/min, respectively. It has been shown that GTN and isoket effects on central hemodynamics were mainly mediated by their venodilating action and preload reduction, thus promoting to the improvement of the myocardial function. Hemodynamic effects of sodium nitroprusside on the cardiovascular system are mediated by its dilating action on the arterial bed and afterload reduction.
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PMID:[Comparative assessment of the effect of nitroglycerin, sodium nitroprusside and isoket on hemodynamics in patients with ischemic heart disease]. 250 11

Recent studies have demonstrated that ether-linked diglycerides are endogenous constituents of biologic tissues and accumulate during agonist stimulation (Daniel, L. W., Waite, M., and Wykle, R. L. (1986) J. Biol. Chem. 261, 9128-9132) and myocardial ischemia (Ford, D. A., and Gross, R. W. (1989) Circ. Res. 64, 173-177). Although protein kinase C previously had been thought to specifically require 1,2-diacyl-sn-glycerol (DAG) molecular species for activation, the present study demonstrates that purified rat brain protein kinase C is activated by naturally occurring ether-linked diglycerides (e.g. 1-O-hexadec-1'-enyl-2-octa-dec-9'-enoyl-sn-glycerol and 1-O-hexadecyl-2-octa-dec-9'-enoyl-sn-glycerol) with a similar dose response curve to that for DAG molecular species. Although in vitro assays demonstrated that DAG could partially activate protein kinase C in the absence of free calcium, activation by ether-linked diglycerides required free calcium concentrations found only in stimulated cells (greater than 1 microM [Ca2+]free). To substantiate these findings the alpha and beta isoforms of protein kinase C from rat brain cortical grey matter were resolved by hydroxylapatite chromatography. Although the beta isoform of protein kinase C was substantially activated by DAG in the absence of free calcium, activation by ether-linked diglycerides had an absolute requirement for physiologic increments in free calcium ion found in stimulated cells. Since ether lipids are localized in specific subcellular membrane compartments, accumulate during several pathophysiologic perturbations and are effective activators of protein kinase C with separate and distinct calcium requirements in comparison to DAG, these results suggest that ether-linked diglycerides are important and potentially specific biologic activators of one or more isoforms of protein kinase C.
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PMID:Activation of protein kinase C by naturally occurring ether-linked diglycerides. 276 45


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