Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The blocking of the creatinphosphokinase by 1-fluoro-2,4-dinitrobenzene (FDNB) allows to investigate the relationship between ATP-supply, contractility and relaxability of the frog's myocardium. In isotonically working isolated ventricles of frogs the time of work, systolic and diastolic volume, velocity of contraction and relaxation as well as the levels of CP, ATP, ADP and AMP were measured at different intervals until termination of each experiment. CP shows a small variation, ATP decreases to 60% and ADP + AMP increase for the same amount under FDNB during the development of a slight inhibition of contractility and a continuously growing inhibition and retardation of relaxation until systolic arrest. ATP content and volume of relaxation correlated strictly. The contracture and the diminished contractility are caused by the decrease of ATP, producing a lack of substrate for Ca transport and actin-myosin-ATPase. This models the course of events during an insufficiency like in angina pectoris and in myocardial infarction.
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PMID:[Mechanical characteristics of isotonic work and high-energy phosphates in frog ventricle after 1-fluoro-2,4-dinitrobenzene]. 31 Jun 11

There is no established treatment specifically aimed at protecting or restoring cardiac energy metabolism, which is greatly impaired by ischaemia. Even after reperfusion, myocardial content of ATP remains low for more than 72 h. Long-term post-ischaemic dysfunction and irreversibility of ischaemic damage have been associated with low ATP content. Evidence that the pentose sugar ribose stimulates ATP synthesis and improves cardiac function led us to test the possibility that ribose increases tolerance to myocardial ischaemia in patients with coronary artery disease (CAD). 20 men with documented severe CAD underwent two symptom-limited treadmill exercise tests on 2 consecutive days; we postulated that the ischaemia induced might bring about changes in ATP metabolism lasting for several days. Patients whose baseline tests showed reproducibility were randomly allocated 3 days of treatment with placebo or ribose 60 g daily in four doses by mouth. Exercise testing was repeated after treatment on day 5. At that time mean (95% confidence interval) treadmill walking time until 1 mm ST-segment depression was significantly greater in the ribose than in the placebo group (276 [220-331] vs 223 [188-259] s; p = 0.002). The groups did not differ significantly in time to moderate angina. In the ribose-treated group the changes from baseline to day 5 in both time to ST depression and time to moderate angina were significant (p less than 0.005), but these changes were not significant in the placebo group. In patients with CAD, administration of ribose by mouth for 3 days improved the heart's tolerance to ischaemia. The presumed effects on cardiac energy metabolism offer new possibilities for adjunctive medical treatment of myocardial ischaemia.
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PMID:Effects of ribose on exercise-induced ischaemia in stable coronary artery disease. 135 76

The activity of potassium, sodium, magnesium and Ca-ATP-ase of the erythrocytic membrane, index of erythrocyte deformability, changes of the hemodynamics and some cardiac function during bicycle ergometry [correction of veloergometry] tests before and after a course of laser irradiation of the blood were studied in 36 patients with exertion stenocardia. It was established that laser therapy is accompanied by increase of the activity of ATP-ase, index of erythrocyte deformability and positive changes of the cardial function. The possibility is discussed of improving the cardiac function under the effect of laser irradiation as a result of optimization of the structural-functional organization of the cellular membrane.
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PMID:[The effect of laser irradiation of the blood on the adenosine triphosphatase activity of the erythrocyte membranes and on the cardiac activity indices in patients with ischemic heart disease]. 145 31

Seven patients with angina pectoris and 201-thallium scintigraphy indicative of myocardial perfusion defects, but with normal coronary angiograms, were investigated. Metabolic events were studied in biopsies from myocardium and skeletal muscle (m. quadriceps femoris). Profound metabolic derangement was evidenced by a distinctly lowered energy charge in myocardium (0.88 +/- 0.04 in controls vs. 0.48 +/- 0.09 in patients; P less than 0.001) and skeletal muscle (0.92 +/- 0.01 in controls vs. 0.70 +/- 0.09 in patients; P less than 0.01). Accordingly, low values were recorded for ATP in both types of muscle, where ATP was lower than (myocardium) or the same as (skeletal muscle) ADP. The concentration of myocardial lactate was 115 +/- 74 mumol g-1 dry weight and that of skeletal muscle lactate was 11 +/- 3 mumol g-1 dry weight, compared to normal myocardial lactate of 18 +/- 10 mumol g-1 dry weight and normal skeletal muscle lactate of 11 +/- 3 mumol g-1 dry weight. Unprecedentedly low energy charge levels in both cardiac and skeletal muscle biopsies suggest that a systemic metabolic disease is highly probable. An inverse ATP/ADP ratio found in our patients is indicative of an aetiology different from ischaemia, which would not produce this relationship.
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PMID:Angina pectoris patients with normal coronary angiograms but abnormal thallium perfusion scan exhibit low myocardial and skeletal muscle energy charge. 840 42

The normal control of coronary blood flow is through alterations in the resistance of the intramyocardial arterioles (R2). Myocardial cellular hypoxia causes increased breakdown of ATP (or decreases synthesis) resulting in increased concentrations of the purine metabolite, adenosine. This potent endogenous, vascular smooth muscle relaxant vasodilates the R2 arterioles increasing coronary blood flow and myocardial O2 delivery. This mechanism autoregulates coronary blood flow according to myocardial O2 needs. Myocardial hypertrophy (from chronic hypertension) or coronary atherosclerosis interfere with this process and result in myocardial ischemia which may cause symptoms (angina), signs (ECG changes, regional muscle dysfunction) or tissue death (myocardial infarction). In addition, coronary atheroma disrupt endothelial function in the large R1 coronary arteries predisposing to vasoconstriction, platelet aggregation and thrombosis. Therapeutic measures for controlling ischemia may include decreasing oxygen demand (especially heart rate) and maintaining supply (R1 vasodilators and anti-thrombotic drugs such as non-steroidal anti-inflammatories). Intravenous, most inhalational and regional anesthesia appear to interfere minimally in the control of both the normal and ischemic coronary circulation. Thus optimizing myocardial oxygen balance (maintaining supply and decreasing demand) during anesthesia protects the ischemic myocardium. High doses of isoflurane, sevoflurane or desflurane are potent R2 coronary vasodilators which may cause redistribution of collateral blood flow away from ischemic regions (coronary steal). However, if tachycardia and hypotension are avoided, such an effect has not been shown experimentally or clinically. Preliminary evidence suggests that halothane may preferentially dilate R1 arteries and/or interfere with platelet aggregation. If these effects are confirmed, then halothane may prove to be the anesthetic of choice in the non-failing ischemic heart.
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PMID:Physiology, pathophysiology and pharmacology of the coronary circulation with particular emphasis on anesthetics. 164 43

The recent advances in cardiovascular pathophysiology have changed our interpretation of the interplay between myocardial metabolism and contractile function which takes place during acute ischemia. For instance, the use of nuclear magnetic resonance (NMR) spectroscopy has allowed to document that the rapid impairment in contractility seen during acute myocardial ischemia is not directly related to depletion of high energy phosphate levels, nor to decreased availability of intracellular calcium. Rather, acidosis and inorganic phosphate accumulation cooperate to decrease myofilament sensitivity to calcium. Marked alterations of cardiac function and metabolism may also accompany the postischemic period. Positron emission tomography studies have shown that myocardial uptake of glucose remains disproportionately elevated in areas of myocardium which have been rendered transiently ischemic by an episode of stress-induced angina in patients with coronary artery disease. This phenomenon may have important practical applications, as it may be used as a metabolic marker to detect areas of myocardium which is viable, but potentially at risk for ischemic episodes. Reduced ATP levels are another biochemical alteration which can be typically found in postischemic hearts. Again, NMR spectroscopy has allowed to establish that these hearts often display near-normal mitochondrial function, and that the delayed resynthesis of ATP is due to lack of purine nucleotide precursors. A most interesting functional peculiarity of postischemic hearts is represented by the prolonged impairment of contractility, which largely outlasts the duration of the period of flow deprivation. This phenomenon, which eventually subsides over the course of hours or days, has been termed myocardial stunning, to underline its occurrence despite the absence of ultrastructural signs of irreversible damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Metabolic changes and their mechanical consequences in acute myocardial ischemia]. 184 94

Angina is characterized by brief periods of ischemia followed by reperfusion; the cumulative effect of these episodes on energetics of the myocardium has not been fully elucidated. This study used an in vivo feline model for the assessment of high-energy phosphate compounds during brief sequential periods of ischemia and reperfusion. Nine adult, open-chest, anesthetized cats were prepared with a reversible occluder around the proximal left anterior descending artery and a 1.2-cm-inside diameter coil sutured on the myocardial surface in the distribution of the left anterior descending coronary artery. Levels of PCr, Pi, and ATP (beta-phosphate signal) were measured by 31P MRS in a GE CSI 2-T NMR spectrometer/imager. Measurements were obtained during a control period and during three successive occlusion-deocclusion periods of roughly 12 and 20 min' duration, respectively. The last deocclusion period was observed for 60 min. Electron microscopy was performed in two animals. PCr declined (P less than 0.01) rapidly following each occlusion to 51 +/- 5.2% (occlusion 1), 53 +/- 5.8% (occlusion 2), and 48 +/- 5.7% (occlusion 3) of the control value by 6 min. Pi rose (P less than 0.01) with the three sequential occlusions to 253 +/- 46, 288 +/- 57, and 277 +/- 46%, respectively. PCr and Pi returned to baseline promptly with reperfusion, while ATP showed a gradual decline throughout the experiment, decreasing to 77 +/- 7.2% of control at the end of the last reperfusion (P less than 0.05). Although PCr returned to baseline during reperfusion, ATP did not, suggesting a reduction in the nucleotide pool. These findings indicate that the repeated episodes of ischemia, which are insufficient to produce necrosis, can have an effect on myocardial high-energy phosphate metabolism as evidenced by mild depletion of ATP.
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PMID:Effect of repetitive brief episodes of cardiac ischemia on 31P magnetic resonance spectroscopy in the cat. 237 1

Perhexiline is a lysosomotropic agent which has proved to be very valuable to certain patients suffering from angina pectoris. However long-term administration of the drug may induce hepato- and neuro-toxicity. Using HTC cells (a rat hepatoma-derived cell line) whose plasma membranes were labeled with NaB[3H]4 after oxidation by NaIO4, endocytosis and recycling of labeled asialo-orosomucoid (ASOR) receptors were investigated in the presence of 50 mumols/l perhexiline maleate. The results demonstrate that the drug induces a significant decrease of the rate of both the internalization and the recycling of ASOR receptors. The mechanisms responsible for these effects have not yet been elucidated. However, the current findings may be related to the previously observed inhibitory effect of perhexiline on cellular (Na+, K+)-ATPase and Mg++-ATPase activities. Our findings would then reflect insufficient cellular energy production, resulting from depressed ATP hydrolysis in the presence of perhexiline.
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PMID:Effects of perhexiline maleate on asialo-orosomucoid receptor endocytosis and recycling in HTC cells. 261

Myocardial ischaemia results from complex interrelated processes involving progression of atherosclerosis, thrombosis, coronary spasm, platelet aggregation and local release of products from the arachidonic acid cascade. Endothelium-dependent responsiveness contributes to the local regulation of coronary blood flow, and the presence of endothelial damage may result in enhanced contraction of the smooth muscle. Drugs which have been used for the treatment of angina pectoris are able to reduce myocardial oxygen consumption. This concept will further be developed in the near future with beta-blocking agents with vasodilating properties, potent long acting nitrates (nicorandil), bradycardic agents (AQA 39 or AS-AH 208), and new calcium antagonists. However, future prospects in the treatment of angina pectoris include: drugs modifying the arachidonic acid cascade by increasing synthesis or release of prostacyclin (nafazatrom) or decreasing prostacyclin degradation (almitrine), or blocking thromboxane A2 synthetase (dazoxiben) or thromboxane A2 receptors (BM 13177) or, blocking the lipoxygenase pathway (nafazatrom) or prostacyclin analogues (iloprost); more clot-specific thrombolytic agents and new oral anticoagulant drugs; free-radical scavengers such as superoxide dismutase, catalase or peroxidase and drugs inhibiting xanthine-oxidase; anti-platelet drugs such as ticlopidine which blocks the fibrinogen receptors of platelets; drugs preventing the progression of atherosclerosis lesions such as nifedipine or verapamil in animals fed high-lipid diets; drugs which could modify myocardial metabolism during ischaemia. In this context, trimetazidine acts through prevention of ischaemia-induced decrease in ATP cellular storages, inhibition of potassium leak, decrease in free-radical production and thromboxane A2 synthesis and increase in prostacyclin synthesis. These new concepts provide an important contribution to the understanding of the pathophysiology of myocardial ischaemia. This explains the considerable development of pharmacological research for new agents in the treatment of angina pectoris.
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PMID:[Treatment of angina pectoris. New perspectives]. 294 45

Recent advances in the understanding of vascular physiology have furnished new aspects in the treatment of angina pectoris by various vasodilators. Upon stimulation by various factors (viscous drag from increased flow, pulsatile stretch, ADP/ATP, norepinephrine, serotonin), the coronary endothelium releases a vasodilator called endothelium-derived relaxant factor (EDRF). This factor has recently been shown to probably be nitric oxide (NO), which is identical to the active compound of nitroglycerin. EDRF (NO) dilates both large epicardial arteries and also coronary resistance vessels. It also has a strong platelet antiaggregant effect. The predominant effect of Ca2+ antagonists is on resistance vessels, increasing myocardial perfusion and viscous drag acting upon the endothelial lining. This, in turn, stimulates EDRF (NO) release in epicardial arteries and dilation. This additional nitrate-like effect augments the direct vasodilator effect of Ca2+ antagonists. Lack of normal endothelial function results in diminished capacity to dilate, and sometimes even in a shift from dilator to constrictor effects, paralleled by an increased tendency for platelet adhesion, activation, and thrombosis, which is still enhanced when plasma low density lipoprotein (LDL) is augmented. EDRF release, vasodilator capacity, and antiaggregant effects are reduced when LDL is high. Nitrates have a direct, endothelium-independent dilator effect, particularly on large coronary arteries, which seems even more pronounced when the endothelium is absent, but only when the vessel segment is still compliant. Therefore nitrates may particularly be effective in vessels with deficient EDRF release.
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PMID:Interdependence of pharmacologically-induced and endothelium-mediated coronary vasodilation in antianginal therapy. 315 91


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