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)

The correlation between the three ischemia indicators angina pectoris (AP), ST-segment depression (ST) and excessive pulmonary wedge pressure rise (PCP) during exercise, and the coronary angiographic findings, were analysed in 293 patients without previous transmural myocardial infarction. This patient material consisted of 253 men and 40 women between the age of 20 and 65 years, the mean age being 48. The exercise tests were performed on a bicycle ergometer in supine position and in relatively steady state conditions. Pulmonary wedge pressure was measured by means of a Swan-Ganz floating catheter. The essential findings were: 1. If all three ischemia indicators were positive, the incidence of a positive angiographic finding i.e. a greater than or equal to 50% stenoses in at least one main coronary artery was 96.3%. 2. If only the two classic ischemia indicators were evaluated and positive, the incidence of a positive angiographic finding was only 86.1% (24). This difference is mainly due to false positive results of AP and ST in women. 3. If all three ischemia indicators were negative, the incidence of a negative angiographic finding was 89.2%. 4. If only the two classic ischemia indicators were evaluated and negative the incidence of a negative angiographic finding was as high (87,6% [24]). This lack of difference is due to the fact that patients with a previous intramural infarcion can be free not only of AP and ST but also of PCP during exercise. 5. The combination of AP and PCP, or ST and PCP, is equally reliable in predicting coronary morphology as the classic combination of AP and ST. It follows that PCP measurement is recommended, if one of the classic ischemia indicators cannot be properly evaluated.
 ...
PMID:[Can predictability of coronary angiographic findings be improved by additional measurement of pulmonary wedge pressure during exercise? (author's transl)]. 91 74

Acute cerebral ischemia and reperfusion injury of rabbits was produced by permanently occluding the vertebral arteries and temporarily clamping the common carotid arteries for 30 min. Phencyclidine [1-(phenylcyclohexyl)piperidine, PCP] 40-80 micrograms.kg-1 icv 30 min before ischemia significantly attenuated the decrease of the total power of electroencephalogram (EEG) within 30 min of ischemia and improved the recovery of brain electric activity following reperfusion. PCP 20-80 micrograms.kg-1 dose-dependently suppressed the creatine kinase (CK) release during cerebral ischemia and reperfusion, and PCP 40-80 micrograms.kg-1 reduced brain ischemic damage. These improvements indicated that PCP has protective effects on acute cerebral ischemia and reperfusion injury.
 ...
PMID:Neuroprotective effects of phencyclidine on acute cerebral ischemia and reperfusion injury of rabbits. 144 2

Lamotrigine (LTG), a new anticonvulsant, chemically unrelated to current antiepileptic drugs (AEDs), resembles phenytoin (PHT) and carbamazepine (CBZ) in ability to block hindlimb extension in both the maximal electroshock test and leptazol-induced seizures. Results indicate that LTG may be of value in both partial and generalized seizures. In in vitro studies, LTG has been shown to inhibit veratrine-evoked release of glutamate when a threshold depolarizing concentration (4 micrograms/ml) is used, and also inhibits aspartate release when a larger stimulus is given (10 micrograms/ml). However, LTG does not block potassium-evoked transmitter release. LTG is a less potent inhibitor of the release of gamma-aminobutyric acid (GABA), acetylcholine, noradrenaline, and dopamine. LTG blocks the neurotoxicity of kainic acid in vivo, supporting the in vitro findings, and suggests that the anticonvulsant effect of LTG may be due to inhibition of glutamate release. In a test of working memory and phencyclidine (PCP) discrimination studies, LTG had no effect, indicating no sharing of the same PCP-like side effects associated with NMDA receptor blockade. In the gerbil model of global ischemia, high doses of LTG provided protection against damage to the CA1 region of the hippocampus. Analogues of LTG of higher potency to block the release of glutamate may be necessary to ensure protection against ischemic brain damage.
 ...
PMID:Neurochemical and behavioral aspects of lamotrigine. 168 39

The effects of the calcium channel blocker nimodipine and the non-competitive NMDA-antagonists MK-801 and phencyclidine (PCP) on infarct size 48 h after occlusion of the middle cerebral artery (MCA-O) were evaluated in the rat. Nimodipine was given at a dose of 0.3 mg/kg s.c. 30 min prior and 8, 16, and 24 h after MCA-O. MK-801 (1 mg/kg i.p. or 10 mg/kg i.p.) or PCP (0.3, 1.0, 3.0, 10, or 30 mg/kg i.p.) were administered 30 min prior to ischemia. In additional experiments 30 mg/kg PCP was given 1, 3, or 5 h post ischemia. Nimodipine and 1 mg/kg MK-801 reduced cortical infarct volumes significantly by 50% and 55%, respectively, while cortical infarct size fell by 32% and total infarct volume was not altered significantly after administration of 10 mg/kg MK-801. Pretreatment with 10 or 30 mg/kg PCP reduced cortical infarction by 47-53% and total infarct volumes by 39-42%. Posttreatment with PCP was effective if started at 1 or 3 h post ischemia.
 ...
PMID:The effects of dizocilpine (MK-801), phencyclidine, and nimodipine on infarct size 48 h after middle cerebral artery occlusion in the rat. 191 95

The effects of non-competitive N-methyl-D-aspartate receptor antagonists on amnesia induced by carbon monoxide (CO) were investigated, since they have neuroprotective effects on delayed degeneration induced by ischemia. In the mice exposed to CO, acute and delayed amnesia were induced. (+)-MK-801 and (-)-MK-801 improved the delayed amnesia, but the effects of phencyclidine (PCP) were weak. (+)-MK-801 and PCP potentiated the acute amnesia. From these results, it is suggested that there is a stereoselectivity in the effects of MK-801 on CO-induced amnesia and that CO-induced delayed amnesia animals could be used as an ischemic amnesia model.
 ...
PMID:MK-801 ameliorates delayed amnesia, but potentiates acute amnesia induced by CO. 215 27

Transient brain ischemia results in a selective destruction of cell bodies within the hippocampus and cortex. This cellular destruction appears to be mediated through a release of endogenous exictatory amino acids following the ischemic episode, since the neurotoxic effects of ischemia can be attenuated by compounds that have antagonist activity at N-methyl-D-aspartate (NMDA) receptors. In the present study, the protective effects of a novel NMDA receptor antagonist, CGS 19755, were further evaluated by using quantitative autoradiography to characterize adenosine A1, NMDA, PCP, and benzodiazepine receptors in ischemic gerbil brain. Bilateral carotid artery occlusion (20 minutes) resulted in marked decreases (30-60%) in adenosine A1, NMDA, and PCP, but not benzodiazepine, receptors in gerbil forebrain. Postischemic treatment with CGS 19755 was found to completely block the ischemia-induced decreases in brain adenosine and NMDA receptors. [3H]TCP binding in ischemic gerbil brain was also elevated by CGS 19755 treatment; significant differences remained, however, between the CGS 19755-treated and control gerbils. These results indicate that transient brain ischemia produces significant and selective alterations in gerbil forebrain receptor systems. The observed decreases in radioligand binding are probably reflective of an ischemia-induced destruction of forebrain structures. However, there is some evidence that transient ischemia can also cause long-term changes in the affinity of some receptor systems. The postischemic efficacy of CGS 19755 appears to be due to its ability to block the neurotoxic effects of transient ischemia.
 ...
PMID:The novel N-methyl-D-aspartate (NMDA) antagonist CGS 19755 prevents ischemia-induced reductions of adenosine A1, NMDA, and PCP receptors in gerbil brain. 285 Jun 32

In this report the effects of phencyclidine (PCP) on physiologic variables, local cerebral blood flow (LCBF), and on hippocampal cell damage were measured in a rat model of forebrain ischemia (2-vessel occlusion and hypotension). Ischemia was induced for 10 min. LCBF was determined after 2 min of recirculation, using the [14C]iodoantipyrine technique. Hippocampal cell loss was quantified histologically 7 days postischemia as the percentage of acidic stainable neurons. Intravenous application of PCP (2 mg/kg) at 15 min prior to ischemia left postischemic LCBF unchanged, but neuronal damage was significantly reduced in hippocampal CA1 sector from 46 to 15.7%. PCP is concluded to reduce ischemic damage of neurons mainly via a direct effect on brain tissue.
 ...
PMID:Phencyclidine reduces postischemic neuronal necrosis in rat hippocampus without changing blood flow. 318 70

Although barbiturates are often effective as therapeutic agents in several types of brain ischemia, there is no consensus as to their mechanisms of action. Exactly why other intravenous anesthetics such as ketamine are not effective therapies in brain ischemia is not known. Structural analogs of ketamine such as phencyclidine (PCP) not only exert potent hallucinogenic properties and are widely abused drugs, but often result in hypertensive encephalopathies and death. In view of the paucity of information on the cerebral circulatory actions of barbiturates, ketamine and PCP (and analogs), in-vivo (microcirculatory) and in-vitro studies were undertaken. Barbiturates, in anesthetic concentrations (e.g., 10(-5) to 10(-4) M), were found to exert direct vasodilator actions on cerebral arterial smooth muscle; these relaxant actions appear to be related to inhibition of calcium ion (Ca2+) influx in cerebral vessels. The latter may be important in the salutory actions of barbiturates in brain ischemia, head trauma and cerebrovasospasm. Unlike barbiturates, ketamine was found to exert spasmogenic actions on cerebral arteries, which may aid in explaining the inability of this anesthetic to be of therapeutic value in brain ischemia. PCP and its analogs, as well as other hallucinogenic molecules (e.g., LSD, mescaline) produced spasms in cerebral arterioles, venules and arteries in concentrations which mimic their hallucinogenic potencies. Distinct PCP-like receptors which subserve contraction appear to exist on large as well as microscopic cerebral blood vessels. Spasms induced by PCP, its analogs and ketamine can be readily reversed or prevented completely by calcium channel blockers. The latter agents could be quite useful, clinically, in prevention of cerebral infarction, hypertension and fatality associated with PCP (and analogs) intoxication.
 ...
PMID:Effects of barbiturates, phencyclidine, ketamine and analogs on cerebral circulation and cerebrovascular muscle. 640 Apr 29

The purpose of the study was to test the hypothesis that the postischemic neuronal damage is accompanied by changes of the electrocorticogram (ECoG) of freely moving rats during long-term recovery after forebrain ischemia. Ten minutes forebrain ischemia was induced in male Wistar rats. ECoG was recorded 1 day before as well as 1 h, 1 day and 7 days after ischemia. The ECoG power was calculated and for characterizing postischemic ECoG development the percentage of preischemic ECoG power was evaluated. The awake state of the rats was considered for analysis only. Furthermore, the neuroprotective effect of phencyclidine (PCP, 5 mg/kg i.v., 15 min prior to ischemia) was demonstrated in the ECoG changes. One hour after ischemia the ECoG power of the theta (4.75-6.75 Hz), alpha (7.00-12.50 Hz) and beta (12.75-18.50 Hz) band was decreased compared with sham-operated controls and PCP did not influence these changes. However, 1 day after ischemia ECoG power of the saline-treated ischemic rats was completely restored and no longer different from that of the sham-operated group. PCP-treated ischemic animals showed significantly elevated ECoG power in comparison with saline-treated animals. Seven days after ischemia ECoG power of the saline-treated ischemic rats again decreased. In comparison with the ischemic controls, the ECoG activity of the PCP-treated ischemic rats was significantly higher. PCP maintained postischemic ECoG power at the non-ischemic control level. It is suggested that the decrease in the ECoG activity several days after ischemia is related to the delayed neuronal damage.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Quantitative analysis of the electrocorticogram after forebrain ischemia in the rat. 779 10

Substantiating evidence has raised the possibility that sigma ligands may have therapeutic potential as neuroprotective agents in brain ischemia. It has been suggested that the neuroprotective capacity of sigma ligands is related primarily to their affinity for the NMDA receptor complex and not to any selective action at the sigma binding site. However, sigma specific ligands, devoid of significant affinity for the NMDA receptor, are also neuroprotective via an inhibition of the ischemic-induced presynaptic release of excitotoxic amino acids. In the present study, we have investigated the potential neuroprotective effect of a comprehensive series of sigma ligands, with either significant (sigma/PCP) or negligible (sigma) affinity for the PCP site of the NMDA receptor, in order to delineate a selective sigma site-dependent neuroprotective effect. For this aim, we have employed two different neuronal culture toxicity paradigms implicating either postsynaptic-mediated neurotoxicity, (brief exposure of cultures to a low concentration of NMDA or Kainate) or pre- and postsynaptic mechanisms (exposure to hypoxic/hypoglycemic conditions). Only sigma ligands with affinity for the NMDA receptor [(+) and (-) cyclazocine, (+) pentazocine, (+) SKF-10047, ifenprodil and haloperidol] were capable of attenuating NMDA-induced toxicity whereas the sigma [(+)BMY-14802, DTG, JO1784, JO1783, and (+)3-PPP] and kappa-opioid [CI-977, U-50488H] ligands, with very low affinity for the NMDA receptor, were inactive. The rank order of potency, based on the 50% protective concentration (PC50) value, of sigma/PCP ligands against NMDA-mediated neurotoxicity correlates with their affinity for the PCP site of the NMDA receptor, and not with their affinity for the sigma site. In addition sigma/PCP, sigma or kappa-opioid ligands failed to attenuate kainate-mediated neurotoxicity. On the other hand, sigma/PCP, sigma and kappa-opioid ligands were potent inhibitors of hypoxia/hypoglycemia-induced neurotoxicity, although their neuroprotective potency did not correlate with their affinity for either the sigma or PCP binding sites. In conclusion, the ability of sigma and kappa-opioid ligands to attenuate hypoxia/hypoglycemia, but not NMDA or kainate-induced toxicity, suggests that these drugs exert their neuroprotective role by a predominantly presynaptic mechanism possibly by inhibiting ischemic-mediated glutamate release.
 ...
PMID:Distinct neuroprotective profiles for sigma ligands against N-methyl-D-aspartate (NMDA), and hypoxia-mediated neurotoxicity in neuronal culture toxicity studies. 779 19


1 2 Next >>