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

The isolated perfused working rat heart preparation has been used to study the effects of respiratory acidosis on myocardial metabolism and contractilly. Hearts were perfused with 5 mM glucose and 10(-2) U/ml of insulin in order to enhance metabolsim of glucose relative to that of fatty acids. After perfusion with Krebs bicarbonate medium at pH 6.6, hearts rapidly ceased performing external work and peak left ventricular pressure fell by 75% after 5 minutes. Oxygen consumption, rate of ATP generation and overall glycolytic flux also declined rapidly. After about 2 minutes of perfusion, the fall of glycolytic flux showed a partial reversal, which was largely accounted for by increased lactate production, so that glucose oxidation decreased further. The reversal of glycoltic flux could be accounted for by partial release of H+ inhibition of phospho-fructokinase by increased tissue levels of adenosine 5'-diphosphate (ADP), adenosine monophosphate (AMP) and P1 and decreased levels of adenosine triphosphate (ATP) and creatine phosphate. The increased proportion of glucose uptake converted to lactate together with an increase of the tissue lactate/pyruvate ratio could be accounted for by inhibition of the malate-aspartate cycle combined with tissue hypoxia. Lactate accumulated in the tissue as a result of a decreased permeability of the plasma membrane to lactate. Decreased oxygen delivery to the myocardium was caused by secondary constriction of the coronary vessels. In further experiments, the coronary flow was regulated by an external pump which delivered fluid at a controlled rate into the aortic cannula above the coronary arteries, and the degree of tissue hypoxia was monitored by measuring changes of pyridine nucleotide reduction state by surface fluorescence techniques. The effects of acidosis uncomplicated by possible hypoxia were compared directly with those produced by ischemic hypoxia. The effects of acidosis under these conditions were similar to those described above, and to those produced by ischemia. From these and other data it is concluded that the effects of ischemia are caused by a lowering of the intracellular pH, which decreases the rate of energy production relative to the rate of energy demand. However, it is suggested that the primary cause of the decreased peak systolic pressure with either acidosis or ischemia is not a result of a defect of energy metabolism, but is due to alteration of the calcium cycle of the heart. Possible causes of irreversible heart failure after prolonged ischemia are discussed.
 ...
PMID:Contribution of tissue acidosis to ischemic injury in the perfused rat heart. 0 93

The rate of coronary flow reaching the oxygen-linited heart appears to be crucial in determining the myocardial tissue metabolic response. The tissue metabolic response to anoxia, well studied in hearts perfused with anoxic media, differs in many important ways from the response to ischemia. In regional ischemia (developing infarction) there is still a residual oxygen uptake which is reduced approximately to the same extent as the delivery of O2; there is also decreased delivery of substrates and decreased removal of CO2, H+, and lactate, with increased concentrations of these metabolites. Contents of hexose monophosphates rise rather than fall in anoxia. Measurements of glycolytic intermediates show an initial burst of accelerated glycolytic flux lasting less than 1 minute after coronary artery ligation; thereafter rates of flux decrease to control values or even less at 120 minutes. Relative inhibition of phosphofructokinase (PFK) activity may be explained by a slow rate of fall of ATP and a developing intracellular acidosis. In this model, glucose accounts for a greater part of the residual oxidative metabolism than does free fatty acid (FFA).
 ...
PMID:Effects of regional ischemia on metabolism of glucose and fatty acids. Relative rates of aerobic and anaerobic energy production during myocardial infarction and comparison with effects of anoxia. 0 2

The behavior of a model for the partial depletion of adenine nucleotides in the perfused rat heart has been compared for ischemic and high coronary flow anoxic conditions. The accumulation of noradrenaline in the interstitial fluid greatly activates adenylate cyclase ultimately resulting in the degradation of 11.02 micronmol/g dry wt of ATP to adenosine, inosine, and hypoxanthine in 30 min. The high coronary flow rate during anoxic perfusion promotes washout of the noradrenaline from the interstitial fluid so that the hormone accumulates to only one fifth of its highest level in ischemia. This results in only slight activation of adenylate cyclase and in insignificant degradation of ATP in 2 min. The behavior of the model has been examined for two aerobic conditions--a transition from light to heavy work (2 min) and a transition from substrate-free to glucose perfusion (12 min), In both cases adenylate cyclase was not activated above its basal activity, and insignificant depletion of adenine nucleotides is predicted by the model.
 ...
PMID:Computer simulation of ischemic rat heart purine metabolism. II. Model behavior. 1 61

Changes in cerebral cortex concentrations of high-energy phosphates, glycolytic metabolites, citric acid cycle intermediates, associated amino acids, and ammonia, were studied after 5, 15 and 30 min of incomplete ischemia in rats anesthetized with 70% N2O or 150 mg.kg-1 of phenobartibal. Previous results have shown that with this type of ischemia (bilateral carotid artery occlusion combined with reduction in blood pressure to 50 mm Hg) cortical blood flow is reduced to below 10% of nitrous oxide values, whether animals are anesthetized with 70% N2O or 150 mg.kg-1 of phenobarbital. In animals under 70% N2O, changes in tissue concentrations of phosphocreatine, ATP, ADP and AMP were similar to those previously obtained in complete ischemia. However, some glucose remained in the tissue, and the lactate concentrations gradually rose to reach excessive values. Changes occuring in glycolytic and citric acid cycle intermediates were similar to those seen in complete ischemia but, after 30 min, there was some reduction in the pool size of amino acids. In those animals given phenobarbital and which lost all EEG activity during ischemia, changes in cerebral metabolites were virtually identical to those observed in nitrous oxide-anesthetized animals. However, some animals exposed to 5 or 15 min of ischemia had some remaining EEG activity. In these, cerebral energy state was significantly less deranged, and levels of glycogen, glucose and pyruvate were higher.
 ...
PMID:Effects of phenobarbital in cerebral ischemia. Part I: cerebral energy metabolism during pronounced incomplete ischemia. 2 84

Rats with different levels of blood glucose concentration were exposed to 10 min of complete brain ischemia achieved by compression of neck vessels by a pneumatic cuff. All normoglycemic rats survived the ischemic period and made the best clinical recovery. Hyperglycemic rats died within 12 h. Seizure activity was observed in all animals in this group. Three of eight hypoglycemic rats died between 3 and 16 days. The clinical recovery was less complete than in the control group. Thus, recovery from cerebral ischemia depends upon preischemic blood glucose concentration. Hyper- and hypoglycemia hamper the clinical recovery after transient cerebral ischemia.
 ...
PMID:Clinical restitution following cerebral ischemia in hypo-, normo- and hyperglycemic rats. 3 Feb 50

Cerebral ischemia was produced by a combination of vascular occlusion and mild systemic hypotension in 2 groups of rabbits. Arterial blood pressure, arterial pH, arterial blood gases, blood glucose and PCV were monitored and recorded before, during and for 3 hours after reperfusion. Return of EEG activity, vasomotor control, spontaneous ventilation and corneal reflex were also recorded. At 4, 8, 12, 24 and 48 hours after reperfusion, the rabbits' neurologic status was assessed according to an arbitrary scale based on motor function. The 2 groups differed in return of reflexes and motor function. Eighty percent of the rabbits ischemic for 20 minutes and 75% of the rabbits ischemic for 30 minutes survived. The graduated response of motor function to cerebral ischemia is attributed to the ventilatory and circulatory support given the rabbits for the first 3 hours after reperfusion. The graduate response of motor function to ischemia supports the suggestion that motor function can be used as an index of neurologic damage.
 ...
PMID:Survival of rabbits after prolonged cerebral ischemia. 3 15

We measured total and regional cerebral blood flow (CBF, rCBF) and cerebral metabolic rate (CMR) of oxygen (O2), glucose (G), and lactate (L) levels for 4 h after 16 min global brain ischemia in rhesus monkeys with and without post-insult thiopental therapy. Eleven monkeys weighing 4-5 kg anesthetized with 1 percent halothane, 66 percent nitrous oxide and 33 percent oxygen, were subjected to 16 min global brain ischemia by a combination of trimethaphan hypotension (to a mean arterial pressure of 50 torr) and a high pressure (1500 torr) neck tourniquet. Post-ischemia, 7 monkeys were untreated (controls) and 4 received thiopental 90 mg/kg infused intravenously over 60 min, beginning at 5 min post-ischemia. Total CBF and rCBF were measured by continuous monitoring of cerebral venous (torcula) and parietal-occipital (external scintillation) 133Xe activity, respectively, after intra-innominate artery injection of 500 micronCi 133Xe in saline. In control monkeys, hyperemia in rCBF, but not in total CBF was observed at 6-7 min post-ischemia, whereas both total CBF and rCBF increased in thiopental treated monkeys. The hyperemia in thiopental treated monkeys coincided with an increase in CMRG without a proportional increase in CMRO2 or lactate levels. Indeed, CMRO2 was depressed in the first 30 min post-ischemia. At 30 min post-ischemia, CMRO2 rose to twofold greater than pre-ischemia in control monkeys, but only to pre-ischemic levels in thiopental treated monkeys. The data suggest that thiopental therapy improves distribution of brain blood flow and brain glucose uptake early post-ischemia and depresses CMRO2 later post-ischemia.
 ...
PMID:Brain blood flow and metabolism after global ischemia and post-insult thiopental therapy in monkeys. 11 95

In vivo interstitial muscle pressures measured by wick catheter, tissue gas tensions measured by mass spectrometer, and glucose and high-energy phosphate metabolism measured fluorometrically were studied in the anterior tibial (AT) and vastus lateralis (VL) muscles of primate limbs during and following tourniquet ischemia (2.5 hours; 400 mm Hg) to elucidate postischemic edema and its metabolic consequences. During ischemia, interstitial pressure in the VL rose, while in the AT it decreased, but 24 hours later pressures in both experimental muscles were significantly greater than those in the controls. In both experimental muscles PO2 decreased significantly within 15 minutes of ischemia. PCO2 increased significantly in the AT at 30 minutes and at 75 minutes in the VL muscle. Twenty-four hours later only PO2 in the experimental AT was significantly different than its matched control. During ischemia glucose and phosphocreatine (CrP) decreased significantly, and G-6-P and lactate increased significantly in both muscles, but at 24 hours glucose levels were 25% lower and G-6-P 16.2% higher in the experimental AT and CrP 34% lower in the experimental VL. This study shows that there are significant acute and delayed alterations in primate muscle metabolism following tourniquet ischemia and suggests that these changes may be related to the anatomic location of the muscle studied and the type of trauma it has sustained.
 ...
PMID:Effects of tourniquet ischemia and postischemic edema on muscle metabolism. 11 47

Regional ischemia results in infarction even in the presence of residual oxidative metabolism. Although glycolytic flux is relatively inhibited at the level of phosphofructokinase, glucose competes more effectively than does free fatty acid for the residual oxygen supply. Glycogen is not the major energy source until effective collateral flow is virtually zero.
 ...
PMID:Estimated glycolytic flux in infarcting heart. 13 60

The evolution of experimental myocardial infarction in the Rat with or without revascularization has been studied histochemically and histoenzymatically in 56 animals sacrified after 1, 6, 12, 24, 48 hrs and 7 days. Following permanent ischemis (14 animals), there appeared an extended transversal infarction marked by the complete disappearance of all phosphorylase activity (P-ase) after the first hour. During the first 6 hrs, changes appeared in succinodeshydrogenase (SHD) and cytochrome oxydase (Cyt-Ox). Glucose-6-phosphodeshydrogenase (G6PDH) presisted until lysis of the necrotic focus. It was possible to define a perinecrotic marginal area in which Pase activity is absent and SDH is granular "G3 in nature, characterized by continuous remodeling in the first 48 hrs. Following temporary ischemia (42 animals) the evolution was marked by rapid tissue reactions and early regression of the marginal zones. After 48 hrs and 7 days of survival, the planimetric evaluation of the infarcted area shows a definite reduction in the size of the infarctus in 50% of cases following removal of the ligature after 6 hrs, and in 66% of cases following removal of the ligature after 1 hr. It would appear probable that the revitalization of certain myocardial areas may extend from the marginal zones as is suggested by the reappearance in these zones several hrs after revascularization of P-ase and SDH activity. On the other hand, it is also true that the early restoration of blood flow does not always prevent the occurrence of an extended infarction. Certain recent observations have shown microcirculatory changes which are secondary to anoxia and should be studied further.
 ...
PMID:[Histochemical and histoenzymatic study of experimental myocardial infarction in the rat by temporary and permanent ligation of the left coronary artery (author's transl)]. 16 14


1 2 3 4 5 6 7 8 9 10 Next >>