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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bifemelane hydrochloride (bifemelane), idebenone and indeloxazine hydrochloride (indeloxazine) are used clinically to reduce apathy and other emotional disturbances in patients with cerebrovascular disease. In gerbil brains, ischemia affects many monoaminergic neurotransmitters and their metabolites. In the present study, the effects of treatment with bifemelane, idebenone and indeloxazine on ischemia-induced changes in monoamines and their metabolites were studied in ischemic gerbil brains. Although these drugs had no effect on the monoaminergic neurotransmitters or their metabolites in sham-operated animals, in the ischemic brains both dopamine and serotonin turnovers were abnormal after idebenone or indeloxazine treatment. Bifemelane, in contrast, tended to correct the ischemia-induced changes in the dopaminergic and serotonergic systems in the cerebral cortex, hippocampus and thalamus + midbrain. From the present results and those in previous reports, we conclude that bifemelane is more appropriate than idebenone or indeloxazine as a treatment for the ischemia-induced changes in monoaminergic neurotransmitter systems.
J Neural Transm Gen Sect 1992
PMID:Comparison of the effects of bifemelane hydrochloride, idebenone and indeloxazine hydrochloride on ischemia-induced changes in brain monoamines and their metabolites in gerbils. 138 58

1. A comparative study on isolated guinea pig hearts was carried out to determine the effects of ATP and verapamil as cardioplegic additives. 2. The hearts were arrested by one of the plegic solutions: I, potassium 20 mmol/l; II, potassium 20 mmol/l+verapamil 1.1 mumol/l; III, potassium 20 mmol/l+ATP 10 mmol/l. After 45 min of hypothermic ischemia, the hearts were reperfused by Krebs-Henseleit buffer. 3. Postischemic percentage change of myocardial functions (heart rate, contractility, heart work) and tissue enzymes (LDH, SGOT, SGPT) were compared between the groups. 4. Although a rapid cardiac arrest could be obtained by verapamil added cardioplegia. Postischemic myocardial recovery was much better with ATP added cardioplegic solutions.
Gen Pharmacol 1992 Sep
PMID:Effect of ATP and verapamil as cardioplegic additives in the isolated guinea pig heart. 142 35

1. We studied the postischemic time-course of dopamine D1 receptors in selectively vulnerable areas in the gerbil using receptor autoradiography. 2. [3H]SCH 23390 was used to label dopamine D1 receptors and transient cerebral ischemia was induced for 10 min. 3. [3H]SCH 23390 binding showed no significant alteration in selectively vulnerable areas at an early stage (1-24 hr) of recirculation. Thereafter, [3H]SCH 23390 binding showed a significant reduction in most selectively vulnerable areas 48 hr or 7 days of recirculation. The ventromedial striatum and dentate gyrus which were resistant to ischemia also exhibited a significant reduction in [3H]SCH 23390 binding. 4. Especially, marked reduction was noted in the dorsolateral striatum. However, this reduction in the dorsolateral striatum was not seen early in the recirculation prior to morphological neuronal damage. 5. The result suggests that transient cerebral ischemia can cause a severe reduction in dopamine D1 receptors in most selectively vulnerable areas. Furthermore, they suggest that dopamine D1 transmission is not always responsible for the evolution of ischemic brain damage. 6. These findings are discussed in relation to the mechanism of ischemic brain damage.
Gen Pharmacol 1992 Nov
PMID:Autoradiographic analysis of dopamine D1 receptors in the gerbil brain following transient cerebral ischemia. 148 17

1. An experimental comparative study on isolated guinea pig hearts was carried out to determine the effect of dipyridamole added to the reperfusion solution on myocardial recovery after global ischemia. 2. After 20 min of normothermic ischemia two groups of solutions: (1) Krebs solution; (2) Krebs + dipyridamole 20 micrograms/l (10 experiments in each group) were used for reperfusion. 3. Postischemic myocardial functions (heart rate, ventricular contractility, heart work) and tissue enzymes (CPK-MB, LDH) were compared with their preischemic values. 4. Addition of dipyridamole 20 micrograms/l to reperfusion solution improved postischemic myocardial functions and decreased myocardial injury.
Gen Pharmacol 1992 May
PMID:Dipyridamole induced myocardial recovery after global ischemia. 151 53

1. We investigated the alterations in binding sites of three major second messengers, phorbol 12,13-dibutyrate, inositol 1,4,5-trisphosphate and forskolin following transient cerebral ischemia in gerbils, and examined the effects of a novel vinca alkaloid derivative, vinconate against the alterations in the binding of the second messengers following ischemia. 2. Transient cerebral ischemia produced by bilateral occlusion of the common carotid arteries was induced for 10 min, and intraperitoneal administration of vinconate (100 mg/kg and 300 mg/kg) was given 10 min before ischemia. 3. Morphological study indicated that transient ischemia can produce severe neuronal damage in striatum, hippocampal CA1 sector and hippocampal CA3 sector. 4. Transient cerebral ischemia caused the postischemic alterations in the binding of three second messengers. 5. The postischemic alterations in the binding of second messengers were ameliorated by pretreatment with vinconate. This effect was especially observed in the striatum which was most vulnerable to ischemia. 6. These findings are discussed in relation to the mechanism of ischemic neuronal damage.
Gen Pharmacol 1992 Jan
PMID:Protective effect of a novel vinca alkaloid derivative, vinconate, against alterations in binding sites of second messengers after transient cerebral ischemia in gerbils. 159 19

1. We investigated the effect of a novel vinca alkaloid derivative, vinconate, against brain damage after focal ischemia induced by a middle cerebral artery (MCA) occlusion in rats. 2. Persistent focal ischemia was induced by 6 hr, and vinconate (50 and 100 mg/kg) was given intraperitoneally twice 10 min and 3 hr after MCA occlusion. 3. Focal ischemia produced the disturbance of glucose metabolism, the increase of water content and the impairment of protein synthesis in the surrounding occluded MCA territory. 4. Vinconate was effective in preventing marked reduction of cerebral glucose utilization in the areas surrounding the occluded MCA territory. 5. Vinconate significantly reduced an increase of water content in the surrounding the occluded MCA territory. 6. Preliminary L-[methyl-14C]methionine autoradiographic study also indicated that vinconate can partly prevent a severe impairment of protein synthesis after focal ischemia. 7. The results indicate that vinconate may ameliorate the disturbance of glucose metabolism, brain edema and the impairment of protein synthesis after persistent focal ischemia, and they also suggest that vinconate has a beneficial effect against brain damage.
Gen Pharmacol 1992 Jan
PMID:Protective effect of vinconate, a novel vinca alkaloid derivative, on glucose utilization and brain edema in a new rat model of middle cerebral artery occlusion. 159 23

The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.
Gen Hosp Psychiatry 1992 May
PMID:Electrocardiographic evidence of myocardial injury in psychiatrically hospitalized cocaine abusers. 160 Dec 97

Antagonists for the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor may have therapeutic potential as neuroprotectant agents in conditions of neuronal degeneration that include brain ischemia, Huntington's chorea, and Alzheimer's disease. Here we have investigated the pharmacological actions of LY274614, a structurally novel competitive NMDA receptor antagonist, for pharmacological selectivity and neuroprotectant effects following systemic administration. LY274614 potently displaced NMDA receptor ([3H]CGS19755) binding (IC50 = 58.8 +/- 10.3 nM), but had no appreciable affinity at [3H]AMPA or [3H]kainate receptor sites at up to 10,000 nM. NMDA-induced convulsions in neonatal rats or NMDA-induced lethality in mice are potently and selectively antagonized by i.p. or p.o. LY274614. Oral doses showed a delayed but prolonged duration of effect. In adult rats, the neurodegenerative effects (loss of choline acetyltransferase activity) following the intrastriatal infusions of NMDA or quinolinate, but not kainate, were prevented by LY274614 (2.5 to 20 mg/kg i.p.). LY274614 is an effective neuroprotectant agent against NMDA receptor-induced toxicity when administered systemically and is a promising therapeutic agent for conditions where glutamate plays a role in the pathology of neuronal degeneration.
J Neural Transm Gen Sect 1991
PMID:Neuroprotectant effects of LY274614, a structurally novel systemically active competitive NMDA receptor antagonist. 183 88

The role of the Na/Ca exchanger in the control of cellular excitability and tension development is a subject of current interest in cardiac physiology. It has been suggested that this coupled transporter is responsible for rapid changes in intracellular calcium activity during single beats, generation of plateau currents, which control action potential duration, and control of intracellular sodium during Na/K pump suppression, which may occur during terminal states of ischemia. The actual behavior of this exchanger is likely to be complex for several reasons. First, the exchanger transports two ionic species and thus its instantaneous flux rate depends on both intracellular sodium and calcium activity. Secondly, the alteration in intracellular calcium activity, which is caused by a given transmembrane calcium flux, and which controls the subsequent exchanger rate, is a complex function of available intracellular calcium buffering. The buffers convert the ongoing transmembrane calcium fluxes into changes in activity that are a small and variable fraction of the change in total calcium concentration. Using a number of simple assumptions, we model changes in intracellular calcium and sodium concentration under the influence of Na/Ca exchange, Na/K ATPase and Ca-ATPase pumps, and passive sodium and calcium currents during periods of suppression and reactivation of the Na/K ATPase pump. The goal is to see whether and to what extent general notions of the role of the Na/Ca exchanger used in planning and interpreting experimental studies are consistent with its function as derived from current mechanistic assumptions about the exchanger. We find, for example, that based on even very high estimates of intracellular calcium buffering, it is unlikely that Na/Ca exchange alone can control intracellular sodium during prolonged Na/K pump blockade. It is also shown that Na/Ca exchange can contaminate measurements of Na/K pump currents under a variety of experimental conditions. The way in which these and other functions are affected by the dissociation constants and total capacity of the intracellular calcium buffers are also explored in detail.
J Gen Physiol 1990 Mar
PMID:Interaction of intracellular ion buffering with transmembrane-coupled ion transport. 215 93

Changes in intra- and extracellular free calcium concentration were evaluated with ion-selective microelectrodes during periods of anoxia and ischemia in three different regions of intact rat brain. Recordings stable for at least 2 min and in most cases for 4-6 min were chosen for analysis. Under normoxic conditions neuronal [Ca2+]i varied between less than 10(-8) and 10(-7) M from cell to cell but no systematic regional differences were observed. Elimination of O2 or interruption in blood flow caused, within 30-60 s, slight intracellular alkalinization followed by a small rise in [Ca2+]i, a mild degree of hyperpolarization, and disappearance of electrical activity in the cortex, in that order. It is postulated that a decline in cellular energy levels, as manifested by H+ uptake associated with creatine phosphate hydrolysis, leads to an increase in [Ca2+]i, which activates Ca2(+)-dependent K+ channels and consequently enhances gK. 2-4 min later there was a sudden, large rise in [K+]e, a fall in [Ca2+]e and a rapid elevation of [Ca2+]i. The magnitude of the latter was greatest in a high proportion of hippocampal neurons in area CA1 and some cortical cells, while it was smallest and relatively delayed in thalamic neurons. In the hippocampus area CA1 increases in [Ca2+]i to as much as 6-8 x 10(-4) were observed; some of these could be reversed when O2 or blood flow were restored to normal. Pretreatment of animals with ketamine and MK-801, antagonists of excitatory amino acid transmitters, markedly slowed and decreased the rises in [Ca2+]i. The effects of the two agents were most pronounced in the hippocampus. It is concluded that the receptor-operated channels are largely responsible for Ca2+ entry into certain cells during hypoxia/ischemia. This pathway may be of primary importance in parts of the hippocampus and cortex, regions of the brain that are particularly vulnerable to O2 deprivation and which receive high glutamatergic input and have an abundance of excitatory amino acid receptors.
J Gen Physiol 1990 May
PMID:Intracellular and extracellular changes of [Ca2+] in hypoxia and ischemia in rat brain in vivo. 216 31


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