UMLS:C0022116 - FACTA Search

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

Starting from the assumption that tumor cells constantly experience transient ischemia and anoxia, and that this results in metabolic stress which is reflected above all, on the concentration of ATP, ADP and AMP, in other words, the adenine nucleotide pool (AdN), the aim of our research was to study the degradation and resynthesis kinetics of that pool on two types of malignant cells. All experiments were conducted in vitro with cells of the transplantable tumors of Ehrlich's ascitic carcinoma and the AS 30D hepatoma, and metabolite analyses were carried out enzymatically or by way of the HPLC chromatography method. It was found that immediately after the setting on of anoxia, there comes not only to a fall in ATP, but also to a fall in the complete adenine nucleotide pool for about 50%. The further maintenance of anaerobiosis does not have a significant influence on the AdN pool. The adenine nucleotide pool resynthesis is very rapid in the examined cells, and in the presence of glutamine and inosine, there comes to an occurrence of its significant growth. Evidence is given that the resynthesis in Ehrlich's ascitic carcinoma cells is made possible through the purine nucleotide cycle, which probably brings about the intensive glutamine oxidation and aspartate production, while in the AS 30D hepatoma cells it develops by means of adenosine kinase. The AS 30D hepatoma cells maintain a high ATP level in the absence of oxygen for a long time, provided that iodine-acetate is not added, which points to the fact that they have some other kind of energetic reserve aside from ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Kinetics of degradation and resynthesis of the adenine-nucleotide pool in tumor cells]. 209 81

In ischemic canine kidneys protected by Bretschneider's HTK solution the glycolytic lactate production is limited by a low renal substrate content. However, for anaerobic energy supply ischemic organs depend on glycolysis. To evaluate the role of glycolysis in renal protection, the relationship between lactate production and anaerobic energy supply was examined in protected kidneys of dogs, sheep, and swine. Additionally, in canine kidneys an attempt was made to improve anaerobic energy provision by adding glucose to the protective solution. The results were as follows: (1) According to increasing lactate production from swine to dog to sheep, intraischemic ATP decay was delayed least in swine and most in sheep. (2) Glucose addition (10 mM) to the HTK solution roughly doubled the time for ATP to fall to 1 mumol/g dry wt (tATP) in dogs. (3) The greater the lactate production in all three species, the lower the decrease in SAN (ATP + ADP + AMP) from 5 to 120 min of ischemia. (4) A glucose additive in the protective solution led to a significant (p less than .005) increase of SAN in dogs at 120 min of ischemia. A sufficient substrate supply seems to be an essential component of a reliable renal protection.
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PMID:Glucose content and efficiency of glycolysis in protected ischemic kidneys of different species. 212 43

The brain ischemia of spontaneously hypertensive rat was produced gradually by bilateral ligation of the common carotid arteries. The cortical blood flow was measured with a laser doppler flowmeter before and after ligation of the arteries. At the specified intervals, the brain was frozen in situ with liquid nitrogen. The concentration of blood glucose and glycolytic intermediate in frozen brain were measured and the relationship between glycolytic activity and the concentrations of effectors to PFK-1, such as fructose 2,6-bisphosphate, fructose 1,6-bisphosphate, AMP, ATP, Pi and citrate, was investigated. The changes in glycolytic intermediates, pyridine and adenine nucleotides concentration showed that ischemic change occurred in the brain tissue after 30 min of bilateral ligation of the common carotid arteries, in correlation with the decrease in cortical blood flow. The rate of lactate formation increased during the 30-60 min interval and finally decreased during 60-120 min period of ischemia. This indicates that anaerobic glycolysis was accelerated during the early stages of ischemia. The most potent activator of PFK-1, fructose 2, 6-bisphoshate, increased from 5.3 or 6.7 nmol g during the initial stage of ischemia, and this change preceded the activation of glycolysis and the increase in fructose 1,6-bisphosphate concentration, a result indicated that fructose 2,6-bisphosphate does participate in the activation of glycolysis during brain ischemia in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Glycolytic activity and fructose 2, 6-bisphosphate changes in rat brain during ischemia]. 214 15

We studied protective effects of Dibutyryl cyclic AMP (DBcAMP) which is a permeable form of cyclic AMP on ischemic liver failure (ischemic time: 90 minutes). Mongrel dogs were used. A portal-systemic bypass was established by inserting a heparinized catheter between the splenic vein and the femoral vein. Acute liver failure was induced by the en bloc clamp of the porta hepatis. In the treated group, 0.1 mg/kg/min (total dose, 300 mg) of DBcAMP was injected intravenously from three hours before the clamp to the end of the experiment. The control group was injected physiological saline. Effects of DBcAMP were evaluated according to survival rates, blood pressure, serum biochemical findings, hepatic blood flow, ATP levels in liver tissues and histological findings. The survival rates were 16% in the control group, and 88% in the treated group. The mean blood pressure after reperfusion was rapidly decreased in the control group while in the treated group, it was maintained nearly 100 mmHg. Serum biochemical findings, hepatic blood flow and tissue ATP levels were significantly improved in the treated group. On histological findings, necrosis with bleeding was observed one day after ischemia in the control group while in the treated group mild chronic ischemic change without necrosis was observed on two weeks after ischemia. In conclusion, ischemic liver failure was apparently protected by the administration of DBcAMP.
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PMID:[Protective effects of DBcAMP on ischemic liver failure in dogs]. 216 42

Calcium ions are important in many aspects of normal cardiac function as well as in the response to certain pathologic states. The contribution that myocardial calcium influx makes to the cardiac action potential and the pharmacologic efficacy of compounds designated as calcium channel blockers is examined with respect to current knowledge regarding the structure and characteristics of cardiac sarcolemmal calcium channels. Once intracellular, calcium provides the link between cardiac electrical activity and actual mechanical shortening of cardiomyocytes through a complex interaction of regulatory and structural contractile proteins. This is followed by calcium clearance from the cytosol; the mechanisms by which this occurs are manipulated by drugs such as the digitalis glycosides to enhance myocardial contractility. The importance of intracellular 'second messengers' (eg, cyclic AMP) in constituting a final common pathway for the effects of certain cardiotonic agents is defined. The significance of abnormal calcium homeostasis under conditions of heart failure, myocardial infarction, ventricular fibrillation and cardiomyopathy is examined. The role of calcium in the mediation of myocardial damage under conditions of ischemia and secondary to a phenomenon known as 'the calcium paradox' is discussed. The finding that neonatal hearts are more vulnerable to ischemic contracture than adult hearts may be partially explained by differences between neonatal and adult myocardial calcium handling. Understanding of the interactions that exist between the calcium ion and the cardiomyocyte requires a sound knowledge of this essential partnership by both the physiologist and the practising physician.
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PMID:Calcium and the heart: an essential partnership. 217 38

Several 2-amino-3-benzoylthiophenes were found to increase the binding of [3H]N6-cyclohexyladenosine to A1 adenosine receptors in rat brain membranes. Concentration-response curves were bell-shaped, with up to 45% stimulation of binding at 10 microM followed by inhibition at higher concentrations. Because these compounds originated from a series of nonxanthine adenosine antagonists, the inhibition of binding was attributed to the presence of interfering adenosine antagonist activity. The compounds stimulated binding of several A1 agonist ligands but only inhibited binding of the A1 antagonist ligand [3H]8-cyclopentyl-1,3-dipropylxanthine, indicating that enhancement was specific for the agonist conformation of the receptor. The enhancement was also specific for the A1 receptor, because agonist binding to A2 adenosine, M2 muscarinic, alpha 2 adrenergic, and delta opiate receptors showed little or no enhancement. Uncoupling of the A1 receptor from the inhibitory guanine nucleotide-binding protein did not prevent enhancement. The enhancers slowed the dissociation of [3H]N6-cyclohexyladenosine from the A1 receptor, implying an allosteric mechanism of action. The inhibition of forskolin-stimulated cyclic AMP accumulation in FRTL-5 cells was employed as a functional index of A1 receptor activation. The enhancers caused up to 19-fold leftward shifts in the concentration-response curve for N6-cyclopentyladenosine and also caused up to 55% inhibition of cyclic AMP accumulation in the absence of agonist. The binding and functional results are consistent with a model in which the enhancers bind preferentially to the agonist conformation of the A1 receptor, thereby shifting the receptor equilibrium in favor of agonist binding. Adenosine enhancers may be useful for ischemia and other conditions involving local energy deficits. More generally, allosteric enhancers may provide a means for strengthening physiological control circuits in a variety of receptor systems.
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PMID:Allosteric enhancement of adenosine A1 receptor binding and function by 2-amino-3-benzoylthiophenes. 217 10

The objective of the present study was to explore mechanisms responsible for activation of ion conductances in the initial phases of brain ischemia, particularly for the early release of K+ that precedes massive cell depolarization, and rapid downhill fluxes of K+, Na+, Cl-, and Ca2+. As it has been speculated that a K+ conductance can be activated either by an increase in the free cytosolic calcium concentration (Ca2+i) or by a fall in ATP concentration, the question arises whether the early increase in extracellular K+ concentration (K+e) is preceded by a rise in Ca2+i and/or a fall in ATP content. In the present experiments, ischemia was induced in rats by cardiac arrest, the time courses of the rise in K+e and cellular depolarization were determined by microelectrodes, and the tissue was frozen in situ through the exposed dura for measurements of levels of labile metabolites. including adenine nucleotides and cyclic AMP (cAMP), after ischemic periods of 15, 30, 60, and 120 s. Conversion of phosphorylase b to a was assessed, because it depends, among other things, on changes in Ca2+i. The K+e value rose within a few seconds following induction of ischemia, but massive depolarization (which is accompanied by influx of calcium) did not occur until after approximately 65 s. Activation of phosphorylase was observed already after 15 s and before glycogenolysis had begun. At that time, 3',5'-cAMP concentrations were unchanged, and total 5'-AMP concentrations were only moderately increased. The results demonstrate that a K+ conductance is activated at a time when the overall ATP concentration remains at 95% of control values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phosphorylase alpha and labile metabolites during anoxia: correlation to membrane fluxes of K+ and Ca2+. 221 20

We have previously demonstrated that induction of the heat-shock response in rats results in improved recovery of isolated Langendorff-perfused rat hearts subjected to low-flow ischemia followed by reperfusion (Currie et al., 1988). The mechanisms underlying this protective effect of heat-shock are uncertain although the protection was associated with enhanced content of the antioxidant enzyme catalase but not superoxide dismutase or glutathione peroxidase (Currie et al., 1988). Various investigators have suggested the importance of improved energy metabolism in determining recovery following ischemia (Pasque and Wechsler, 1984; Haas et al., 1984; Devous and Lewandowski, 1987). We therefore examined, using a working rat heart model subjected to 10 or 15 min zero flow ischemia whether changes in energy metabolites could account for the protective effect of the heat-shock response. Hearts perfused 24 h after induction of heat-shock failed to demonstrate significant improvement of recovery following 10 min ischemia, however recovery was significantly enhanced in hearts reperfused after 15 min ischemia. Ischemia produced a depression in both ATP and creatine phosphate (CP) content whereas a moderate elevation in ADP and AMP and a marked increase in tissue lactate were evident. These changes were unaffected by prior heat-shock treatment. For both durations of ischemia tissue metabolites were determined during early (5 min) and late (30 min) reperfusion. Although partial recovery in high energy phosphates and a return of ADP, AMP and lactate to near-normal levels were evident, no differences in energy products were observed between hearts from normal or heat-shocked animals, in spite of significantly enhanced recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improved post-ischemic ventricular recovery in the absence of changes in energy metabolism in working rat hearts following heat-shock. 223 33

Isolated rat hearts were used to examine whether reperfusion-induced arrhythmias may be caused by washout of substances accumulating during ischemia. This was achieved by subjecting hearts to 10 min of regional ischemia and rendering them transiently inexcitable during the first 1.5 min of reperfusion. Transient inexcitability was induced by switching to cold solution (4 degrees C) shortly before reperfusion (-1.5 min). In controls (no hypothermia), the incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF) were 83% and 92%, respectively, during the first 1.5 min of reperfusion. Transient hypothermia caused inexcitability and asystole, impaired recovery of coronary flow and abolished VT and VF (all P less than 0.05). On subsequent rewarming to 37 degrees C, coronary flow and sinus rate recovered in all hearts. However, VT and VF occurred in only 58% and 25%, respectively (P less than 0.05). These values were similar to those of new episodes of VT and VF occurring in controls during the equivalent period. Therefore arrhythmias had been abolished during transient hypothermia, not merely delayed. The relative contributions of transient impairment of recovery of coronary flow and transient asystole to the antiarrhythmic effects were examined in a further 10 groups of hearts (n = 12/group) in which reperfusion conditions were transiently manipulated. We utilized combinations of hypothermia, ventricular pacing, acetylcholine (ACh) 55 microM (to cause asystole and impairment of recovery of coronary flow), and right atrial excision and left atrial pacing (to permit bradycardia to be transiently induced during reperfusion by temporarily switching off the pacemaker). The results indicated that transient hypothermia was antiarrhythmic as a result of a reduction of excitability, not because of bradycardia or impairment of recovery of flow. The data support the hypothesis that reperfusion unmasks (disinhibits) latent arrhythmogenic components of ischemia (particularly during the first 1.5 min of reperfusion) and that, by inducing inexcitability, transient hypothermia allows these substances to be washed out without their arrhythmogenic effects being manifested. The identities of the arrhythmogenic and antiarrhythmic substances remain to be determined; we suggest that cyclic AMP and potassium, respectively, are likely candidates.
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PMID:Are reperfusion-induced arrhythmias caused by disinhibition of an arrhythmogenic component of ischemia? 223 48

The effect of diltiazem (d-cis-diltiazem) on the ischemic myocardium was compared with that of l-cis-diltiazem, an optical isomer having less potent calcium channel-blocking action, in the isolated, perfused working rat heart. Ischemia decreased mechanical function and tissue levels of ATP and creatine phosphate, and increased tissue levels of nonesterified fatty acids (NEFA), AMP and lactate. Reperfusion did not restore mechanical function, but restored incompletely the levels of metabolites (except NEFA) that had been altered by ischemia. The ischemia-induced changes in NEFA were prevented by d-cis-diltiazem completely and by l-cis-diltiazem incompletely. Other metabolic changes induced by ischemia were attenuated by d-cis-diltiazem but not by l-cis-diltiazem. In heart pretreated with d-cis- or l-cis-diltiazem, both the mechanical function and the levels of metabolites recovered during reperfusion, the degree of recovery with both drugs being similar. These results indicate that not only d-cis-diltiazem but also l-cis-diltiazem has an anti-ischemic action probably due to inhibition of the tissue NEFA accumulation. These results also suggest that the mechanism of the protective effect of d-cis-diltiazem on the ischemic myocardium is not entirely due to the calcium channel-blocking action. Treatment with low Ca2+ (1.0 mM CaCl2) also attenuated the ischemia-induced changes. The interval between reoxygenation and start of function in the reperfused heart that had been treated with low Ca2+ was significantly longer than that with d-cis- or l-cis-diltiazem. The effect of these isomers to shorten this interval may contribute to their common anti-ischemic action.
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PMID:Both d-cis- and l-cis-diltiazem have anti-ischemic action in the isolated, perfused working rat heart. 224 48

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