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)

The ability of BM-13505, 4-[2-(4-chlorobenzenesulfonylamino) ethyl]-benzene acetic acid), a specific thromboxane/endoperoxide receptor antagonist, to protect the myocardium against ischemia and reperfusion injury, was assessed in an anesthetized cat model. Cats were rendered ischemic by left anterior descending (LAD) coronary artery ligation for 1 1/2 hours followed by reperfusion for 4 1/2 hours. BM-13505 or its vehicle (i.e., Na2CO3) was administered intravenously 30 minutes before reperfusion at a rate of 1 mg/kg followed by 1 mg/kg/hr. BM-13505 significantly (p less than 0.001) reduced the area of ischemic tissue as a percent of total left ventricular mass and total area at risk, without altering basic hemodynamics (i.e., arterial blood pressure, heart rate, or their product) and thereby not influencing myocardial oxygen demand. The mechanism of the protective effect of the thromboxane receptor antagonist appears to be cytoprotective but may involve the prevention of neutrophil-induced cellular damage.
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PMID:Protective effect of the specific thromboxane receptor antagonist, BM-13505, in reperfusion injury following acute myocardial ischemia in cats. 292 97

The activity of three forms of ATPase were examined in fractions of the brain of the gerbil treated with ethylene glycol-N-N-tetra-acetic acid (EGTA) under a variety of conditions of primary and secondary (reflow) ischemia. In animals which were unilateral ischemic (ligation of the right common carotid), damage to Na+, K+-ATPase alone was observed only after at least 6 hr of ischemia had elapsed. The phenomenon occurred in only symptomatic gerbils and was absent in animals which were either asymptomatic or only displayed partial neurological symptoms. Under conditions of bilateral cerebral ischemia, in which both carotid arteries were clamped, only irreversible ischemia (60 min) followed by reflow, was associated with highly significant damage to cerebral Na+, K+-ATPase. In regional studies of the forebrain involving ischemia for 60 min plus 30 min reflow, damage to Na+, K+-ATPase was evident in the cerebrum, hippocampus, striatum and thalamus, while the hypothalamus and olfactory bulb were spared. Pretreatment of gerbils with allopurinol, clonazepam or combinations of thiopental plus either indomethacin or methylprednisolone offered protection to cerebral Na+, K+-ATPase subsequent to secondary ischemia. With only minor exceptions (striatum) neither Ca2+, Mg2+- nor Mn2+-ATPase were altered by stroke or treatment with drugs.
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PMID:Classification of ischemic-induced damage to Na+, K+-ATPase in gerbil forebrain. Modification by therapeutic agents. 299 3

We have employed concurrent 31P- and 23Na-nuclear magnetic resonance (NMR) spectroscopy in conjunction with the paramagnetic shift reagents dysprosium-chelated tripolyphosphate and triethylenetetramine-hexa-acetic acid to observe the intracellular sodium and phosphorus signals in rat leg muscle. With induced ischemia in the leg, we find slowly falling phosphorylation potential. At a critical value of, associated with energetic failure of the Na+-K+ antiport, the intracellular sodium signal begins to increase. We find the following critical values: log, 3.12 +/- 0.32; pH, 6.86 +/- 0.13; Na+ influx with and without ouabain, 5.1 +/- 4.3 and 4.0 +/- 1.3 mol.l-1.h-1, respectively.
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PMID:Intracellular sodium flux and high-energy phosphorus metabolites in ischemic skeletal muscle. 342 18

A rabbit spinal cord ischemia model was used to study the effects of focal ischemia on the tissue concentrations of serotonin, 5-hydroxyindole acetic acid, and norepinephrine. Ischemia induced by abdominal aorta occlusion caused both serotonin and norepinephrine concentrations to decline in the most ischemic areas of the spinal cord by 55 minutes. In marginally perfused adjacent areas, serotonin concentrations transiently declined at 14 and 20 min. After the onset of ischemia and then returned to normal. The minimum was reached at the same time when previous studies showed damage had become irreversible in more ischemic regions. Concentrations of 5-hydroxyindole acetic acid did not change at any time and norepinephrine declined only in the most ischemic areas after damage was irreversible. Thus, permanent serotonin and norepinephrine decreases occur only in areas destined to be destroyed by infarction, but the serotonin returns to normal in marginal tissue that remains viable. These studies suggest that serotonin may be involved in the early stages of irreversible changes during central nervous system ischemia.
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PMID:The effect of ischemia on biogenic amine concentrations in the central nervous system. 619 84

The limitation of conventional histological methods to demonstrate ischemic change of neurons in early phase has been a major drawback in histopathological and pathophysiological studies of cerebral ischemia. Cellular metabolism is disturbed immediately after cessation of the regional circulation and rapid alterations in macromolecular and ultrastructural integrity in neurons may take place before any evidence of histopathological changes could be detectable. To demonstrate ischemic change of neurons more sensitively on a histological level, we applied immunohistochemical method using antiserum to tubulin, a protein of microtubules. As this organelle has been implicated in several important cellular functions such as control of cell shape, intracytoplasmic transport of materials or synaptic transduction, immunohistochemical alterations in microtubules may indicate structural as well as functional damage of neurons. In order to study the ischemic change in neurons, the posterior communicating artery of a gerbil brain was occluded by the method previously reported by us, and the hippocampus, which is one of the most vulnerable structures of the brain to ischemia, was observed. Five or 30 minutes after occlusion, animals were sacrificed by decapitation. Brains were removed, cut coronary vessels and fixed in ethanol-acetic acid (95:5). Tubulin used for this study was extracted from normal gerbil brains and specific antiserum was raised in goats Peroxidase-antiperoxidase method was performed on paraffin sections. Immunohistochemical distribution of tubulin in a normal gerbil brain demonstrated by the present method was in good accordance with the reported electronmicroscopical distribution of microtubules.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Immunohistochemical study of ischemic neuronal damage with antiserum to tubulin, a microtubular protein]. 638 May 43

Characteristics of the temporal elevation of diastolic tension, produced by ischemia-reperfusion in isolated and paced Langendorff's hearts of guinea pigs, were studied. The elevation of diastolic tension corresponded with an elevation of left ventricular end diastolic pressure after a short ischemic period in the isovolumic heart. These phenomena were thought to be a result of incomplete relaxation. The degree of the elevation of diastolic tension depended upon the duration of ischemic period (3-10 min). This elevation was reproducible in one preparation; nearly the same changes were obtained in a second trial after 35 min of reperfusion when the ischemic period was within 5 min. An increment in the pacing rate to 150% of the first trial value doubled the elevation of diastolic tension by the second 5 min ischemia. Inhibition of glycolytic flux by iode acetic acid augmented the elevation after 3 min of ischemia. In addition, 5 min of ischemia with iode acetic acid caused contracture and recovery was slight. On the other hand, either lowering the Ca2+ concentration in the perfusing solution to a half the normal value, or treatment with Ca2+ antagonists (such as diltiazem), reduced the elevation of diastolic tension significantly. Diltiazem also suppressed the increment in elevation produced by a high pacing rate. It can be concluded that the temporal elevation of diastolic tension during reperfusion reflects the ischemic failure of the heart. This change is presumably due to intracellular Ca2+ overload or accumulation. In addition, since ischemic changes were reproducible in this preparation, it is a useful model for estimating the effects of drugs on the ischemic heart.
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PMID:Ischemia-reperfusion induced elevation of diastolic tension in the isolated guinea pig heart and the effects of calcium antagonists. 685 62

The effect of L-arginine, the precursor of nitric oxide, on ischemic dopamine release from the striatum was investigated in Mongolian gerbils subjected to bilateral carotid artery occlusion (15 min) alone or with reflow (2 h). Dopamine and its metabolites were measured in the striatal extracellular space dialysate after continuous perfusion (2 microliters/min) of artificial extracellular fluid in the presence or absence of 15 mmol/liter L- or D-arginine or 1 mmol/liter nitro-L-arginine. L-Arginine but not D-arginine increased the striatal content of dopamine in pre- and postischemia whereas it lowered the levels of dopamine and 3-methoxytyramine induced by ischemia. In contrast, nitro-L-arginine reduced the preischemic levels of dopamine and 3,4-dihydroxyphenyl-acetic acid, and had no effect on the ischemic release of dopamine. These findings indicate that L-arginine stereospecifically modified the ischemic release and metabolism of dopamine. The data also suggest that the basal level of nitric oxide is not involved in dopamine release during ischemia but may participate in regulating dopamine release under physiological conditions.
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PMID:Modulation of striatal dopamine release in cerebral ischemia by L-arginine. 765 86

The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and reperfusion, using intracerebral microdialysis as the sampling technique. In rats subjected to 20 min forebrain ischemia by four-vessel occlusion, the concentrations of adenosine (Ade), inosine (Ino) and hypoxanthine (Hyp) were found to rise markedly. These changes were accompanied by dramatically elevated levels of aspartate (Asp), glutamate (Glu), taurine (Tau), gamma-aminobutyric acid (GABA), dopamine (DA) and norepinephrine (NE), all of which gradually returned to baseline following reperfusion. Concomitantly, the levels of metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA) and xanthine (Xan) decreased during ischemia and gradually recovered 60-90 min after reperfusion. It was concluded that during global brain ischemia, the ECF is flooded with both potentially harmful (e.g. Asp, Glu, DA) and protective (e.g. Tau, GABA, Ade) agents.
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PMID:Changes of monoamines, purines and amino acids in rat striatum as measured by intercerebral microdialysis during ischemia/reperfusion. 771 61

A new histofluorescence method by HPAA (p-hydroxyphenyl acetic acid) for free radicals in the brain tissue was devised to study neuronal damage induced by ischemia. Cerebral ischemia was produced in rats by injection of plastic microspheres and arachidonic acid (AA) into the right carotid artery. The concentration of malondialdehyde (MDA; free radical) in cerebral cortex of aminotriazol (an H2O2-dependent inhibitor of catalase) treated rats 2 h after stroke was 6.33 times the level before infarction, while the concentration of MDA in h-r SOD (free radical-scavenging enzyme) treated rats 2 h after stroke was significantly lower than in untreated rats. The histochemical findings demonstrated marked H2O2 production around blood vessels occluded by microspheres in the cerebral cortex of the aminotriazole treated rats 2 h after stroke together with disruption of the BBB. Light microscopical findings demonstrated extensive edematous changes in the aminotriazole treated rats 2 h after stroke, while pathological damage in SOD treated rat brains was absent or minimal. We conclude that free radicals are formed during ischemia, and that AA appears to be a major source of activated oxygen radicals. The findings indicate that SOD is protective against ischemia-induced neuronal damage.
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PMID:Histochemical demonstration of free radicals (H2O2) in ischemic brain edema and protective effects of human recombinant superoxide dismutase on ischemic neuronal damage. 797 74

Alpha-phenyl-tert-butyl-nitrone (PBN) a spin adduct forming agent is believed to have a protective action in ischemia-reperfusion injury of brain by forming adducts of oxygen free radicals including .OH radical. Electron paramagnetic resonance (EPR) has been used to both detect and monitor the time course of oxygen free radical formation in the in vivo rat cerebral cortex. Cortical cups were placed over both cerebral hemispheres of methoxyflurane anesthetized rats prepared for four vessel occlusion-evoked cerebral ischemia. Prior to the onset of sample collection, both cups were perfused with artificial cerebrospinal fluid (aCSF) containing the spin trap agent alpha-(4-pyridyl-1-oxide)-N-tert butylnitrone (POBN 100 mM) for 20 min. In addition 50 mg/kg BW of POBN was administered intraperitoneally (IP) 20 min prior to ischemia in order to improve our ability to detect free radical adducts. Cup fluid was subsequently replaced every 15 min during ischemia and every 10 min during reperfusion with fresh POBN containing CSF and the collected cortical superfusates were analyzed for radical adducts by EPR spectroscopy. After a basal 10 min collection, cerebral ischemia was induced for 15 or 30 min (confirmed by EEG flattening) followed by a 90 min reperfusion. .OH radical adducts (characterized by six line EPR spectra) were detected during ischemia and 90 min reperfusion. No adduct was detected in the basal sample or after 90 min of reperfusion. Similar results were obtained when diethylenetriaminepenta-acetic acid (100 microM; DETAPAC) a chelating agent was included in the artificial CSF. Systemic administration of PBN (100 mg/kg BW) produced a significant attenuation of radical adduct during reperfusion. A combination of systemic and topical PBN (100 mM) was required to suppress .OH radical adduct formation during ischemia as well as reperfusion. PBN free radical adducts were detected in EPR spectra of the lipid extracts of PBN treated rat brains subjected to ischemia/reperfusion. Thus this study suggests that PBN's protective action in cerebral ischemia/reperfusion injury is related to its ability to prevent a cascade of free radical generation by forming spin adducts.
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PMID:alpha-Phenyl-tert-butyl-nitrone (PBN) attenuates hydroxyl radical production during ischemia-reperfusion injury of rat brain: an EPR study. 829 48


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