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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The evaluation of myocardial metabolic changes in ischemic heart disease remains centered on the coronary sinus pacing and sampling techniques established over the last 25 years. Lactate remains the marker of choice for most institutions, though centers with more sophisticated laboratories will always be trying to improve on the sensitivity and specificity for ischemia, perhaps using ATP catabolites and nucleotides and measuring coronary sinus flow. The diagnostic value of lactate changes is limited and probably not superior to a well-conducted 12-lead treadmill exercise electrocardiogram test, but it does provide an objective marker for reliable further study and evaluation of interventions. It is almost certainly in the research context that metabolic studies have their place--evaluating drugs, surgery, or angioplasty and perhaps shedding light on obscure entities, such as chest pain with normal coronary arteries and cardiomyopathies. Attention to detail and simplicity of study are more likely to lead to valuable results rather than concentrating on the complexities. Each laboratory should establish the reproducibility of its results before commencing any procedures.
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PMID:Laboratory diagnosis of myocardial ischemia. 287 36

Changes in cytosolic free magnesium ion concentration (Mgi) during myocardial ischemia were measured by 19F NMR in perfused rat hearts loaded with fluorine-labeled derivatives of the magnesium chelator o-aminophenol-N,N,O-triacetate. The perfused rat hearts were loaded intracellularly with the appropriate magnesium indicator by perfusion with 200-400 ml of Krebs-Henseleit buffer containing 5 microM acetoxymethyl ester of the indicator. Basal Mgi concentrations measured by three different indicators averaged 0.85 +/- 0.10 mM (n = 9) and showed no correlation with the KD of the indicator used. 31P NMR measurements of the magnesium-dependent shift between alpha- and beta-phosphates of ATP demonstrate that there is no measurable lowering of Mgi during loading with fluorinated o-aminophenol-N,N,O-triacetate. Between 10 and 15 min of ischemia, Mgi rose nearly 3-fold to 2.1 +/- 0.4 mM. This increase in Mgi occurred over the same time course as the decrease in ATP. After 20 min of reperfusion with Krebs-Henseleit buffer, Mgi declined to 1.5 +/- 0.5 mM. This sustained elevation of Mgi above basal levels may inhibit calcium release from sarcoplasmic reticulum, thereby contributing to the well documented impairment of mechanical function that occurs after a reversible period of ischemia.
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PMID:Cytosolic free magnesium levels in ischemic rat heart. 292 24

The perfusion of canine cardiac muscle with 10 microM oligomycin produced a nearly 90% slowing of the net rate of tissue ATP depletion from 0.200 to 0.025 mumol X min-1 X g wet wt-1 of tissue during a subsequent myocardial autolytic interval during which tissue pH was held constant. Moreover, lowering the tissue pH during the autolytic process by 0.6 unit from approximately 6.8 to approximately 6.2 produced a nearly 60% slowing of the net rate of tissue ATP depletion from 0.200 to 0.087 mumol X min-1 X g wet wt-1. The pH dependence of the net rate of tissue ATP depletion (by an oligomycin-sensitive process) was that predicted from the mitochondrial ATPase pH-inhibition profiles reported earlier (J. Biol. Chem. 258: 9657-9661, 1983). When taken together with our observation that the mitochondrial ATPase comprises approximately 90% of the total of all of the ATP hydrolyzing activities present in cardiac muscle cells, data reported here suggest that the protonic inhibition of the mitochondrial ATPase plays a major role in regulating the rate of tissue ATP depletion during myocardial ischemia.
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PMID:Effects of oligomycin and acidosis on rates of ATP depletion in ischemic heart muscle. 293 13

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

The effects of two antianginal drugs, nicorandil and isosorbide dinitrate (ISDN), on metabolism and function of the ischemic myocardium were studied in a preparation of multiple coronary occlusions in barbital-anesthetized dogs. The preparation consisted of three 5 min occlusions of the left anterior descending coronary artery interspersed by 30 min of reperfusion. An equihypotensive dose of nicorandil (7.5 micrograms/kg/min) or ISDN (12.5 micrograms/kg/min) was infused 15 min before and during the second occlusion period. Hemodynamics, myocardial segment shortening (%SS), tissue blood flow, and myocardial oxygen consumption were determined throughout. Uptake of free fatty acids (FFA), glucose, and lactate were determined during control and ischemic periods. At the end of the final 30 min reperfusion period, biopsy samples of transmural tissue were taken for analysis of phosphocreatine, adenine nucleotides, and total tissue water content. No major hemodynamic changes were produced by either drug except for a 5 to 10 mm Hg decrease in mean aortic pressure. Compared with untreated and ISDN-treated hearts, hearts of dogs treated with nicorandil exhibited reversal of a significant increase in FFA uptake during recurrent ischemia. This was accompanied by an attenuation of the increase in oxygen extraction and CO2 production in the ischemic zone by nicorandil, but not by ISDN. Nicorandil, but not ISDN, improved %SS during reperfusion. Endocardial ATP and total adenine nucleotides were preserved in both nicorandil- and ISDN-treated hearts. Tissue edema was also attenuated by both compounds. Thus, nicorandil improved both function and metabolism during recurrent myocardial ischemia independent of a hemodynamic effect, whereas ISDN only attenuated the loss of adenine nucleotides and increase in tissue water.
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PMID:Salutary action of nicorandil, a new antianginal drug, on myocardial metabolism during ischemia and on postischemic function in a canine preparation of brief, repetitive coronary artery occlusions: comparison with isosorbide dinitrate. 295 76

The purpose of this investigation was to compare the biochemical responses of normal and streptozotocin (STZ) diabetic rat hearts to myocardial ischemia. As expected, left ventricular peak systolic pressure (LVPSP) declined with the onset of ischemia. The time required to reach 75% (LVPSP75) and 50% (LVPSP50) of baseline LVPSP100 was significantly (p less than 0.05) more rapid in diabetic and iodoacetate-treated hearts when compared to control animals. Diabetic rats experienced a significant (p less than 0.05) reduction in myocardial glycogen levels with ischemia. Despite enhanced glycogenolysis in diabetic rat hearts, cardiac lactate failed to accumulate in significant amounts. Overall, myocardial ATP and CP levels declined, but the reduction appears not to be associated with the fall in LVPSP. The results confirm that ventricular pressure development decreases rapidly following iodoacetate treatment. Similar declines in function were observed in the diabetic heart suggesting that glycolytic pathway inhibition and/or diminished glycolytic flux is responsible for the reduction in left ventricular pressure during myocardial ischemia.
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PMID:Biochemical and physiological responses of the diabetic rat heart to induced myocardial ischemia. 296

Recent studies have established a major role for oxygen-derived free radicals in post ischemic tissue injury to the intestine. During ischemia, there appears to be a calcium-triggered, protease-dependent conversion of the native xanthine dehydrogenase to a superoxide-producing xanthine oxidase. The catabolic degradation of ATP during ischemia provides an oxidizable substrate, hypoxanthine. On reperfusion, molecular oxygen is resupplied and a burst of superoxide production ensues, resulting in extensive tissue damage. The same mechanism appears to occur in myocardial ischemia. Xanthine dehydrogenase rapidly converts to the oxidase during nonperfusion in the rat heart. In the isolated perfused working rat heart model, 40 min of anoxia followed by reoxygenation results in substantial release of creatine kinase. The release of creatine kinase is blocked almost completely by pretreatment of the rats with allopurinol, a specific inhibitor of xanthine oxidase.
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PMID:Free radicals and myocardial ischemia. The role of xanthine oxidase. 298 6

Complete global myocardial ischemia or zero coronary arterial flow in dogs results in a series of well-defined changes which begin when the myocardium converts from aerobic to anaerobic metabolism. These processes continue until the myocardium dies. The products of anaerobic metabolism, chiefly glycolytic intermediates, inorganic phosphate, H+, and creatine, are produced intracellularly and accumulate in the tissue. Because the demand for high-energy phosphates (HEP) in the tissue exceeds the supply available from anaerobic glycolysis and HEP reserves, net ATP level declines, approaching zero after 100 min of ischemia at 37 degrees C. At this time, the changes in totally ischemic tissue in vitro are equivalent to those seen in myocytes irreversibly injured by severe ischemia in vivo. During reoxygenation after total ischemia, the resumption of effective contractile activity depends partly on the metabolic changes and degree of myocyte injury sustained during ischemia.
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PMID:Complete global myocardial ischemia in dogs. 304 98

Adenosine and ATP exert pronounced electrophysiologic actions on the mammalian heart including a negative chronotropic action on cardiac pacemakers and a negative dromotropic action on atrioventricular conduction. These actions are modulated by complex interactions of the two compounds with the autonomic nervous system. Since both adenosine and ATP are released from myocardial cells under physiologic and pathophysiologic conditions, they could play an important modulating role in cardiac electrophysiology. Indeed, studies during the last decade have yielded strong evidence for the role of adenosine in the genesis of specific arrhythmias associated with myocardial ischemia. Further studies are required to fully elucidate the mechanisms of actions of adenosine and ATP in vivo. These will undoubtedly enhance the understanding of the potential arrhythmogenic, as well as the antiarrhythmic actions of endogenous and exogenous adenosine and ATP.
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PMID:On the mechanisms of cardiac electrophysiologic actions of adenosine and adenosine 5'-triphosphate. 305 Oct 10

We investigated the influence of the thromboxane (TX) synthetase inhibitor HOE 944 (6-(5-Methylimidazol-1-yl)methyl-2-naphthoic acid-Hydrochloride), prostacyclin (PGI2) and indomethacin on reperfusion arrhythmias in isolated perfused ischemic rat hearts. HOE 944, PGI2 and indomethacin were perfused in a concentration of 1 x 10(-6), 5 x 10(-8) and 1 x 10 (-6) mol/l respectively (in vitro). In another set up rats were pretreated p.o. with a daily dose of 30 mg/kg for 7 days (ex vivo). Acute regional myocardial ischemia was induced in isolated working rat hearts by occlusion of the left coronary artery. Reperfusion commenced upon release of this occlusion which was invariably associated with ventricular fibrillations (VF). Perfusion with 1 x 10(-6) mol/l HOE 944 did not affect these arrhythmias. In contrast hearts from HOE 944 pretreated rats were protected against fibrillations (p less than 0.01). PGI2 perfusion was also protective against VF (p less than 0.01) whereas indomethacin perfusion aggravated VF. In the ischemic period cardiodynamics like left ventricular pressure (LVP), dp/dt max and coronary flow (CF) were improved in HOE 944 pretreated rat hearts. In the venous effluent the enzyme activities of lactate dehydrogenase (LDH) and creatine kinase (CK) as well as lactate production were decreased in the ischemic and reperfusion period. Myocardial tissue levels of ATP were distinctly increased and lactate levels decreased in HOE 944 pretreated rats, whereas glycogen and creatine phosphate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of the thromboxane synthetase inhibitor HOE 944, prostacyclin and indomethacin on reperfusion arrhythmias, cardiodynamics and metabolism in isolated ischemic rat hearts. 307 62


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