Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute myocardical ischemia was produced by ligating the midlevel left anterior descending coronary artery for 17 min in anesthetized dogs. Epicardial electrocardiograms were recorded from 15 sites surrounding the area of left anterior descending coronary artery ligation with a smooth tip, rounded epicardial electrode. Sites of ST segment elevation and isoelectric sites within the grossly ischemic portion of the left ventricle were needle biopsied to obtain tissue samples of less than 6 mg wet weight to assess myocardial metabolism at these precise sites. Epicardial areas of ST segment elevation had marked lactate accumulation and high energy phosphate depletion. Isoelectric sites were areas of either no lactate accumulation or mild lactate accumulation and high energy phosphate concentrations that were greater than those found at site of ST segment elevation. Thus, the data obtained indicate that epicardial sites of ST segment elevation are locations of profound anaerobic metabolism and of both epicardial and endocardial ischemia.
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PMID:Relationship between myocardial metabolism and epicardial ST segment alterations during myocardial ischemia. 118 66

During an atrial pacing test, a correlative study in myocardial lactate, glucose, potassium, and inorganic phosphate balances was done in 34 patients with clinical evidence of ischemic heart disease. Electrocardiogram was continuously monitored while left ventricular end-diastolic pressure (LVEDP) was measured before and immediately after pacing. Coronary angiograms performed after the pacing test revealed atherosclerotic narrowings in all patients. During pacing, 16 patients developed anginal pain, and their LVEDP increased significantly. The other 18 patients had no angina and no significant change in LVEDP. In these 18 patients, there were no significant changes throughout the pacing study in myocardial balances of lactate, glucose, potassium, and inorganic phosphate. In contrast, the 16 patients with induced angina during pacing showed a significant myocardial production of lactate and a loss of potassium. Myocardial inorganic phosphate loss was not statistically significant. There was no significant change in myocardial glucose extraction during angina, although a slight increase was observed during the 1st min afer pacingmthere was no correlation between the arterial concentration and the myocardial extraction of these substances. N stoichiometric relationship was found between glucose and lactate or between potassium and inorganic phospahte balance; Myocardial extraction and production of lactate correlated best with inorganic phosphate uptake and loss. In the preset study, lactate was a more reliable metabolic indicator of myocardial ischemia than potassium and inorganic phosphate, although these last two substances may be helpful in acheiving a greater accuracy for biochemical diagnosis of ischemia. Myocardial glucose balance was of no value as a metabolic indicator of ischemia in this pacing study.
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PMID:Comparison of changes in myocardial balances of lactate, glucose potassium, and inorganic phosphate during pacing-induced angina. 120 74

Isolated perfused working rat hearts were subjected to elective cardiac arrest for 20 or 30 min. Various methods of arrest were studied, either singly or in combination and with or without coronary perfusion. The functional recovery of the heart following the termination of arrest was found to be related to the concentration of ATP and creatine phosphate in the myocardium at the end of the period of arrest. In turn, these concentrations were dependent upon the method used to induce arrest. Normothermic ischemic arrest led to a marked reduction in high energy phosphates and a poor functional recovery. In contrast, coronary perfusion with hypothermic solutions or solutions containing high concentrations of potassium, induced arrest without depleting ATP or creatine phosphate. These procedures conferred considerable protection on the myocardium and thus permitted good recoveries. The energy status and recovery associated with ischemic arrest could be improved by combining the ischemia with hypothermia or potassium arrest. The latter, while increasing recovery significantly, still failed to afford complete protection to the myocardium. Potassium chloride gave greater protection than potassium citrate. When topical hypothermia was combined with ischemia, a time and temperature relationship was demonstrated but effective protection could only be obtained with severe topical hypothermia over a relatively short time period. The results stress the importance of maintaining high energy phosphates during arrest, and this requires the provision of a continuous supply of oxygen and nutrient, which may perhaps be best achieved by ensuring continuous and adequate coronary perfusion.
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PMID:Ischemic damage and metabolism during elective cardiac arrest. 120 80

An improved dog model to study the effect of drugs on myocardial metabolism during ischemia is described. A reproducible degree of ischemia could be obtained by partial occlusion of the anterior descending branch of the left coronary artery (LAD), using an inflatable cuff with a micrometer. The possibility of inducing the stenosis twice in the same animal has the advantage that the animal can be used as its own control. The reproducibility of the degree of ischemia was demonstrated by the nonsignificant differences in local venous lactate, inorganic phosphate, and glucose concentrations after the first and second stenosis. The mean pressure difference over the stenosis was used to express the degree of coronary artery narrowing. In this model, one does not have to rely on the collateral circulation in collecting local venous blood. Moreover, it is very likely that this blood is obtained from the most pronounced ischemic area, which was localized with radioactive microspheres. At this degree of stenosis, left ventricular function was not affected too much, as was demonstrated by the slight changes in dP/dt max, and systolic and diastolic aortic pressure after induction of the stenosis. The usefulness of our model to evaluate the activity of drugs is demonstrated by the effect of fentanyl, a potent morphine-like analgesic, on the poststenotic local venous lactate and inorganic phosphate concentrations.
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PMID:An improved animal model for studying the effect of drugs on myocardial metabolism during ischemia. 120 87

Inhibition of adenine nucleotide translocase by elevated levels of long chain acyl-CoA esters has been shown to occur during the onset of ischemia in experiments conducted on dogs. Other findings indicate that, as a consequence of translocase inhibition, the production of mitochondrial creatine phosphate was abolished and, in this manner, respiration was slowed to state 4 or an ischemic-like condition. A variety of biochemical, hemodynamic, and ultrastructural evidence further suggest that this inhibition of adenine nucleotide transport in and out of the heart mitochondria may be the initial and key disturbance which "triggers" the more drastic metabolic changes known to occur as the degree of ischemia becomes more severe. The mitochondrial "damage" caused by long chain acyl-CoA ester inhibition of adenine nucleotide translocase appears to be reversible by carnitine.
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PMID:Role of adenine nucleotide translocase in metabolic change caused by ischemia. 120 88

After local complete ischemia at normothermia of 60, 100, 140, and 180 min duration the status of the adenylic acid-creatine phosphate system in the canine myocardium recovered to 98, 85, 74, and 30 percent of the control values, whereas glycogen was restored even more. In the infarcted myocardium the extent of alterations of the metabolic status was a function of the residual blood flow. Deviations from a regular metabolic status developed if the blood flow dropped below about 35 ml/min/100 gm. This critical flow rate is expected to vary with the energy requirement of the heart, but it is in keeping with results obtained by Rudolph and coworkers (personal communication) who found that patients with a myocardial blood flow below 30 ml/min/100 gm had a life expectancy of less than 1 month. In the nonaffected myocardium, both in experiments with local complete ischemia and in experiments with infarction, the metabolic status was always within normal ranges. This is in contrast to results published by Gudbjarnason (1971/1972) and Gudbjarnason, Puri, and Mathes (1971), who found that in noninfarcted myocardium tissue levels of ATP and creatine phosphate decreased to about 50 percent of the control values and that there was no restoration to normal values within 10 days after infarction.
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PMID:Effect on myocardial metabolic pattern of local complete and incomplete ischemia. 122 39

The effects of metabolic accumulation on myocardial metabolism during global heart oxygen deprivation were evaluated in a working in situ swine heart preparation with controlled total coronary blood flow. Myocardial oxygen consumption was depressed to a similar extent by either reducing total coronary flow 60 per cent (ischemia, low coronary perfusion) in 10 swine or by decreasing coronary perfusate PO2 to 30 mm. Hg at normal flows (hypoxemia, high coronary perfusion) in 13 swine. Compared with findings in 13 control hearts, ischemia significantly (p less than 0.05) decreased myocardial oxygen consumption (640 to 390 mumole per hour per gram), glucose uptake (185 to 16 mumole per hour per gram), and free fatty acid consumption (32 to 17 mumole per hour per gram). ttissue levels of glycogen, creatine phosphate, and adenosine triphosphate (tatp) were significantly reduced (p less than 0.005), and tissue lactate, adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were increased (p less than 0.001). During hypoxemia, glucose uptake was increased (240 mumole per hour per gram) and free fatty acid consumption was somewhat less depressed (19 mumole per hour per gram). Creatine phosphate and ATP were higher than with ischemia (p less than 0.01), and lactate, ADP, and AMP accumulations were less (p less than 0.01). Thus, in the period immediately following myocardial oxygen deprivation, inadequate coronary perfusion caused greater metabolic buildup which inhibited myocardial substrate utilization and energy production. High coronary perfusion, even though the perfusate was unoxygenated, was associated with greater preservation of substrate utilization, higher levels of high-energy phosphates, less accumulation of metabolic products, and a longer survival. These data suggest a critical role of coronary perfusion in protecting myocardial metabolism in the immediate period following global heart hypoxia.
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PMID:Effects of coronary perfusion during myocardial hypoxia. Comparison of metabolic and hemodynamic events with global ischemia and hypoxemia. 126 57

The effect of ischemia on synthesis of myocardial proteins was investigated using a model of perfusion in which low levels of coronary flow were provided to paced hearts worked against a closed aortic outflow tract. These conditions rapidly produced ischemia and ventricular failure, as evidence by reduced coronary flow, increased left atrial pressure, and decreased pressure development. Protein synthesis was inhibited in a subsequent 1-hour period, during which a minimal coronary flow was maintained by retrograde perfusion. ATP, GTP, and creatinine phosphate were depleted in ischemic hearts and AMP accumulated. Production and accumulation of lactate within the tissue increased, whereas palmitate uptake was inhibited. The inhibition of protein synthesis was not associated with reduced levels of intracellular amino acids. During ischemia, decreased levels of ribosomal subunits as compared to paced or unpaced aerobic hearts suggested that peptide chain elongation was slow relative to initiation. Provision of insulin further reduced subunit levels but did not increase protein synthesis, suggesting that the hormone did not prevent inhibition of peptide chain elongation in energy-poor hearts.
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PMID:Effects of anoxia and ischemia on protein synthesis in perfused rat hearts. 126 87

The Na+/Ca2+ overload inhibitor R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl)-N-methyl-2- benzothiazolamine) has been reported to prevent or attenuate ischemia- as well as ouabain-induced cellular sodium and calcium load. We investigated the potency of this compound in preventing mechanical, biochemical, and ultrastructural consequences of ouabain (OUA) intoxication in isolated rabbit heart. The protective effect of the digitalis antidote phenytoin (PHT) on the consequences of ouabain intoxication was examined for comparison. In isolated perfused rabbit heart, OUA (0.4 microM) caused an increase in left ventricular end-diastolic pressure (LVEDP) that was accompanied by depletion of high-energy phosphates (80% less than in control), accumulation of tissue lactate (12-fold) and damage of contractile elements and mitochondria. Accumulation of lactate was associated with a decrease in oxygen consumption by the isolated perfused heart. R 56865 (1.0 microM) and phenytoin (60 microM) prevented increase in LVEDP, breakdown of the energy-rich phosphates creatine phosphate (CrP) and ATP, accumulation of lactate, and morphologic changes induced by OUA. The above-mentioned toxic effects of OUA are interpreted as consequences of mitochondrial failure finally leading to breakdown of the oxidative phosphorylation. Thus, we conclude that the protective action of both compounds, R56865 and PHT, may be attributed to prevention or attenuation of mitochondrial failure due to OUA-induced disturbance of ion homeostasis.
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PMID:Effects of R 56865 and phenytoin on mechanical, biochemical, and morphologic changes during ouabain intoxication in isolated perfused rabbit heart. 127 87

In the initial seconds after a sudden reduction in coronary blood flow, a temporary mismatch between myocardial energy demand and supply exists. The mechanisms underlying the rapidly ensuing reduction in contractile function in the ischemic myocardium are still unknown. In the presence of some residual blood flow, a state of "perfusion-contraction matching" develops. The metabolic status of such hypoperfused myocardium improves, since myocardial lactate production is attenuated and creatine phosphate (CP), after an initial reduction, returns toward control values. The hypoperfused myocardium responds to inotropic stimulation by dobutamine. The recruitment of an inotropic reserve implies increased energy utilization. During inotropic stimulation, after partial normalization, lactate production is again increased, and CP is decreased again. Thus, a supply-demand imbalance that had been at least partially corrected by the ischemia-induced decrease in regional contractile function is precipitated again. A situation of chronic contractile failure in viable myocardium that normalizes upon reperfusion has been termed myocardial "hibernation." Myocardial "stunning" is characterized by a reversible postischemic contractile dysfunction despite full restoration of blood flow. The details of the underlying mechanisms are not clear. An inadequate energy supply and impaired sympathetic neurotransmission have been excluded. Potential mechanisms, which are not mutually exclusive, may include (a) damage of membranes by free radicals, (b) an increase in free cytosolic calcium during ischemia and reperfusion, and (c) a decrease in the calcium sensitivity of the myofibrils. The equally pronounced increases in regional contractility in normal and "stunned" myocardium during postextrasystolic potentiation and the infusion of calcium or the calcium-sensitizing agent AR-L-57, however, suggest an unchanged calcium sensitivity of reperfused myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of "hibernating" and "stunned" myocardium with focus on the use of calcium antagonists in "stunned" myocardium. 128 10


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