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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial ischemia results from an imbalance of energy supply and demand. Because of the essentially aerobic nature of myocardial metabolism and the high oxygen extraction from the blood, ischemia is usually equatable with limitation of blood supply. Coronary atherosclerosis is a patchy disorder, and therefore, ischemia usually occurs in segmental fashion throughout the topography of the heart. Ischemia is invariably seen earliest and most intensely in the deep or subendocardial layers of myocardium. Ischemia leads to biochemical disruption, including initiation of glycolysis, which in turn causes electrophysiological and mechanical disturbances. Myocardial ischemia can be induced naturally or experimentally in the human subject in a variety of ways, some of which have been studied in the laboratory.
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PMID:Myocardial ischemia. 18 72

Changes in steady-state levels of reduced pyridine nucleotide (PN) recorded by continuous monitoring of surface fluorescence were correlated with changes in physiological function of perfused rat kidneys when subjected to anoxia, ischemia, hypothermia, variations in perfusion pressure, inhibition of Na-K ATPase, and uncoupling of oxidative phosphorylation. Biphasic responses of PN reduction and oxidation during ischemic cycles at varying temperatures and anoxic cycles at different perfusion pressures demonstrated the presence of two different cell populations in the kidney cortex, those with sufficient oxygen and those without. The magnitude of PN fluorescence change during ischemia increased with decreasing temperature demonstrating better tissue oxygenation during hypothermia. The measurement of mitochondrial NADH oxidation in the perfused kidney during transitions from CO anoxia to normoxia was made possible by flash photolytic activation of mitochondrial electron transport. The half time for NADH oxidation (125 ms) was independent of the rate of oxygen delivery while the initial rate and extent of reaction was faster and steeper, respectively, at higher perfusion pressure, due to a better tissue oxygenation and faster CO washout.
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PMID:Oxygen delivery in perfused rat kidney: NADH fluorescence and renal functional state. 18 9

Primary prevention of death from ischemic heart disease requires further understanding of the pathogenesis of this disorder. Cellular defects of cholesterol metabolism may be more significant markers that serum lipid levels for the identification and treatment of atherosclerotic risk. Coronary spasm has been shown to be an important cause of ischemia in the presence and absence of atherosclerotic lesions. Careful manipulation of physiologic variables with vasodilator agents during cardiopulmonary bypass can substantially alter the myocardial oxygen supply-demand relation, thereby minimizing ischemic injury. The cellular basis for loss of mechanical function during ischemia and the factors that determine irreversible injury are yet unknown.
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PMID:Pathophysiology of myocardial infarction. 19 8

A direct, noninvasive method of assessing the oxidation-reduction potential of an intramyocardial respiratory chain component is described. The technique is based on the differences in spectral properties between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NADH). The tissue surface fluorescence from intracellular NADH may be measured and documented photographically. Noose occlusion of a coronary artery produced detectable NADH fluorescence in 15 seconds in the subtended ischemic epicardium. This fluorescence of reduced pyridine nucleotide resolved following 60 seconds of reperfusion of the ischemic myocardium. The reduction of epicardial NADH with ischemia is a rapid and reversible process. A subsequent noose reocclusion resulted in a reproducible pattern of fluorescence. The technique of NADH fluorescence photography appears superior to current methods of assessing tissue oxygen supply:demand.
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PMID:Evaluation of cardiac ischemia by NADH fluroescence photography. 20 34

In Langendorff-perfused rat hearts, the perfusion pressure was reduced from 100 cm H2O to 20 cm H2O for 30 minutes to produce a model of global ischemia with a residual oxygen uptake. The release of lactate dehydrogenase (LDH) and the occurrence of ventricular arrhythmias during reperfusion were dependent on the substrate. Glucose-perfused hearts had the highest rates of glycolytic ATP production (2.5 mumol/g per min) during ischemia with normal contents of tissue cyclic adenosine 3',5'-monophosphate (cAMP) and, during reperfusion, the release of LDH was lowest and severe ventricular arrhythmias did not occur. In pyruvate-perfused hearts, glycolysis was inhibited during ischemia, the rate of production of glycolytic ATP was only 0.5 mumol/g per min. and tissue cAMP doubled; during reperfusion, LDH release was 14-fold higher and ventricular arrhythmias were more severe. Total tissue contents of ATP and phosphocreatine were similar in glucose- and in pyruvate-perfused hearts. In hearts perfused with acetate, there was virtually no glycolytic ATP synthesized during the last 5 minutes of ischemia and cAMP increased further. Acetate- and palmitate-perfused hearts showed greatest release of LDH and had severest arrhythmias during reperfusion, suggesting that it was the metabolic and not the detergent effects of palmitate that were operating. Lipolysis was not a major factor in the cause of reperfusion LDH release. A role of glycolytic ATP in the maintenance of membrane integrity is postulated.
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PMID:Effects of substrates on tissue metabolic changes in the isolated rat heart during underperfusion and on release of lactate dehydrogenase and arrhythmias during reperfusion. 20 59

The energy production (heat + work) of cardiac muscle must be interpreted in terms of the major ATPases underwriting cardiac contraction; these are the Ca2+ and Na+-K+ transport ATPases and actomyosin ATPase. It is possible to apply the classical phenomenological subdivisions to cardiac energy production; when this is done, certain properties immediately distinguish cardiac muscle from skeletal muscle. Little or no temporal distinction exists between initial (anaerobic) and recovery (oxidative) metabolism. Even at temperatures as low as 20 degrees C most of the recovery heat is released within the time course of a single contraction. Cardiac muscle is characterized by a high resting heat rate, the magnitude of which varies between species and depends on the metabolic substrate. In isometric contractions there is a slightly curvilinear relationship between developed force and heat production. There is a tension-independent or activation component, the magnitude of which reflects the prevailing level of contractility and is probably associated with calcium release and retrieval. In isotonic contractions energy production is maximal when the muscle is heavily loaded but falls steeply when the size of the load is reduced. The enthalpy:load relation is probably similar to that found in twitch contractions of skeletal muscle working at room temperature or above; but, unlike for skeletal muscle, there are families of such curves: At any instant of time the relation depends upon the prevailing physiological conditions (e.g. stimulus rate, substrate supply, humoral agents, extracellular ionic concentrations, initial length). Cardiac energy production can be estimated by a variety of other techniques (such as high-energy phosphate utilization, oxygen consumption, and changes in tissue fluorescence related to pyridine nucleotide oxidation levels). At the present time there is considerable agreement between heat measurements and results obtained with these different techniques. We should like to conclude on a cautionary note. First, there is considerable variability in the properties of cardiac muscle from different species. Significant variations occur at nearly all levels of cellular function--e.g. shape of action potential, electrical and mechanical dependence upon stimulus history, mechanisms of excitation-contraction coupling, actomyosin ATPase activity, metabolic regulation, and differential sensitivity to anoxia or ischemia. Second, the types of contractions readily studied in isolated papillary muscles (i.e. isometric or isotonic twitches) may not necessarily be the best mechanical paradigms for understanding myocardial energetics in vivo. The particular geometric demands of individual research techniques require the use of a wide variety of myocardial preparations from a wide variety of species. This necessarily produces a pastiche view of cardiac muscle rather than an integrated picture of some hypothetically typical mammalian myocardium.
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PMID:Cardiac heat production. 21 64

The effect of curantil on the values of energy metabolism in different parts of the myocardium was studied on dogs with experimental myocardial infarction. Tissue respiration, the activity of Krebs' cycle enzymes, cytochrome oxidase, pentose phosphate cycle and glycolysis, and the content of glycogen and adenyl components were studied. It was established that curantil has a positive effect on energy processes, particularly in myocardial areas not involved in ischemia. It is suggested that activation of tissue oxidation enzymes, which improves oxygen utilization and increases ATP production, is among the mechanisms of the curantil effect. It is noted that curantil stimulates the synthesis of glycogen and inhibits its decomposition. The accumulation in the myocardium of AMP, the precursor of adenosine possessing a marked coronarolytic effect, is an important aspect of the drug's action.
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PMID:[Metabolic shifts in acute period of myocardial infarct and the possibility of their correction with curantil]. 22 32

Contractile dysfunction is characteristic of the acutely ischemic myocardium. This study was undertaken to assess the temporal relations between the onset of cell anoxia and ischemic contractile failure in isolated, isovolumetric contracting rabbit hearts. High speed epicardial fluorescence photography using reduced nicotinamide adenosine nucleotide (NADH) was used to identify areas of cell anoxia. The onset of ischemia was correlated with deterioration of pressure generation over the course of sequential 60 second coronary arterial occlusions. In the isovolumetric contracting rabbit heart, areas of ischemia were detected 2 seconds after coronary occlusion. Significant reduction in peak systolic pressure occurred at 6 seconds of ischemic time and pressure continued to decrease throughout the 60 second period of coronary occlusion. NADH accumulation indicates imbalance of myocardial oxygen supply and demand and the cessation of oxygen utilization by the mitochondria. The results of this study indicate that ischemia is detectable within 1 to 2 seconds after coronary occlusion and that ischemic ventricular dysfunction occurs several seconds thereafter. Myocardial oxygen reserve is negligible.
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PMID:Temporal relation between onset of cell anoxia and ischemic contractile failure. Myocardial ischemia and left ventricular failure in the isolated, perfused rabbit heart. 22 47

Changes in cortical extracellular potassium activity ([K+]0), NADH fluorescence, and oxygen consumption were studied in anesthetized cats during pentylenetetrazol seizures. The effects of partial ischemia induced by either hypotension or intermittent carotid artery occlusion on these parameters were investigated. Nonischemic seizures were characterized by gradual generalized decreases in cortical NADH fluorescence and increases in O2 consumption, along with rapid increases in [K+]0, which then usually fell slightly as the ictal discharge continued. Ischemic seizures, on the other hand, were accompanied by complex changes in NADH fluorescence, by smaller delayed maximal increases in O2 consumption that lasted beyond the end of ictal activity, and by more sustained increases in [K+]0. The decay of [K+]0 after the termination of seizures in both nonischemic and moderately ischemic animals was not a monoexponential function: plots of ln delta [K+]0 versus time showed an initial linear decline (of slope M1) that rather abruptly slowed (to slope M2) after 2 to 5 sec and then often increased to the original rate. Both M1 and M2 were proportionately decreased by ischemia. In addition, the rate of [K+]0 removal could be slowed by acute ischemia induced either during or after the end of ictal activity. The initial rate of postictal [K+]0 removal (M1) was found to be linearly and inversely related to the level of cortical NADH fluorescence at the time of seizure termination. The results of this study suggest that an O2-dependent transport mechanism plays a major role in the removal of [K+]0 during and following the termination of generalized pentylenetetrazol seizures in the cat.
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PMID:Effects of ischemia on the removal of extracellular potassium in cat cortex during pentylenetetrazol seizures. 22 67

In cerebral ischemia, brain oxygen supply is totally exhausted within seconds. This necessitates cessation of mitochondrial electron transfer and energy (ATP) production. After certain periods of ATP deficiency of from 5 to 90 min, irreversible damage of mitochondrial membranes occurs. This results in decreased mitochondrial function, characterized by inhibited State 3 respiratory rates, low respiratory control ratios, and inhibited Ca2+ transport activities. A 30-min recirculation period of the ischemic brain tissue induces total restitution of mitochondrial respiratory capacity after complete ischemia, but not after incomplete ischemia. Regional in situ measurements of brain pyridine nucleotide redox levels, tissue ATP, and lactate concentrations indicate variable metabolic responses of different brain regions to oligemia. Macroheterogeneity from region to region, as well as microheterogeneity within a region are demonstrated. Contrary to the effect of tissue ischemia involving reduced or zero cerebral blood flow and tissue oxygenation, sublethal hypoxia alone at normal or increased levels of blood flow induces adaptation of the mitochondrial enzyme system to a new level of respiratory capacity, without any indications of inhibited mitochondrial energy production. Acute hypoxia induces increased respiratory capacities within 30-60 min. Under chronic conditions, alterations of mitochondrial cytochrome concentrations accompany the increased respiratory capacities. Instead of the decreased efficiency of mitochondrial energy-producing mechanisms induced by ischemia, hypoxia induces increased efficiency of energy production.
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PMID:Mitochondrial function in cerebral ischemia and hypoxia: comparison of inhibitory and adaptive responses. 23 75


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