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)

Susceptibility to cadmium (Cd) hepatotoxicity differs among inbred strains of mice. For example, C3H/HeJ mice are sensitive to Cd-induced hepatotoxicity, whereas DBA/2J mice are resistant. The mechanism of genetic predisposition to Cd hepatotoxicity is unknown. A contemporary theory for acute target organ intoxication maintains that Cd initially damages vascular endothelium and parenchymal cell injury is a secondary event that results from localized ischemia. In the present study, the hypothesis that hepatic endothelial cells (EC) of C3H mice are more susceptible to Cd toxicity than those of DBA mice was tested. Hepatic parenchymal and endothelial cells were grown separately on monolayer cultures for 22 h and subsequently treated with various concentrations of Cd. Hepatocellular toxicity was assessed by lactate dehydrogenase leakage and intracellular K+ loss, whereas endothelial cell injury was assessed by trypan blue exclusion and the inhibition of protein synthesis. The susceptibility of hepatocytes to the cytotoxic effects of Cd was identical between strains. In contrast, the vulnerability of EC to Cd intoxication was strain-dependent. When exposed to 2.5-10.0 microM Cd, EC of Cd-sensitive mice were more susceptible to the cytotoxic effects of Cd than those of Cd-resistant mice. Basal metallothionein (MT) levels as well as Cd uptake into EC were similar in the two strains. Following Cd exposure, EC of Cd-sensitive mice accumulated similar amounts of MT as EC of Cd-resistant mice. These observations suggest that the microvasculature in livers of inbred mice is the target tissue responsible for strain-dependent susceptibility to Cd-induced liver injury. The mechanisms that account for this genetic variation in endothelial cell response to Cd are unknown, but do not appear to be related to the cellular disposition of Cd nor to a defect in the metabolism of MT.
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PMID:Cadmium-induced hepatic endothelial cell injury in inbred strains of mice. 145 24

We have attempted to reconstruct in vitro the events that may occur in vivo during reperfusion injury after ischemia in the central nervous system. The phenomenon is induced by previous exposure to low calcium solutions ("calcium paradox") before the reperfusion episode. Intracellular calcium alterations during reperfusion of human astrocytoma U1242MG cells have been investigated with microspectrofluorimetry using the calcium-sensitive dye fura-2. Cells were perfused in calcium-free buffer solution for 30 min and then re-exposed to the control buffer solution (1.5 mM CaCl2). [Ca2+]i increased up to 3.5 times control levels during the reperfusion period. The mechanism of the increase was also investigated. Addition of TTX (2 microM) or choline chloride sodium substitution during perfusion with low calcium prevented the [Ca2+]i increase during reperfusion. Reperfusion increases in [Ca2+]i were exacerbated by low potassium in the perfusion medium, but unaltered by the calcium channel blockers cadmium (100 microM) and nickel (100 microM). In a similar manner, flunarizine (10 microM) and cadmium (100 microM) were unable to modify reperfusion [Ca2+]i alterations. Low sodium in the reperfusion medium produced significant increases in [Ca2+]i if preceded by low potassium and calcium perfusion. The viability of cells after 24 h of incubation after the insult produced by exposure to Ca(2+)-free media for 30 min was also investigated. Compared with control groups, the groups treated with Ca(2+)-free media for 30 min had a decreased number of surviving cells and morphological alterations indicative of cell pathology. The relative number of cytotoxic cells was increased by maneuvers (low potassium perfusion) that presumably blocked the Na/KATPase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reperfusion paradox: a novel mode of glial cell injury. 153 10

The production of oxygen free radicals can be stimulated by excess iron, cadmium, nickel, and the like. Inversely, copper, zinc, and selenium inhibit production, either via their own action or via antiradical metalloenzymes. The study involved determining the effect of zinc deficiency combined with chronic ethanol administration on the status of blood and tissue free radicals, as well as on cardiac function in isolated, perfused rats' hearts. Animals were fed a basic diet containing residual zinc at 0.2-0.3 ppm. Following a zinc deficiency lasting 5 wk, which during the last 4 wk was accompanied by chronic ethanol administration, hearts were submitted to ischemia for 30 min in vitro, followed by reperfusion. Biochemical analyses (zinc, superoxide dismutase, malondialdehyde, conjugated dienes, and so on) were performed in the blood and in the homogenates of different organs. The experimental zinc deficiency caused a slight decrease of superoxide dismutase activity, accompanied by increased production of peroxidated lipids. Ethanol administration appeared to increase the levels of peroxidated lipids in the heart. Finally, the combination of zinc deficiency and ethanol administration had very harmful effects, especially on lipid peroxidation and contractile function of the isolated, perfused heart in preischemic conditions.
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PMID:Zinc deficiency, ethanol, and myocardial ischemia affect lipoperoxidation in rats. 172 83

A dual-laser system (helium-cadmium and pulsed dye) capable of continuous computer analysis of spectroscopic characteristics of tissue fluorescence, which can distinguish atherosclerotic plaque from components of normal arterial wall, was used to deliver laser energy to ablate plaque. During a 1-year period this system was used to facilitate balloon angioplasty of short (3 to 17 cm) total occlusions of the superficial femoral or popliteal arteries only when standard angioplasty techniques were ineffective. During the year of the study, in one institution 415 patients were subjected to arteriography of the lower extremities for leg ischemia (397 for limb salvage indications). Standard angioplasty techniques were used in 94 of these patients; 218 patients were unsuitable for standard angioplasty, did not fulfill criteria for "smart" laser treatment, and underwent standard bypass operations. Only 11 patients (plus six others in the second institution) requiring treatment fulfilled the criteria for use of the "smart" laser. In 10 patients the occluding lesion was traversed by the laser wire (diameter 0.021 inch), and luminal patency was effectively restored by balloon angioplasty to greater than or equal to 70% of the most normal-appearing segment of that artery. Satisfactory luminal patency has persisted for 2 to 12 months (mean 6 months) in nine patients; the lesion in the tenth patient restenosed at 3 months. The laser procedure was unsuccessful in all three patients with occlusions greater than 10 cm and in four others. Although there were three microperforations with the laser wire, there were no clinically significant complications.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early experience with the smart laser in the treatment of atherosclerotic occlusions. 182 7

Lipid peroxidation disrupts membrane integrity and causes structural and functional alterations in ischemic tissues. Taurine and ketamine are putative ischemic protectants that affect Ca2+ influx. Here we report the influence of these compounds on lipid peroxidation in subcellular fractions, isolated cells and intact tissue from bovine retinas. P2 membrane fractions and isolated cells were exposed to the lipid peroxidation inducers cadmium chloride (200 microM) or L-ascorbic acid (1 mM) in the presence of 0-50 mM taurine, 0-10 mM ketamine, 1 mM kynurenic acid or 1 mM dextromethorphan. The latter compounds are N-methyl-D-aspartate receptor antagonists. Lipid peroxidation in isolated eyes reperfused after 1 h of ischemia either with or without protectants was determined by thiobarbituric acid assay. Glutathione was measured in isolated retinas subjected in vitro to simulated ischemia (no glucose or oxygenation) for 60 min either alone or in the presence of taurine or ketamine. Ketamine inhibited chemical- or ischemia-induced lipid peroxidation as well as ischemic glutathione depletion. Under the same conditions, taurine failed to affect lipid peroxidation or glutathione. The data show a direct effect of ketamine on lipid peroxidation and point to separate mechanisms of action for ketamine and taurine.
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PMID:Effects of taurine and ketamine on bovine retinal membrane lipid peroxidation. 183 70

Technetium 99m-hexakis-2-methoxy-2-methylpropyl-isonitrile (Tc-MIBI) is a promising new myocardial perfusion imaging agent producing excellent rest images. Imaging, however, will need to be performed with exercise or dipyridamole to detect ischemia and to differentiate salvaged but still ischemic myocardium from scar. Accordingly, 12 dogs were given mild-to-moderate left circumflex coronary stenoses (group 2), and 10 dogs were given severe stenoses (group 3). In five control dogs (group 1), there was no stenosis. After an intravenous infusion of dipyridamole (0.08 mg/kg/min for 4 minutes), Tc-MIBI was injected into the right atrium. Over the next 4-hour study period, myocardial Tc-MIBI activities were continuously monitored in both the left anterior descending (LAD) (normal) and left circumflex (LCx) (ischemic) coronary artery (ischemic) zones using miniature cadmium telluride radiation detectors and serial gamma camera images were acquired when necessary. Tc-MIBI was rapidly taken up by nonischemic, mild-to-moderate, and severe ischemic myocardium. The initial myocardial uptake of Tc-MIBI was linearly related (r = 0.97) to regional myocardial blood flow at rates up to 2.0 ml/min/g. After the initial uptake, the mean 4-hour fractional myocardial clearance was similar between the control (0.09 +/- 0.03 [+/- SEM]) and group 2 (0.07 +/- 0.03) and group 3 (0.09 +/- 0.03) ischemic zones. Tc-MIBI blood clearance was rapid and biexponential with an initial fast clearance phase followed by a slow clearance phase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myocardial kinetics of Tc-MIBI in canine myocardium after dipyridamole. 229 67

To investigate the relationship between left ventricular function and electrical changes during myocardial ischemia, ambulatory left ventricular function monitoring and ECG recording were made during the ergometer exercise test in 14 patients with coronary artery disease. An ambulatory ventricular function monitor consists of a small cadmium telluride (CdTe) radionuclide probe (250 g) affixed to the patient's chest wall, a preamplifer (10 g), and a portable data acquisition unit (600 g). Left ventricular time-activity curves were recorded continuously using this monitor, and the end-systolic count (volume), end-diastolic count (volume) and ejection fraction were calculated after background subtraction. Twenty-eight exercise tests were performed in the supine and upright positions. In 15 tests, left ventricular dysfunction, i.e., an increase in the end-systolic count (greater than or equal to 10%) and a decrease in ejection fraction (greater than or equal to 5%), and ST depression (greater than or equal to 0.1 mV) were observed. In these 15 tests, exercise duration was 362 +/- 27 sec. Left ventricular dysfunction occurred earlier than ST depression and the time difference was 97 +/- 19 sec. Left ventricular function recovered 33 +/- 8.5 sec after discontinuation of exercise, while ST depression continued for the additional 85 +/- 18.5 sec after recovery of left ventricular function. In conclusion, 1) left ventricular dysfunction occurs earlier than electrical changes during exercise-induced ischemia; 2) left ventricular dysfunction improves earlier than electrical changes after exercise; and 3) the same temporal sequence exists in the restoration from myocardial ischemia.
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PMID:Sequence of mechanical and electrical changes during myocardial ischemia: assessment by an ambulatory left ventricular function monitor. 326 33

The enzyme xanthine: acceptor oxidoreductase found in rat heart equilibrates between three forms differing in electron acceptor specificity. Form D transfers electrons exclusively to NAD+ and accounts for 85% of total oxidoreductase activity. Form O transfers electrons to molecular oxygen and accounts for 8%. The D/O form prefers NAD+, but without NAD+ transfers electrons to oxygen. Interconversion from D to O and O to D forms is catalyzed by sulfhydryl group-modifying reagents: Cd2+, Cu2+, disulfiram, and heating with dithiothreitol. This suggests that sulfhydryl groups participate in the first stage of enzyme conversion. The NADH/NAD+ concentration ratio may regulate the dehydrogenase activity of xanthine:acceptor oxidoreductase (NAD+-dependent activity of D and D/O forms). Accumulating NADH inhibits hypoxanthine hydroxylation. The amount of form O increases during cardiac ischemia, facilitating superoxide radical-ion generation. Also, NADH/NAD+ does not regulate form O, promoting adenylate nucleotide pool depletion, especially in the heart which has low de novo purine nucleotide synthesis.
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PMID:Three forms of xanthine: acceptor oxidoreductase in rat heart. 346 36

Metabolic, mechanical, thermal, and chemical injury induced ornithine decarboxylase (ODC) activity in rat brain. A two- to sixfold increase in ODC activity was measured at 5-9 h after different modes of injury to the brain. During the early phase of recovery from transient ischemia, when average protein synthesis was less than 50% of control, ODC activity was increased nearly fivefold. The rise in activity could be blocked by anisomycin, or reduced by intracerebral injections of actinomycin D. Drilling burr holes into the skull, injection of the vehicle for actinomycin D, hyperthermia, and freezing lesions all caused increased ODC activity. Neurotoxic chemicals (ammonia, methionine sulfoximine, acrylamide, carbon tetrachloride, and anisomycin) also increased brain ODC activity, whereas other chemicals (mannitol and valine) did not. Treatments known to stimulate the synthesis of heat shock proteins (carotid occlusion, hyperthermia, Cd2+, canavanine, and ethanol) induced ODC activity in the liver, whereas only hyperthermia and ethanol caused significant increases in spleen ODC activity. All increases in ODC activity were blocked by difluoromethylornithine, an irreversible inhibitor of ODC. The cellular response to noxious or stressful stimuli includes the synthesis of a small number of proteins of unknown functions; ODC may be one of these "heat shock" or "trauma" proteins.
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PMID:Induction of brain ornithine decarboxylase during recovery from metabolic, mechanical, thermal, or chemical injury. 642 97

The possible involvement of metallothionein (MT) gene expression dysfunction was examined in a strain of mouse which is unusually sensitive to cadmium toxicity, the C3H. C3H mice, and the relatively cadmium-insensitive Swiss mice, were injected sc with 20 microM CdCl2/kg body wt. This dose caused liver damage, visible at the light microscopic level, in the C3H but not the Swiss mice. These studies showed that MT-I mRNA and MT protein accumulation, as well as binding of cadmium by MT, were very similar in the two strains. These data suggested that altered expression of MT in the hepatic parenchyma was not a factor in the C3H hypersusceptibility. An electron microscopic examination of the early effects of cadmium injection indicated that the primary targets for toxicity in the C3H liver may be the endothelial cells. It is hypothesized that the widespread damage seen at later times resulted, secondarily, from ischemia produced in response to endothelial cell damage.
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PMID:Cadmium hypersusceptibility in the C3H mouse liver: cell specificity and possible role of metallothionein. 648 95


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