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)

Glycerol and mannitol are used clinically as hyperosmolar agents for the treatment of brain edema. In the present study the effects of pre-ischemic treatment with glycerol or mannitol on delayed neuronal death in the gerbil hippocampal CA1 region were examined. In addition, the effects of post-ischemic treatment with glycerol were studied. Male Mongolian gerbils were subjected to transient forebrain ischemia by bilateral common carotid artery occlusion for 5 min. Skull and rectal temperatures were maintained at 36.5 +/- 0.5 degrees C from 30 min prior to occlusion through 60 min post-ischemia. In the pre-treatment study, glycerol (650 mg/kg or 1,300 mg/kg), mannitol (650 mg/kg or 1,300 mg/kg), or saline were administered intraperitoneally to the gerbils 30 min before ischemia. In the post-treatment study, 1,300 mg/kg glycerol was given immediately or 60 min after ischemia. Seven days after the ischemic episode, the brains were fixed and stained for histopathological analysis. Normal pyramidal cell counts per 1 mm length in CA1 (neuronal density, ND) were then assessed under a light microscope. ND in the sham-operated normal control group was 275.3 +/- 16.7 (mean +/- SD). In the pre-treatment study, ND in ischemic gerbils treated with saline was 14.8 +/- 5.0. ND in ischemic animals treated with glycerol (650 or 1,300 mg/kg) or mannitol (650 or 1,300 mg/kg) were 29.0 +/- 15.7, 68.2 +/- 56.7, 88.9 +/- 79.8 and 52.8 +/- 54.4 respectively. Both glycerol and mannitol, at either dose, significantly ameliorated ND. In the post-treatment study, ND in gerbils treated with saline or glycerol immediately after ischemia were 10.3 +/- 3.4 and 43.1 +/- 78.4, respectively, and 60 min after ischemia, 13.1 +/- 9.5 and 68.9 +/- 68.9, respectively. The ND in both post-treatment groups were not ameliorated significantly. These results indicate that pre-treatment with glycerol or mannitol has protective effects on delayed neuronal death in the gerbil hippocampal CA1 region, while post-treatment with glycerol does not produce any significant protection of CA1 neurons from transient ischemia.
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PMID:[Protective effects of glycerol and mannitol on delayed neuronal death in the gerbil hippocampus]. 837 Jul 16

Phospholipid-hydrolyzing activities were examined in rat hearts with ischemia induced by occlusion of the left main coronary artery. When homogenates of ischemic heart were incubated in vitro at 37 degrees C, a significant amount of phosphatidylethanolamine (PE) was degraded, whereas the contents of other phospholipids did not change significantly. During the incubation, a stoichiometrical amount of lysoPE was concomitantly formed. The lysoPE formed had mainly saturated fatty acids and its composition resembled that of fatty acids detected at the sn-1 position in the glycerol backbone of heart PE. No appreciable PE degradation was observed in homogenates prepared from nonischemic rat heart. No difference in phospholipase activities was found between ischemic and nonischemic heart homogenates when exogenous radioactive phospholipids were used as substrates. Rabbit anti-rat 14-kDa type II phospholipase A2 antibody suppressed the degradation of PE observed in ischemic heart homogenates. These findings indicate that the type II phospholipase A2 activity may be involved in the breakdown of endogenous PE in ischemic heart homogenates.
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PMID:Preferential hydrolysis of phosphatidylethanolamine in rat ischemic heart homogenates during in vitro incubation. 840 72

Stressful stimuli such as heat, oxidative stress, heavy metals, and tissue trauma induce the expression of a family of proteins commonly referred to as stress proteins or heat shock proteins. The functions of these proteins are varied but include glycolysis, antioxidant defense, and several postulated "chaperone" functions involving the folding, unfolding, and translocation of other proteins. Heme oxygenase, the enzyme that catalyzes the degradation of heme to biliverdin, is also heat inducible and is, therefore, a heat shock protein. In the kidney, ischemia has been observed by several investigators to induce expression of the more commonly studied heat shock proteins HSP 70 and HSP 72. In addition, exposure of the kidney to myoglobin after glycerol injection induced heme oxygenase. The purpose of this study was to determine whether heme oxygenase is expressed as a stress protein after renal ischemia. Renal ischemia was induced in rats after right nephrectomy by clamping the renal artery for 40 minutes. Gene expression was evaluated after 60 minutes to 96 hours of postischemic reperfusion. There was essentially no expression of heme oxygenase at any of the time points evaluated. The absence of heme oxygenase expression was in striking contrast to the prompt and dramatic expression of HSP 70. This finding is consistent with the concept that all "stress proteins" are not equivalent and that, although there is considerable overlap between heat-sensitive gene promoters and oxidant stress-sensitive gene promoters, there is specificity for the type of stimulus that is able to activate any given stress protein gene.
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PMID:Heme oxygenase is not expressed as a stress protein after renal ischemia. 840 10

To investigate the effect of lactate, pyruvate, and glucose on the endogenous levels of lipids in the normoxic, ischemic, and reperfused myocardium, isolated working rat hearts were exposed to various grades of ischemic insult (15, 30, or 45 minutes). Glucose was present as the basal substrate in the perfusion medium, and lactate (5 mM) or pyruvate (5 mM) was added as the cosubstrate. Lipid metabolism was evaluated by fatty acid accumulation, triacylglycerol turnover, and phospholipid homeostasis. Exogenous lactate significantly increased fatty acid content above preischemic levels after 45 minutes of ischemia. In glucose-perfused hearts, fatty acid levels were even slightly higher than in lactate-perfused hearts, whereas pyruvate-perfused hearts demonstrated less accumulation of fatty acids. By reperfusion, fatty acid levels in glucose-perfused hearts returned to control values. In lactate- and pyruvate-perfused hearts, fatty acid accumulation was further enhanced by reperfusion. When the fatty acid content exceeded 400 nmol/g dry wt during reperfusion, hemodynamic function was impaired, whereas fatty acid levels below 400 nmol/g dry wt did not correlate with hemodynamic recovery. The total triacylglycerol content did not change during ischemia and reperfusion. However, accumulation of glycerol was remarkable during the first 15 minutes of ischemia in all hearts, and release of glycerol by reperfusion was considerable in lactate-perfused hearts after 30 minutes of ischemia and in all groups of hearts after 45 minutes of ischemia. Release of glycerol in association with maintained levels of triacylglycerols suggests turnover of the triacylglycerol pool. The rate of triacylglycerol cycling correlated poorly with hemodynamic recovery. Accumulation of arachidonic acid revealed disturbances in phospholipid turnover. Arachidonic acid accumulation during reperfusion demonstrated a strong relation with impairment of cardiac function. Hence, derangements in phospholipid homeostasis during reperfusion might be involved in myocardial damage, which is influenced by the substrates available.
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PMID:Substrate-induced changes in the lipid content of ischemic and reperfused myocardium. Its relation to hemodynamic recovery. 841 40

Trilinolein, a triacylglycerol with linoleic acid as the only fatty acid residue in all esterified positions of glycerol, was previously found to improve erythrocyte deformability in vitro. In this study, the in vivo antiarrhythmic and anti-ischemic effects of trilinolein in coronary ligated rats were investigated. Male Sprague-Dawley rats were anaesthetized with urethane. Trilinolein, at dosages ranging from 10(-11) to 10(-7) g/kg, was administered intravenously 15 min before ligation of coronary artery. Also, the effect of trilinolein on arrhythmia was studied by ligating the coronary artery for 30 min, then reperfusing myocardium for 10 min. During the 30-min ischemia, trilinolein reduced not only the number of ectopic beats but also the incidence rate and duration of ventricular tachycardia. At 10(-7) g/kg, trilinolein completely suppressed all ventricular arrhythmias. Ventricular arrhythmias during 10 min reperfusion were also reduced by trilinolein at similar dosages. Furthermore, the effect of trilinolein on infarct size was evaluated by occluding the coronary artery for 4 h before the infarct zone was stained and weighed. In rats subjected to 4 h coronary ligation, pretreatment with 10(-7) g/kg trilinolein at 15 min prior to the coronary ligation significantly reduced infarct size. Trilinolein may protect myocardium against ischemic injury and suppress arrhythmia during ischemia and reperfusion.
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PMID:Trilinolein reduces infarct size and suppresses ventricular arrhythmias in rats subjected to coronary ligation. 858 72

Although accounting for 2% of body weight, brain has one of the greatest metabolic rates compared with other organs and systems. The energy metabolic consum is expended mainly in the maintenance of ionic gradient, essential to neuronal activity. Brain receives energy substrates from circulation, with interference of blood brain barrier (BBB). Glucose is the main substrate and has a metabolic rate so high as 150 g/day (0.7 mM/G/min). At cellular level, metabolism of glucose seems to be controlled by phosphofructokynase. If the cellular level were high enough, manose and other products like fructose 1,6 biphosphate, pyruvate, lactate and acetate can be used in the place of glucose. Lactate, when oxyded, consums at least 21% of the cerebral needs of O2. In ischemia and inflammatory infections, brain tissue produces lactate instead of use it. Ketone bodies reduce cerebral needs of glucose; in view of the disturbances that occur in cerebral production of succinyl CoA and guanosine 3 phosphate (GTP), they must be considered as complementary substrate but not as an alternative one. Although they can be metabolized, there are no evidences that brain could produce energy from systemic free fatty acids, even when hypoglicemia is present. Ethanol and glycerol are considered only at experimental level. Brain uptake of aminoacids occur better for long chain aminoacids, specially valine. The aminoacids that are synthetised in the brain (aspartate, gluconate and alanine) show the lower absortion rates. All aminoacids should be oxided to CO2 and H2O. Even when glucose consum is reduced to 30%, aminoacid accounts for only 10% of the energetic expenditure of the brain. To maintain cerebral glucose and oxygen supply to the brain, blood flow must be at least 800 ml/min. The regulation of supply and consumption of energy substrate by the brain is changed in few situations. Among them, are included the oxidation of lactate immediately before milk diet early in development and utilization of ketone bodies at the beginning of lactation. This review includes a brief discussion about the relevance of glucose as the main energy substrate for cerebral tissue in different ages and ischemia or hypoxia.
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PMID:[Control of supply and use of energy substrates in the encephalon]. 858 33

alpha-adrenergic stimulation of patients with ischemic heart disease should intuitively impose a destructive stress. However, therapeutic alpha1-adrenergic receptor mediated cardioadaptation prior to myocardial ischemia protects ventricular mechanical function, promotes electrophysiologic stability, and preserves myocyte viability. Prior to an anticipated cardiac ischemic insult, alpha1-adrenergic preconditioning attenuates ischemic myocardial acidosis by a protein kinase C-(PKC) dependent mechanism. The alpha1-adrenoceptor can directly stimulate calcium-independent nPKC isoforms via diacylglycerol (DAG) or indirectly stimulate calcium-dependent cPKC isoforms through the release of intracellular calcium via inositol triphosphate, (IP3). We hypothesized that alpha1-adrenergic limitation of ischemic acidosis is mediated by the family of calcium-dependent PKC isoforms. [31P]NMR spectra were obtained in isolated, buffer perfused rat hearts treated with alpha1-adrenergic stimulation [phenylephrine (PE) 50 microM, 2 min]; PKC blockade [chelerythrine chloride, (Chel) 20 microM]; or stearoyl-arachidonoyl glycerol (SAG, a DAG analogue, 100 microM, 2 min) administered 10 min prior to ischemia. Control hearts were perfused under normoxic conditions for 20 min. All hearts were then subjected to global ischemia (20 min, 37.5 degrees C). Developed pressure (DP) and heart rate were recorded continuously. pHi was obtained from chemical shift of inorganic phosphate. Immunohistochemical staining was utilized to delineate the translocation and activation profiles of specific PKC profiles established with each stimulus. Pre-ischemic alpha1-adrenergic stimulation did attenuate the myocellular hydrogen ion accumulation during sustained normothermic ischemia (6.90 +/- 0.13 vs control 6.54 +/- 0.10; P < 0.05). General PKC inhibition abrogated this effect (end-ischemic pH 6.17 +/- 0.10; P < 0.05 vs control and PE). Ischemic acidosis was not attenuated following selective nPKC stimulation (SAG, 6.48 +/- 0.08; NS vs control). Myocellular immunohistochemical staining revealed translocation of the calcium-independent PKC-epsilon isoform in the calcium-dependent PKC (SAG) group, but not in response to alpha1-adrenergic stimulation. The results suggest that (1) alpha1-adrenoceptor stimulation limits ischemic acidosis, (2) alpha1-adrenergic stimulated attenuation of ischemic acidosis is PKC dependent, (3) direct nPKC stimulation with SAG does not limit ischemic acidosis, and (4) SAG stimulates nPKC-epsilon isoform activation where alpha1-adrenergic stimulation does not. We conclude that alpha1-adrenergic stimulation limits ischemic acidosis by a cPKC-dependent mechanism and that the mobilization of the IP3 arm by receptor stimuli suppresses PKC-epsilon thus permitting the limitation of ischemic acidosis.
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PMID:Alpha-adrenergic preservation of myocardial pH during ischemia is PKC isoform dependent. 866 Dec 19

Succinyl-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide (Suc-LLVY-MCA) hydrolyzing activities of the 20S and 26S proteasomes in the gerbil cortex following transient forebrain ischemia were examined. Using extraction solutions without ATP, only 20S proteasome activity was noted after separation with glycerol gradient centrifugation. When these extracts were incubated with ATP and an ATP-regenerating system prior to glycerol gradient separation, both 20S and 26S proteasome activities were detected. Following 10 min of ischemia, the activity of the 26S proteasomes decreased, whereas the 20S proteasome activity increased after 30 min of reperfusion. These changes returned to the control level after 1 h. The active 26S proteasomes were formed with ATP-dependent association with the 20S proteasomes and several subunits and the 26S proteasomes degraded ubiquitin-protein conjugates. These results indicate that proteasome activity might not be irreversibly impaired after transient ischemia. However, transient inhibition of ATP-dependent conversion of 20S to 26S proteasomes in vitro must be one of the causes of the accumulation of the ubiquitin-protein conjugates in the early reperfusion period.
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PMID:Changes in proteasome activity following transient ischemia. 871 10

Ischemic preconditioning (PC) has been shown to attenuate intracellular acidification during a subsequent period of ischemia, to minimize stunning, and to decrease infarct size, PKC activation has been suggested to be involved in this phenomenon. The present study is designed to test whether PKC activation could mimic and PKC inhibition could block the PC effects on intracellular acidification during ischemia and on stunning during reflow in Langendorff perfused rat hearts. Prior to 20 min of sustained global normothermic ischemia, groups of hearts were treated with the PKC activators 4 beta-phorbol 12-myristate 13-acetate (PMA) or 1,2-dioctanoyl-srt-glycerol (DOG), a group of hearts was treated with the PKC inhibitor chelerythrine (CH), a group was treated with DOG plus CH, a group was preconditioned with four cycles of 5 min of ischemia and 5 min of reflow, and a group was treated with CH during PC. Recovery of left ventricular developed pressure (% of initial, pretreatment, preischemic LVDP), measured after 20 min of reflow, was improved in hearts treated with DOG, but not PMA (80 +/- 3% (DOG), 55 +/- 3% (PMA) v 51 +/- 3% (control), P < 0.05 between DOG and control), although both caused a similar degree of PKC translocation (measured by fractionation followed by an assay of PKC activity using incorporation of 32P into histone). The improved recovery of LVDP in the PC group and in the DOG group was blocked by chelerythrine. Measurement of pH (by 31P NMR) showed that DOG reduced acidification at 15-20 min of ischemia, although the effect was not as great as PC, while PMA did not reduce acidification. The effect of DOG on pHi was attenuated by CH; however, the PC-induced attenuation of the fall in pHi, was not affected by CH. High energy phosphates (measured by 31P NMR) were not significantly different between any of the groups during ischemia or reflow. This study confirms that the protective effect of ischemic preconditioning on stunning in rat heart can be eliminated by inhibition of PKC, but suggests that the effect of PC on the fall in pHi during sustained ischemia is not mediated by PKC.
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PMID:Effect of ischemic preconditioning and PKC activation on acidification during ischemia in rat heart. 876 27

Changes in creatine compounds, especially the creatine phosphate to creatine ratio (CrP/Cr), are more sensitive indicators than changes in other metabolites for early ischemia in the different muscular tissues of heart, small intestine, skeletal muscle, and aorta. Changes in adenine nucleotide ratios are buffered by CrP reserves and the absolute concentration of adenine nucleotides can vary greatly between different muscular tissues. Accumulation of lactate is indicative of ischemia, but is not as sensitive as the ratio of CrP/Cr, but may better indicate the duration of ischemia. Glycerol also accumulates in muscular tissues during prolonged ischemia, so that consideration of both lactate and glycerol levels together, might confer a better estimate of the duration of ischemia of different muscular tissues.
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PMID:Creatine phosphate as the preferred early indicator of ischemia in muscular tissues. 876 71


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