Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Examples of toxic cardiomyopathies of various characteristics are presented. Daunomycin and doxorubicin, antineoplastic drugs, cause multifocal cardiomyopathies and intractable heart failure by cardiotoxic mechanisms; these effects are delayed and related to the cumulative dose. Cobalt caused diffuse vacuolar cardiomyopathy in chronic beer drinkers. The development of fulminant heart failure was the function of factors that increased the adsorption of cobalt or sensitized the myocardium to its cytotoxic effect. Beta-adrenergic receptor stimulant bronchodilators like isoproterenol or vasodilating antihypersensitive drugs like hydralazine are able to produce focal subendocardial necroses. This lesion is due to ischemia brought about by the acute exxagerated pharmacological effects of these compounds.
 ...
PMID:Toxic cardiomyopathies. 79 2

This study demonstrates ischemic cellular swelling in vivo detected as changes in the concentration of 14C-sucrose pre-perfused into the extracellular space (ECS) as an ECS marker. Microdialysis was utilized as a means of perfusion and measurement of the extracellular concentration of 14C-sucrose ([14C-sucrose]e). Concomitant with an abrupt increase in [K+]e at 1-3 min following the ischemia induction, [14C-sucrose]e was also rapidly elevated. Since sucrose is not taken up by either cells or capillaries, the absolute amount of 14C-sucrose in the ECS must be unchanged. The increase therefore appears to represent a relative decrease in water volume in the ECS resulting from a movement of water into the cells, i.e. cellular swelling. Ca(2+)-free perfusate containing Co2+, which has been shown to block excitatory amino acid release during cerebral ischemia, significantly delayed the increase in [14C-sucrose]e and [K+]e. Kynurenic acid, a broad-spectrum antagonist of excitatory amino acids, administered in situ through the dialysis probe also significantly delayed the increase in [14C-sucrose]e and [K+]e. These findings indicate that the early cellular swelling occurring during cerebral ischemia is a result of massive ionic fluxes mediated by excitatory amino acids which are released by a Ca(2+)-dependent exocytotic process from the nerve terminals.
 ...
PMID:Early cellular swelling during cerebral ischemia in vivo is mediated by excitatory amino acids released from nerve terminals. 132 56

We investigated the effects of ischemia-related amphipathic compounds, palmitoylcarnitine (PamCar, 0.5-50 microM) and lysophosphatidylcholine (lysoPtdCho, 5-50 microM) on sodium current (INa) of guinea-pig ventricular myocytes. The cells were perfused with low-Na+ (60 mM) Tyrode's solution, and Ca2+ and K+ currents were blocked by external Co2+ (3 mM) and internal Cs+ (140 mM), respectively. INa was elicited by depolarizing voltage steps from a holding potential of -100 mV at a temperature of 33 degrees C. PamCar (5 microM) decreased the peak INa (attained at -20 mV or -30 mV) from 6.1 +/- 2.1 nA to 3.9 +/- 1.4 nA (n = 11), or by 36.1% within 2 min, and shifted the curve of steady-state INa inactivation by 5.4 mV in the positive direction (from -76.3 +/- 4.6 mV, control to -70.9 +/- 4.0 mV, in PamCar, n = 4). Partial restoration of the amplitude and the shift of the steady-state inactivation curve of INa was attained after washout of PamCar. In contrast, lysoPtdCho at concentrations over 10 microM irreversibly depressed the INa within 0.5-3 min and the reduction of INa was followed by cell contracture or cell death (n = 9). The survival time, defined as a period from the start of lysoPtdCho application to the time of the last successful recording of the INa (before evolution of sudden changes in the holding current), depended on the concentrations of lysoPtdCho. Both PamCar and lysoPtdCho retarded the time course of activation and inactivation of INa.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inhibitory effects of palmitoylcarnitine and lysophosphatidylcholine on the sodium current of cardiac ventricular cells. 155 64

There is a net movement of calcium into brain cells during anoxia and ischemia. This communication examines the mechanisms of this movement in rat hippocampal slices by analyzing changes in 45Ca2+ distribution. The CA1 pyramidal cells are the most sensitive to anoxic/ischemic damage; therefore, our measurements of Ca2+ and high-energy nucleotides are restricted to this region. The increase in intracellular Ca2+ levels during anoxia is not blocked by the Ca2+ channel blocker cobalt, nor is it blocked by N-methyl-D-aspartate receptor antagonists kynurenic acid, D-2-amino-5-phosphonovaleric acid, or ketamine. Kinetic measurements show that the rate of Ca2+ efflux across the plasmalemma during anoxia is sufficiently decreased to account for the increase in intracellular Ca2+. It thus appears that the net increase in calcium does not result from the opening of voltage-sensitive Ca2+ channels, nor from flux through the N-methyl-D-aspartate channel. Rather, it results from inhibition of the adenosine triphosphate-dependent extrusion mechanism for Ca2+. The relation of this conclusion to mechanisms of anoxic cell damage is discussed.
 ...
PMID:Mechanisms of intracellular calcium accumulation in the CA1 region of rat hippocampus during anoxia in vitro. 214 81

The role of oxygen-free radicals for metabolic derangements in the ischemic and reperfused liver is controversial. The effect on hepatic protein synthesis of a 60-minute period of ischemia followed by two hours of reperfusion was studied in four groups of rats with different hepatic contents of the oxygen free radical scavenger glutathione (GSH): group 1, fed rats; group 2, fed rats treated with diethylmaleate (DEM) one hour before use (0.69 mL/kg, i.p.); group 3, 48-hour fasted rats; and group 4, 48-hour fasted rats treated with cobalt-chloride (45 mg/kg, s.c.) ten hours before use. Protein synthesis rates were determined by measuring incorporation of U-14C-leucine into protein in incubated liver slices. Treatment of fed rats with DEM and fasting for 48 hours significantly reduced liver GSH content. The effect of fasting on liver GSH was reversed by treatment with cobalt-chloride. The protein synthesis rate was reduced to approximately 30% of initial value at the end of the ischemic period and recovered to 70% to 100% of initial value after two hours of reperfusion with no differences between the experimental groups. Thus the effect of liver ischemia and reperfusion on protein synthesis was similar in groups of rats with different hepatic GSH contents at the onset of ischemia. The data suggest that oxygen free radicals do not play a major role for the impairment of protein synthesis in the ischemic and reperfused liver.
 ...
PMID:Effects of ischemia and reperfusion on protein synthesis in livers with different glutathione levels. 229 51

The voltage- and time-dependent slow channels in the myocardial cell membrane are the major pathway by which Ca2+ ions enter the cell during excitation for initiation and regulation of the force of contraction of cardiac muscle. These slow channels appear to behave kinetically, on a population basis, as if their gates open, close, and recover more slowly than those of the fast Na+ channels. In addition, the slow channel gates operate over a less negative (more depolarized) voltage range. Tetrodotoxin does not block the slow channels, whereas the calcium antagonistic drugs, Mn2+, Co2+, and La3+ ions do. The slow channels have some special properties, including functional dependence on metabolic energy, selective blockade by acidosis, and regulation by the intracellular cyclic nucleotide levels. Because of these special properties of the slow channels, Ca2+ influx into the myocardial cell can be controlled by extrinsic factors (such as autonomic nerve stimulation or circulating hormones) and by intrinsic factors (such as cellular pH or ATP level). During transient regional ischemia, the selective blockade of the slow channels, which results in depression of the contraction and work of the afflicted cells, might protect the cells against irreversible damage by helping to conserve their ATP content. Reperfusion arrhythmias may be caused by the breakdown of this protective mechanism, in that, upon reperfusion, the Ca2+ slow channels may recover before the cells are capable of handling the greater Ca2+ influx (Fig. 20). As depicted in this figure, the Ca2+ slow channels may recover their function before the ATP level is sufficiently recovered to allow bail-out of the intracellular Ca2+. In addition, the generation of free radicals upon reperfusion may injure the Ca-ATPase and other enzymes involved in Ca2+ metabolism. The net effect of this would be to cause Ca2+ overload of the cells and SR, with subsequent delayed after-depolarizations (DADs) leading to triggered automaticity and arrhythmias. Following blockade of the fast Na+ channels in myocardial cells with TTX or by voltage-inactivating them in 25 mM (K)0, catecholamines, angiotensin-II, histamine, and methylxanthines rapidly allow the production of slowly-rising Ca2+-dependent action potentials by increasing the number of Ca2+ slow channels available for voltage activation and/or their mean open time. Concomitantly, these compounds rapidly elevate intracellular cyclic AMP levels, suggesting that cyclic AMP is somehow related to the functioning of the slow channels. Exogenous cyclic AMP produces the same effect, but much more slowly.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Regulation of calcium slow channels of cardiac muscle by cyclic nucleotides and phosphorylation. 245 7

We hypothesize that enhanced activity of capillary Na,K-ATPase promotes Na+ influx into the brain and causes early edema formation in focal cerebral ischemia. The pharmacologic suppression of brain capillary Na,K-ATPase as a means to ameliorate edema formation was examined using the middle cerebral artery occlusion model in 36 cats. With the help of a catheter inserted into the middle cerebral artery, the ischemic brain area was directly perfused with 10(-5) M ouabain. Perfusion was maintained as intermittent 15-second pulse injections given every 5 (n = 6) or 2 (n = 6) minutes. By this method, the naturally occurring circulatory conditions during ischemia were not altered. Four hours after ischemia, the cortical specific gravity at each of six locations over the ischemic area was compared with the corresponding ischemic blood flow measured by the H2 clearance technique. The results show that ouabain perfused every 2 minutes significantly ameliorated edema formation compared with six control cats perfused with Krebs-Ringer solution. In a separate series of experiments, the Na+ flux across the blood-brain barrier was studied by injecting 22NaCl together with an intravascular reference (cobalt-57-labeled microspheres 15 microns in diameter) into the ischemic area. The brain uptake index of 22Na was markedly increased in the ischemic cortex of six control cats; ouabain treatment in six cats suppressed the increase of Na+ influx. The results support our hypothesis that brain capillary Na,K-ATPase activity increases during early focal ischemia, leading to enhanced Na+ together with H2O flux across the blood-brain barrier.
 ...
PMID:Effect of enhanced capillary activity on the blood-brain barrier during focal cerebral ischemia in cats. 247 24

The uptake and release of D-[3H]aspartate (used as a tracer for endogenous glutamate and aspartate) were studied in cultured glutamatergic neurons (cerebellar granule cells) and astrocytes at normal (5 mM) or high (55 mM) potassium and under conditions of hypoglycemia, anoxia or "ischemia" (combined hypoglycemia and anoxia). In glutamatergic neurons it was found that "ischemic" conditions led to a 2.4-fold increase in the potassium-induced release of D-[3H]aspartate as compared to normal conditions. Hypoglycemia or anoxia alone affected the release only marginally. The ischemia-induced induced increase in the evoked D-[3H]aspartate release was shown to be calcium-dependent. In astrocytes no difference was found in the potassium-induced release between the four conditions and the K+-induced release was not calcium-dependent. The uptake of D-[3H]aspartate was found to be stimulated at high potassium in both glutamatergic neurons (98%) and in astrocytes (70%). This stimulation of D-aspartate uptake, however, was significantly reduced under conditions of anoxia or "ischemia" in both cell types. In glutamatergic neurons (but not in astrocytes) hypoglycemia also decreased the potassium stimulation of D-aspartate uptake. In a previous report it was shown, using the microdialysis technique, that during transient cerebral ischemia in vivo the extracellular glutamate content in hippocampus was increased eightfold. In the present paper it is shown that essentially no increase in extracellular glutamate is seen under ischemia when the perfusion is performed using calcium-free, cobalt-containing perfusion media. The results from the in vitro and in vivo experiments indicate that the glutamate accumulated extracellularly under ischemia in vivo originates from transmitter pools in glutamatergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cellular origin of ischemia-induced glutamate release from brain tissue in vivo and in vitro. 286 Feb 6

We present preliminary findings on the effectiveness of panretinal photocoagulation in preventing neovascular glaucoma in eyes with radiation-induced ocular ischemia. Our study group consisted of 20 patients who developed radiation-induced ocular ischemia following cobalt-60 plaque radiotherapy for a choroidal or ciliary body melanoma. Eleven of the 20 patients were treated by panretinal photocoagulation shortly after the diagnosis of ocular ischemia, but nine patients were left untreated. In this non-randomized study, the rate of development of neovascular glaucoma was significantly lower (p = 0.024) for the 11 photocoagulated patients than for the nine who were left untreated.
 ...
PMID:Panretinal photocoagulation for radiation-induced ocular ischemia. 365 14

The effect of the free radical scavenger glutathione (GSH) on the early post-ischemic liver cell death was studied on liver tissue of the rat. Animals with different pre-ischemic liver GSH contents were subjected to a 90 min period of ischemia, followed by a 3 h period of reperfusion. Cell death was evaluated morphologically by estimating intracellular calcium, using the stain Alizarin red S (ARS), and by dye-exclusion test using Evans blue. The extent of post-ischemic injury was also assessed by registration of the membrane potential (MP) in liver cells. Four groups of animals were studied: 1) fed rats. 2) fed rats pretreated with diethylmaleate. 3) rats fasted for 48 h. 4) fasted rats pretreated with cobalt-chloride. It was found that the early post-ischemic cell death was more extensive in rats with low initial GSH content (group 2 and 3), than in rats with high GSH content (group 1 and 4). It is suggested that GSH is protective against post-ischemic injury, probably by reducing lipid peroxidation.
 ...
PMID:Possible influence of glutathione on postischemic liver injury. 670 58


1 2 3 4 5 6 7 8 9 10 Next >>