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

Temporary infrarenal clamping of the aorta during reconstructive surgery induces incomplete ischemia of the leg muscle. After release of the clamp, severe muscle metabolic derangement with loss of high-energy phosphate compounds has been observed, indicating a dysfunction or damage of the muscle cells. In six patients operated on for occlusive aortoiliac disease, low-molecular-weight dextran (LMWD) was peroperatively administered for optimal volume loading and prevention of clotting. No heparin was used. Before, during and after the clamping period the central hemodynamics were monitored, and glycogen, glucose, lactate, pyruvate, phosphocreatine (PCr), creatine (Cr), ATP, ADP and AMP content in the thigh muscle were analyzed using enzymatic fluorometric techniques. Even though ischemia developed during the occlusion, no decline in the adenylate (ATP + ADP + AMP) or creatine (PCr + Cr) pools occurred after the clamp was released, and the energy charge of the adenine nucleotides remained unchanged. It is suggested that LMDX prevents rheologic changes impairing the microcirculation during and after the ischemic period, and thereby improves oxygenation of the muscle tissue upon reperfusion.
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PMID:Temporary incomplete ischemia of the legs caused by aortic clamping in man: improvement of skeletal muscle metabolism by low molecular dextran. 616 86

We tested whether cerebral noradrenaline (NA) may play a central role in mediating the increased production of free fatty acids (FFAs) during cerebral ischemia. Levels of FFAs, cyclic AMP, and NA, as well as ATP, ADP, and AMP, were measured in cerebral cortex during decapitation ischemia in rats 2 weeks after unilateral locus ceruleus lesion. Comparisons were made between the results obtained from the contralateral cortex with normal NA content and the NA-depleted ipsilateral cortex. Although NA depletion was associated with a diminished transient rise of cyclic AMP in response to ischemia, it failed to influence the magnitude of FFA increase or the decline of energy state within the 15-min period of ischemia. A more than twofold increase of total FFAs (sum of palmitic, stearic, oleic, arachidonic, and docosahexaenoic acids) was observed in both hemispheres at 1 min after decapitation, when energy failure became manifest. The increased production of FFAs continued throughout the 15 min of ischemia, with a preferential rise in the levels of stearic and arachidonic acids. There was an inverse correlation between FFA levels and total adenylate pool. The results do not support a major role for NA and cyclic AMP in increasing cortical FFAs during complete ischemia. Instead, they are consistent with the view that impaired oxidative phosphorylation activates deacylating enzymes. Disturbance of reacylation due to energy depletion is probably another factor contributing to the continuous increase of FFAs during prolonged ischemia.
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PMID:Free fatty acids and energy metabolites in ischemic cerebral cortex with noradrenaline depletion. 631 5

The transverse guinea pig hippocampal slice preparation was used to model the metabolic changes which occur in vivo during ischemia and recovery. Perfusing brain slices with medium devoid of glucose and oxygen elicits rapid decreases in phosphocreatine, ATP, intracellular pH, and in the evoked field potential recorded in the dentate gyrus. AMP and creatine rise during this period, while ADP and lactate levels remain unchanged. Cyclic AMP exhibits a transient increase in concentration. With the exception of ADP and lactate, these responses are very similar to those observed during in vivo ischemia. The return of glucose and oxygen to the incubation medium reverses these metabolic and electrophysiological effects and also leads to pronounced elevations in cyclic nucleotide concentrations. Metabolite concentrations approach, but do not reach, in vitro steady state levels during the first 30 min of recovery. Total adenylate and creatine steady state levels are approximately 50% of in vivo concentrations. The results suggest that, although hippocampal slices differ metabolically from in vivo tissue, they exhibit a similar pattern of metabolic responses to ischemic and reflow conditions.
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PMID:An in vitro model of ischemia: metabolic and electrical alterations in the hippocampal slice. 632 46

Myocardial recovery during reperfusion following ischemia is critical to patient survival in a broad spectrum of clinical settings. Myocardial functional recovery following ischemia correlates well with recovery of myocardial adenosine triphosphate (ATP). Adenosine triphosphate recovery is uniformly incomplete during reperfusion following moderate ischemic injury and is therefore subject to manipulation by metabolic intervention. By definition ATP recovery is limited either by (1) energy availability and application in the phosphorylation of adenosine monophosphate (AMP) to ATP or (2) availability of AMP for this conversion. Experimental data suggest that substrate energy and the mechanisms required for its application in the creation of high energy phosphate bonds (AMP conversion to ATP) are more than adequate during reperfusion following moderate ischemic injury. Adenosine monophosphate availability, however, is inadequate following ischemia due to loss of diffusable adenine nucleotide purine metabolites. These purine precursors are necessary to fuel adenine nucleotide salvage pathways. Metabolic interventions that enhance AMP recovery rather than those that improve substrate energy availability during reperfusion are therefore recommended. The mechanisms of various metabolic interventions are discussed in this framework along with the rationale for or against their clinical application.
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PMID:Metabolic intervention to affect myocardial recovery following ischemia. 642 32

A new creatine analog, 1-carboxyethyl-2-iminoimidazolidine (homocyclocreatine), has been synthesized and compared with other synthetic analogs of creatine as a substrate for creatine kinase under both in vitro and in vivo conditions. Reactivity with rabbit muscle creatine kinase at 2 mM and pH 7.0 occurred in the order: creatine greater than cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) greater than N-ethylguanidinoacetate greater than N-propylguanidinoacetate greater than guanidinoacetate greater than N-methyl-3-guanidinopropionate greater than 3-guanidinopropionate greater than homocyclocreatine. Homocyclocreatine was 10,000-fold less active than creatine. In the reverse direction at 0.2 mM and pH 7.0: creatine-P greater than N-ethylguanidinoacetate-P greater than cyclocreatine-P much greater than homocyclocreatine-P. Homocyclocreatine-P was 200,000-fold less active than creatine-P. The phosphoryl group transfer potential of homocyclocreatine-P was estimated to be 2 kcal/mol lower than that of creatine-P. Chicks fed 5% homocyclocreatine for 16 days synthesized and accumulated homocyclocreatine-P in breast muscle (32 mumol/g wet wt), leg muscle (24 mumol/g), heart (7 mumol/g), intestine (8.5 mumol/g), and brain (2.4 mumol/g). During ischemia homocyclocreatine-P was utilized by muscle much more slowly for the regeneration of ATP than was creatine-P or cyclocreatine-P. Our results suggest that in tissues of homocyclocreatine-fed animals subjected to a sudden large increase in work load or to ischemia, the residual creatine-P system would rapidly equilibrate with the adenylate system at the new lower cytosolic phosphorylation potential, whereas in the same cytosol the (homocyclocreatine-P)/(homocyclocreatine) ratio would exhibit a hysteresis or memory effect and reflect for a considerable period of time the earlier higher (ATP)/(free ADP) ratio rather than the actual lower (ATP)/(free ADP) ratio.
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PMID:Synthesis and accumulation of an extremely stable high-energy phosphate compound by muscle, heart, and brain of animals fed the creatine analog, 1-carboxyethyl-2-iminoimidazolidine (homocyclocreatine). 682 40

The myocardial energy restoration of ischemic damage by administration of phosphoenolpyruvate during reperfusion was investigated in a paracorporeal heart model modified in the rat. Excised hearts were subjected to 15 min of complete global ischemia at ischemia at 37 degrees C before pulsatile blood reperfusion for 30 min. One group (n = 7) was supplemented with 67 mumol of phosphoenolpyruvate and 0.67 mumol of adenosine triphosphate dissolved in 10 ml of saline and another with plain saline (nonsupplemented) during reperfusion. All hearts were freeze-clamped after 30 min of reperfusion and subjected to energy content analysis. The adenylate charge potential was 0.91 +/- 0.01 (mean +/- SD) for the supplemented and 0.85 +/- 0.06 (mean +/- SD) for the nonsupplemented group. This difference was significant (p less than 0.02). Concomitantly the outflow of creatine kinase was less for the supplemented group. The translocation of phosphoenolpyruvate into the myocardial cells seems possible by blood supplementation of a lower dose of adenosine triphosphate.
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PMID:Myocardial energy restoration of ischemic damage by administration of phosphoenolpyruvate during reperfusion. A study in a paracorporeal rat heart model. 687 18

An ATP-sparing effect has been demonstrated for a number of calcium antagonists. Nifedipine probably has a similar action, but data supporting this view are limited. Therefore we decided to study the effect of nifedipine on high-energy phosphate (and carbohydrate) metabolism in the ischemic rat heart. Langendorff preparations were made ischemic for less than 15 min. The reduction in coronary flow was 60 or 70%. Apex displacement during ischemia, a measure of contractility, was comparable for nifedipine-treated and untreated hearts. Ischemia caused a considerable release of the AMP catabolites adenosine, inosine and (hypo)xanthine, and of lactate. Nifedipine (10-100 micrograms/l) prevented this in a dose-dependent way. The highest dose reduced the release of purines and lactate by 90% (P less than 0.01) and 60% (P less than 0.001), respectively. The drug acted in a similar way during reperfusion. Due to ischemia, the adenylate energy charge (ATP + 0.5 ADP)/(ATP + ADP + AMP), decreased 15% (P less than 0.001); nifedipine at a concentration of 100 micrograms/l prevented this decrease (P less than 0.05). We conclude that nifedipine exerts a beneficial effect on myocardial adenine nucleotide metabolism during ischemia and reperfusion.
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PMID:Nifedipine reduces adenine nucleotide breakdown in ischemic rat heart. 711 72

The purpose of the reported experiments was to measure the concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in the organ of Corti in order to arrive at estimates of three commonly used adenylate ratios. Under normal conditions the concentrations of ATP, ADP, and AMP amounted to 15.8, 3.9, and 0.53 mmoles/kg dry weight, respectively. Of the three substances, AMP is the most sensitive indicator of metabolic stress, since ischemia of 65 seconds leads to an increase of 155%. Under normal conditions the adenylate energy charge, the energy status, and the phosphorylation state amounted to 0.83, 4.1, and 2.5 gram wet weight/mumole, respectively. Within 10 minutes of ischemia the energy charge had declined by 26%, the energy status by 50%, and the phosphorylation state by 76%. The apparent equilibrium constant of adenylate kinase of the organ of Corti was found to be 0.55. The potential significance of these data and their relationship to the situation in the stria vascularis are discussed.
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PMID:Adenine nucleotides of the organ of Corti under metabolic stress. 716 17

The hemodynamic changes which occur when clamping and unclamping the aorta during reconstructive surgery might be a threat to the elderly patient with concomitant cardiac disease. In addition, the cross-clamping induces a temporary ischemia of the legs, with severe metabolic derangement after the release of the aortic clamp. We have studied the effect of a intraoperative adrenergic block (phenoxybenzamine plus metoprolol) on the central circulation and the skeletal metabolism in 14 patients undergoing aortic reconstruction to treat occlusive arteriosclerotic disease. Cardiac output, heart rate, arterial and pulmonary artery pressures, and cardiac filling pressures, as well as femoral venous blood flow were studied. Biopsy specimens of the lateral vastus muscle and blood samples from the radial artery and iliac vein were taken before aortic clamping, and before, 30 minutes, four and 16 hours after the aorta was unclamped, as well as five days postoperatively. In addition, intramuscular temperature and pH were measured. Glycogen, glucose, lactate, pyruvate, ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) contents of the muscle and lactate and pyruvate concentrations in iliac venous and radial arterial blood were determined using enzymatic fluorometric techniques. Mean arterial blood pressure (MAP) averaged 80 mmHg before clamping, chiefly because of the low systemic vascular resistance (SVR), and left ventricular stroke work (LVSW) was normal. At clamping MAP, SVR, LVSW, remained unchanged. MAP and LVSW were unaffected even though SVR decreased slightly after the aorta was unclamped and resulted in an increased cardiac output, mainly due to a higher stroke volume. No major change in the pulmonary circulation was observed. During clamping the muscle lactate/pyruvate ratio increased, intramuscular pH and femoral venous blood flow decreased indicating insufficient tissue perfusion. Energy charge (EC), the adenylate (ATP + ADP + AMP) and creatine (PCr + Cr) pools were, however, unchanged. In spite of a restored blood flow to the legs, a severe metabolic derangement of the muscle was observed after declamping, with lowered EC, ATP + ADP + AMP and PCr + Cr indicating cellular damage. No improvement in the condition of the cells was observed 16 hours after operation. In conclusion, we found that by using neurolept anesthesia and an intraoperative adrenergic block in combination with a differentiated fluid therapy the central circulation stabilized and was largely unaffected by the clamping and unclamping procedures. In spite of the improved central hemodynamics no favorable effect on the skeletal muscle metabolism was observed.
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PMID:Temporary incomplete ischemia of the legs induced by aortic clamping in man: effects on central hemodynamics and skeletal muscle metabolism by adrenergic block. 745 55

Reperfusion after continuous or discontinuous ischemia has a bearing on clinical interventions. An important question is the washout of metabolites after periods of diminished energy state of the myocardial cell. We therefore set out to determine the washout of adenosine and its metabolites after periods of ischemia in an experimental set-up which allowed non-destructive monitoring of the cellular energy state and cytosolic pH over consecutive time intervals. Isolated rat hearts were perfused with hemoglobin-free saline in a nuclear magnetic resonance spectrometer equipped for 31P NMR spectroscopy of phosphorus-containing metabolites, which could be measured over 3-min time blocks. The response of the heart when subjected to 18 min of continuous ischemia and subsequent reperfusion was compared with that when subjected to three 6-min periods of ischemia separated by 3-min periods of reperfusion. The mechanical performance of the hearts, oxygen consumption and efflux of adenosine and its metabolites were measured. The consecutive ischemic periods produced no evidence of preconditioning as judged from the cellular energy state, although the mechanical recovery was better than after continuous ischemia. During the repetitive ischemia/reperfusion protocol the efflux of adenosine was smaller, although the efflux of combined adenylate catabolites did not differ from that after continuous ischemia. The results do not support the view of adenosine being a major effector in the phenomenon of preconditioning.
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PMID:Efflux of adenosine and total adenylate catabolites during alterations of the cellular energy state. An NMR study of continuous and discontinuous ischemia. 757 74


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