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)

Dog kidneys were subjected to one, two, or three hours' normothermic ischemia in situ and were then excised for biochemical and histological evaluation. The uptake of para-aminohippurate (PAH) by cortical slices progressively decreased with prolongation of the ischemia, but active transport was never abolished. Glycine uptake and oxygen consumption were only reduced to a modest extent by the ischemia. The intracellular ion levels were drastically altered, with loss of potassium and gain of sodium and chloride, and considerable increases in tissue water were observed. Acid phosphatase was liberated by the whole organ into the venous blood and by the incubated slices into the incubation medium, but both biochemical and histochemical techniques showed that the total quantity of the enzyme in the cells was hardly changed. The histochemical reaction product was localized exclusively in the lysosomes. Morphological damage was slight after one or two hours' ischemia, but more pronounced after three hours, when some cells were seen to be detached from the basement membrane. These relatively minor changes seem insufficient to predict the ultimate fate of the organ after ischemia.
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PMID:Alterations in the dog renal tubular epithelium during normothermic ischemia. 84 66

After the middle cerebral artery of rats was occluded, changes in the content of 14 free amino acids and the activity of antioxidant enzymes in the ischemic striatum were assessed with respect to the duration of ischemia. Glu and Asp levels were significantly reduced by 60 min of ischemia, GABA was increased by 30 and 60 min and Ala was increased by 5, 15, and 30 min. During ischemia, the levels of striatal Gln, Asn, Ser, Tau, Gly and Pro were found to be normal. In comparison with the sham-operated rats, the changes in the content of Thr, His, Arg and Tyr were inconclusive, since the effect of operative stress could not be ruled out on such occasion. Concomitantly, the Zn-Cu superoxide dismutase and glutathione peroxidase activity were significantly reduced by 30 min of ischemia. It revealed that the reduced capacity to scavenge the oxygen free radicals occurred during the early stage of cerebral ischemia. The above changes of Glu, Gln, GABA and Pro level might be considered as the final outcome of the decrease of glutamate synthesis, the acceleration of its conversion to GABA, and the extracellular leakage of glutamate. According to our data, the oxygen free radicals might be involved in the evolution of primary neuronal damage at the ischemic striatum.
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PMID:[Mechanism of neuronal damage caused by cerebral ischemia]. 133 25

We investigated the ability of N6-cyclohexyladenosine (CHA), a potent and selective agonist of the adenosine A1 receptor, to attenuate elevations of levels of extracellular hippocampal glutamate and glycine that result from episodes of transient global cerebral ischemia (TGCI). A total of 30 New Zealand white rabbits were randomly assigned to receive 0 (n = 5), 0.1 (n = 8), 1.0 (n = 6), 10 (n = 6), or 100 (n = 5) microM CHA. The drug was dissolved in artificial CSF (vehicle) and administered via a microdialysis probe placed stereotactically into the dorsal hippocampus. A second microdialysis probe placed into the contralateral hippocampus of each animal was perfused with vehicle alone. Ten minutes of TGCI was induced by neck tourniquet inflation and deliberate hypotension from 0 to 10 min. Microdialysis samples were collected as follows: every 20 min preischemia (at -80, -60, -40, -20, and 0 min); every 5 min during ischemia and in the immediate reperfusion period (at 5, 10, 15, and 20 min); and every 20 min for the remainder of the reperfusion period (at 40, 60, and 80 min). Samples were then analyzed for their concentration of glutamate and glycine by HPLC. Following 10 min of ischemia, glutamate levels increased to a peak of 3.28 +/- 0.55 times baseline and returned to preischemic levels by 40 min, i.e., during reperfusion. Glycine concentrations increased to 5.41 +/- 0.91 times over baseline and remained elevated for the duration of the study.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of cyclohexyladenosine on the periischemic increases of hippocampal glutamate and glycine in the rabbit. 135 2

Glycine preserves tubular cell integrity under hypoxic and toxic conditions in vitro. It also ameliorates cisplatin nephrotoxicity in vivo. We studied the effect of glycine on tubular necrosis from ischemia reflow and on inner stripe injury in an animal model of radiocontrast nephropathy. In all experiments, glycine (75 mg/100 g/h) increased tubular damage in the inner stripe. In the model of radiocontrast nephropathy, the percentage of medullary thick ascending limb (mTAL) necrosis at 24 hours increased from 22% +/- 6% to 41% +/- 9% or 55% +/- 7% with glycine infusion of 75 or 135 minutes, respectively (mean +/- SE, P less than 0.05, analysis of variance [ANOVA]). Renal function was not significantly affected. In rat kidneys subjected to ischemia reflow, mTAL injury following glycine increased from 1% +/- 0% to 12% +/- 6% (P less than 0.05) and from 8% +/- 5% to 49% +/- 8% (P less than 0.01) 24 hours after 30 minutes and 45 minutes ischemia, respectively. Tubular injury in the inner stripe was maximal in the deep interbundle zone, typical of hypoxic, rather than reperfusion, injury. Prior uninephrectomy increased inner stripe damage, but protected the proximal tubules. Both uninephrectomy and glycine infusion were found to contribute to mTAL necrosis. The infusion of glycine for 1 hour in intact rats increased renal blood flow by 44% and tripled urine volume (P less than 0.01). A parallel increase in glomerular filtration rate GFR; by 22% over 90 minutes) fell short of statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of glycine and hypertrophy on renal outer medullary hypoxic injury in ischemia reflow and contrast nephropathy. 159 7

The effects of systemic hypothermia (33.5 degrees C) on the ischemia-evoked release of the neurotransmitter amino acids, glutamate, aspartate, gamma-amino-butyric acid (GABA) and glycine into rat cerebral cortical superfusates were evaluated in the rat four vessel occlusion model. Glutamate, aspartate and GABA, but not glycine, levels were enhanced during and following a 20 min period of ischemia. However, when compared with normothermic ischemic animals, no reductions in glutamate, aspartate or GABA levels in the superfusates were apparent either prior to, during or following forebrain ischemic episodes. Indeed, the superfusate levels of aspartate and GABA were transiently increased immediately following ischemia. Glycine levels were significantly depressed, both pre- and post-ischemia, in cortical superfusates from hypothermic animals in comparison with normothermic rats.
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PMID:The effects of hypothermia on amino acid neurotransmitter release from the cerebral cortex. 167 60

We have previously demonstrated that elevated intraischemic glutamate levels are insufficient, of themselves, to engender ischemic damage. Glycine and gamma-aminobutyric acid (GABA), which modulate glutamatergic activity, may also play a significant role. We compared ischemia-induced changes in glutamate, glycine, and GABA release in a selectively vulnerable region (dorsolateral striatum) to the changes occurring in a region, although rendered ischemic, is usually spared with 20 min ischemia (anterior thalamus). Regional extracellular neurotransmitter levels were measured by microdialysis before, during, and after 20 min of global ischemia induced by 2-vessel occlusion plus systemic hypotension in the rat (n = 5). Similar ischemia-induced increases in glutamate, GABA, and glycine were observed in both striatum and thalamus (19-25 fold, 43-52 fold, and 3-4 fold, respectively). During recirculation, both glutamate and GABA returned to baseline in both regions by 30 min of reperfusion. Glycine levels remained two-fold higher than baseline in the striatum but fell to baseline in the thalamus. To derive a quantitative descriptor reflecting the composite magnitude of aminoacid neurotransmitter changes with ischemia, we defined the 'excitotoxic index' as: [glutamate] x [glycine]/[GABA]. While increases in the excitotoxic index during ischemia were similar for striatum and thalamus, a marked and highly significant increase was found in the striatum compared to the thalamus at early (1 h = 91.5 +/- 27.4 and 25.1 +/- 6.3, P less than 0.01, ANOVA) as well as later recirculation times (2 h = 111.3 +/- 30.9 and 20.9 +/- 3.6, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Excitotoxic index--a biochemical marker of selective vulnerability. 167 23

Cardiac opioid receptors have been shown to be involved in the genesis of arrhythmias during ischemia and reperfusion. The present study was aimed at elucidating the receptor subtype(s) involved in arrhythmogenesis. Two series of experiments were conducted. In the first, effects of prototype opioid agonists, namely, (D-Ala2, NMe4, Gly-ol)-Enkephalin (DAGO), U50,488H and (D-Pen2, Pen5)-Enkephalin (DPDPE) and (D-Ala2, D-Leu2)-Enkephalin (DADLE), representing mu-, kappa- and delta-agonists, respectively, in disturbing the normal cardiac rhythm in the isolated perfused rat heart were investigated. Both DAGO and U50,488H were arrhythmogenic, whereas the effects of the delta-agonists, DPDPE and DADLE at a same dose range (44-396 nmol/heart) as that of DAGO were almost negligible. U50,488H was by far the most potent as it induced ventricular arrhythmias including frequent PVC and VT even at a dose (44 nmol/heart) at which other agonists either produced no or negligible effect. In the second series of experiments, the antiarrhythmogenic effects of mu-antagonist (naloxone) and kappa-antagonist (MR 2266) against arrhythmias arising during ischemia and reperfusion were compared. The effects of MR 2266 were significantly greater than that of naloxone. Results of the present study suggest that the cardiac kappa-receptors are the most likely receptor-subtype involved in arrhythmogenesis during ischemia and reperfusion.
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PMID:Effects of drugs interacting with opioid receptors during normal perfusion or ischemia and reperfusion in the isolated rat heart--an attempt to identify cardiac opioid receptor subtype(s) involved in arrhythmogenesis. 196 62

We evaluated whether regional differences in the magnitude of glutamate, gamma-aminobutyric acid (GABA), and glycine release could explain why some regions are vulnerable to ischemia whereas others are spared. By means of the microdialysis technique, the temporal profile of ischemia-induced changes in extracellular levels of glutamate, GABA, and glycine was compared in regions that demonstrate differing susceptibilities to a 10- and 20-min ischemic insult (dorsal hippocampus, anterior thalamus, somatosensory cortex, and dorsolateral striatum). The degree of ischemia (as established by local cerebral blood flow reduction) and the magnitude of histopathological neuronal damage were also evaluated in these regions. The blood flow reduction was severe and uniform in all regions; however, the histopathological outcome illustrated a different pattern. Whereas the CA1 sector of the hippocampus was severely damaged, the thalamus and cortex were relatively spared from both 10 and 20 min of ischemia. Striatal neurons were resistant to a 10-min insult but severely damaged after 20 min of ischemia. Ischemia-induced increase in glutamate and GABA content were of a similar magnitude and temporal profile in all four brain regions. A uniform increase in extracellular glycine levels was also observed in all four brain structures. The postischemic response, however, was different. Glycine levels remained twofold higher than baseline in the hippocampus but fell to baseline in the cortex and thalamus after both 10- and 20-min insults. In the striatum, glycine levels returned to baseline after 10 min of ischemia but remained relatively high after a 20-min insult.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effect of transient global ischemia on extracellular levels of glutamate, glycine, and gamma-aminobutyric acid in vulnerable and nonvulnerable brain regions in the rat. 207 98

This study examined the effect of preexisting hyperglycemia on the extracellular concentrations of glutamate and glycine in the rabbit hippocampus using in vivo microdialysis during brief episodes of transient global ischemia. Hyperglycemia has repeatedly been shown to exacerbate the neurologic injury produced by episodes of global cerebral ischemia. Under hypoxic conditions, glucose may be metabolized to glutamate, a known neurotoxin which has been implicated as a mediator of ischemic neuronal cell death. In this study, microdialysis probes were stereotactically inserted into the dorsal hippocampus of anesthetized rabbits. Animals were randomized to receive an i.v. infusion of either saline or dextrose. Global cerebral ischemia was then produced by the combination of neck tourniquet inflation and the induction of systemic hypotension. Administration of dextrose had no effect on these basal levels of glutamate or glycine. During ischemia, glutamate and glycine concentrations increased several-fold when compared with baseline. However, hippocampal glutamate concentrations were lower in the dextrose-treated groups during the peri-ischemic period (P = 0.02). Glycine concentrations were higher during the reperfusion period in the dextrose-treated animals when compared with saline controls (P = 0.03). The increased concentration of extracellular glycine which was observed in the dextrose-treated animals may contribute to the neurologic injury which occurs during episodes of global ischemia. The results of this study suggest that hyperglycemia does not exert its detrimental effects by increasing the extracellular concentration of glutamate.
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PMID:Effect of hyperglycemia on peri-ischemic neurotransmitter levels in the rabbit hippocampus. 791 89

L-type Ca2+ channel blockers (CCBs) have been shown to be protective against ischemia-induced injury of the kidney, suggesting that increased intracellular Ca2+ levels ([Ca2+]i) play an important role in the pathogenesis of ischemic cell injury. To assess the role of [Ca2+]i in anoxic injury of the proximal tubule (PT) and the protective effect of CCBs, digital imaging fluorescence microscopy was used to monitor [Ca2+]i in individual PT cells during 60 minutes of anoxia. [Ca2+]i started to rise within 10 minutes and reached maximal levels between 30 to 45 minutes of anoxia. The onset of this increase and the maximal levels reached varied markedly among individual cells. The mean values for initial and maximal anoxic [Ca2+]i were 109 +/- 2 (N = 209) and 422 +/- 14 (N = 240) nM, respectively. Methoxyverapamil (D600; 1 microM) significantly reduced anoxic [Ca2+]i to 122 +/- 5 nM (P < 0.05; N = 79). Removal of extracellular Ca2+ completely abolished anoxia-induced increases in [Ca2+]i, confirming that these increases in [Ca2+]i result from Ca2+ influx. During 60 minutes of anoxia, PT cells showed a gradual decrease in cell viability to 54 +/- 2%. D600 (1 microM) significantly increased cell viability to 64 +/- 3% (P < 0.05). Glycine (5 mM), however, increased cell viability to 77 +/- 4% without a significant reduction in anoxic [Ca2+]i levels. Low Ca2+ medium only protected when 0.1 mM La3+ was included, a condition which increased cell viability to 82 +/- 5%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of Ca2+ channel blockers, low Ca2+ medium and glycine on cell Ca2+ and injury in anoxic rabbit proximal tubules. 793 41


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