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)

An in situ working swine heart preparation is described in which total coronary perfusion was controlled. At normal rates of coronary flow, oxygen, glucose, and fatty acid utilization were stable for at least a 60-min perfusion period. With a 50% reduction in coronary flow, oxygen and glucose consumption were reduced during 30 min of perfusion and fatty acid extraction was lower at the end of 30 min. Glycogen utilization was increased, but tissue levels of creatine phosphate, ATP, and lactate were similar to those in hearts receiving normal flow. With a 60% reduction in coronary flow, uptake of oxygen, glucose, and fatty acids were further decreased. Tissue levels of high-energy phosphates and glycogen were decreased and ADP, AMP, and lactate increased. Mechanical performance progressively deteriorated in these hearts, and ventricular fibrillation developed after about 20 min (19.8 plus or minus 3.0 min). The data indicate that this preparation is suitable for the study of myocardial metabolism during mild and severe ischemia and may be useful for the evaluation of pharmacological interventions designed for the treatment of myocardial ischemia.
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PMID:Metabolic responses to varying restrictions of coronary blood flow in swine. 111 86

Analyses of gastric juice withdrawn 3 hours after the pylorus was ligated and of plasma corticosterone and blood glucose after animals were exposed to rotational stress revealed that gastric secretion was highest in controls, intermediate in stressed rats that developed ulcers, and lowest in stressed rats that did not develop ulcers. Neither high nor low gastric secretion correlated with stress-ulcer formation. When initial mucosal ischemia and secretory inhibition, which occurred in all stressed rats, were considered, those that developed ulcers manifested gastric hypersecretion when compared with those that did not develop ulcers. The pathogenetic significance of gastric hypersecretion in stress-ulcer formation is discussed and correlated with mucosal microvascular changes during stress. Mean plasma corticosterone was highest in stressed rats that developed ulcers, next highest in stressed rats that did not develop ulcers, and lowest in control rats. Compared with normal rats, mean blood glucose was lowest in stressed rats and highest in controls. Hypoglycemic changes were more marked in stressed rats that developed ulcers than in stressed rats that did not develop ulcers.
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PMID:Significance of gastric secretory changes in the pathogenesis of stress ulcers. 113 Mar 69

The extent of cellular metabolic deterioration and its reversibility was studied on human skeletal muscle needle biopsies during operations in bloodless field. The tissue levels of high energy phosphates and glycolytic metabolites were analyzed after various times of tourniquet ischemia and compared to contralateral control extremity levels. In the ischemic extremity the phosphocreatine (CrP) levels decreased by 40% within 30-60 min and after 60-90 min a 60% reduction was found. No significant ATP changes occurred. Lactate levels increased by 225% after 30-60 min and by 300% after 60-90 min. The glucose and G-6-P levels increased slightly and indicated glycogenolysis. The rate of the metabolic changes decreased with ischemia time. In the control leg no significant metabolic changes could be seen. After the release of the tourniquet there was a rapid restoration of the phosphagen content and clearance of lactate in the ischemic leg. Near control levels of these substances were seen already after 5 min. The present results show that clinical tourniquet ischemia of up to 90 min duration produces less pronounced metabolic alterations than those seen in working muscle.
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PMID:Human skeletal muscle energy metabolism during and after complete tourniquet ischemia. 114 14

Adult rhesus monkeys were subjected to complete cerebral ischemia for one hour and subsequent recirculation for up to 24 h. Animals with signs of functional recovery (e.g. spontaneous EEG activity) exhibited a partial replenishment of cellular energy sources (ATP, phosphocreatine) and a progressive normalization of cerebral lactate levels. Glucose and pyruvate concentrations showed a transient increase over control values during the early stages of postischemic recirculation. Monkeys without functional recovery lacked a significant resynthesis of energy-rich compounds; adenine nucleotides continued to decrease and lactate concentrations were higher than in animals subjected to ischemia without recirculation. Cerebral polysome profiles remained unaltered during the ischemic period but in all animals a marked disaggregation of polyribosomes with a concomitant increase in ribosomal subunits occurred after the onset of recirculation. In monkeys with indications of functional recovery these changes were reversible but a normal polysome profile was only observed after 24 h of recirculation. The results obtained indicate a postischemic depression of protein synthesis due to an inhibition of peptide chain initiation. After recirculation of the brain for 3-6 h there was evidence for an induction of enzymes involved in polyamine synthesis (ornithine decarboxylase and S-adenosylmethionine decarboxylase). No changes in the activity of these enzymes were observed at the end of the ischemic period, indicating that during complete cerebral ischemia not only the synthesis but also the catabolism of proteins is inhibited.
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PMID:Resuscitation of the monkey brain after one hour complete ischemia. III. Indications of metabolic recovery. 115 69

The capacity for recovery of the normothermic left ventricular myocardium from a regional complete ischemia (RCI) was investigated using changes in the myocardial metabolic status (ATP, ADP, AMP, creatine phosphate (CrP), free creatine, glycogen, glucose, lactate) and alterations of the morphology as parameters. In dogs, an area of the anterior wall of the left ventricular myocardium was temporarily deprived completely of its blood supply by 5--7 overlapping ligatures extending into the heart cavity. The metabolites of the adenylic acid-CrP system returned to normal tissue levels after 30 and 60 min of RCI within 14 and 35 days of recovery, respectively; restoration averaged 82% after 100 min, 74% after 140 min, and 38% after 180 min of RCI after 5 weeks of recovery. At the same time glycogen amounted to 163% after 100 min, 114% min, and 65% after 180 min of RCI. The biochemical data correlated well with the structural changes in the affected myocardium, especially with the amount of de- and regenerating heart muscle cells. These obviously were functionally defect and were not comparable with normal structured and functioning heart muscle cells.
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PMID:Metabolic and structural recovery of left ventricular canine myocardium from regional complete ischemia. 115 19

The rate of lactic acid (LA) permeation from brain tissue to venous blood and utilization in brain tissue was investigated in 13 isolated dog brains before and after an ischemic period of 3 min. LA concentration in the brain, cerebral blood flow, as well as the arteriovenous differneces of LA, glucose, and O2 were determined. LA concentration in cerebral tissue increased from a control value of 254 +/- 42 to 1,606 +/- 177 mumol/100 g brain tissue in the 2nd min after ischemia (mean values +/- SE). Before ischemia no release of LA was found, whereas in the 2nd min after ischemia LA permeation rate had increased to 25.1 +/- 8.5 mumol/100 g brain tissue per minute (P less than 0.005). Up to the 4th min after ischemia no net LA utilization was observed. Thereafter LA utilization increased rapidly and exceeded the LA permeation rate by a ratio of maximally 10:1 between the 12th and 21st min after ischemia. The O2 equivalent of the cerebral metabolic rate for lactate maximally amounted to 2.82 +/- 0.42 mumol-min-1-g-1 or 181 +/- 28%. LA output may be limited by passage of LA across the brain cell and the blood-brain barrier.
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PMID:Rates of lactic acid permeation and utilization in the isolated dog brain. 116 68

The metabolic states of various tissues of newborn rabbits were studied before and after periods of ischemia of 5-40 min. The contents of substances of the energy distributing adenylic acid-creatine phosphate system as well as glycogen, glucose and lactate were determined and the results are discussed in comparison with the well-known values from ischemic tissues of adult rabbits. The preservation of high energy phosphates as well as the rate of glycolytic energy production during the course of ischemia was quite identical in the myocardium of newborns and adults in contrast to the different ability of newborn and adult rabbits to maintain circulation in anaerobic conditions. In the central nervous system the ATP contents decreased to very low levels within a few minutes in both groups although the glycolytic energy production was rather different. But the larger amounts of adenine nucleotides present in the newborns at any time of ischemia indicate a better chance of postischemic recovery. In the livers and the kidneys of the newborns higher rates of glycolytic energy production led to better preservation of the energy-rich substances while in skeletal muscle and the lung only slight differences occurred between newborns and adults.
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PMID:Metabolic patterns in several tissues of newborn rabbits during ischemia. 118 44

A cerebral ischemia was produced by unilateral ligation of the common carotid artery in the neck of Mongolian gerbils (Meriones unguiculatus), which are frequently characterized by deficiencies in the circulus of Willis. Concentrations of glucose, lactate, pyruvate and glycogen were measured in the hemisphere on the side of occlusion and in the contralateral control hemisphere of animals sacrificed after 5, 15 and 30 min, as well as after 1,3,5 and 9 hrs of carotid clamping. Significant decrease of glucose, and increase in lactate and pyruvate concentration were found in the hemisphere ipsilateral to occlusion; the extent of the changes was proportional to the duration of the ischemia. After an initial fall, an increase in the glycogen content occurred in the later stages of ischemia. Glycogen, glucose, lactate and pyruvate were determined also at 1, 5, 20 hrs and 1 week intervals following release of an occlusion lasting for 1 hr. Return to normal values of glucose and pyruvate was seen at 1 hr after release. The lactate and glycogen levels were significantly raised on the occluded side after 20 hrs release. An increased level of glycogen was observed as long as 1 week after a 1-hr carotid occlusion.
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PMID:Experimental cerebral ischemia in Mongolian gerbils. II. Changes in carbohydrates. 120 98

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

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


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