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)

If good anesthesia is to be provided to the patient undergoing surgery for an expanding intracranial lesion, certain principles should be borne in mind. These principles include: 1. Careful preoperative assessment of the patient 2. Awareness of abnormal intracranial dynamics in the presence of an intracranial mass lesion 3. The importance of a smooth induction of anesthesia 4. Adequate depth of anesthesia and complete muscle paralysis before laryngoscopy and intubation 5. The choice of a maintenance technique that does not increase ICP and allows adequate CPP. Failure to adhere to these principles may lead to sudden increases in intracranial pressure, decreased cerebral perfusion pressure, and regional ischemia. In the closed skull, internal herniation of brain tissue through the tentorial notch or the foramen magnum may occur. External brain herniation, with increased bleeding and rupture of cerebral cortex, may occur after the dura mater has been opened if these anesthetic parameters are not controlled. Neuroanesthesia, therefore, plays an important role in the reduction of morbidity and mortality in the surgery of intracranial lesions of all types, including neoplasms - not only in the operating room, but also in the pre- and postoperative care of the neurosurgical patient.
 ...
PMID:Anesthesia for intracranial surgery with particular reference to surgery for neoplasms. 77 21

Brief (5 min) bilateral carotid occlusion in the gerbil produces forebrain ischemia resulting, as previously reported, in almost complete neuronal loss in the CA1 region of the hippocampus; this neuronal destruction occurs between the 4th and 7th day post-ischemia. Various hippocampal biochemical indices were measured from just after such ischemia to 21 days of recirculation, and the temporal pattern of changes compared with that of cell loss. The level of thiobarbiturate reacting substances (TBARS), a measure of lipid peroxidation, was greatly elevated at 30 min after ischemia, rapidly returned to normal levels (by 60 min), but was again elevated on days 4-14. The beginning of this second period of elevation correlated closely with the onset of neuronal loss and the very abrupt and large (to about 32%) decrease in specific N-methyl-D-aspartate (NMDA) binding sites, measured with radioactive CPP. The number of muscarinic binding sites, measured with radioactive quinuclidinyl benzilate, showed an even greater decrease (to 13%) at 21 days post-ischemia, but the decrease was delayed (starting at day 7) and much more gradual than the loss in NMDA binding. In neither case was there any change in binding affinity at any time studied. Acetylcholine (ACh) concentrations were initially greatly decreased (to about 15% at 5 min), transiently increased (to about 130% at 30 min), and then decreased again (to about 15% at 60 min), after which gradual recovery occurred and was completed by day 14. Since no inhibition of choline acetyltransferase activity was observed at any time, the reversible depression in ACh must depend upon some factor other than loss of this key synthetic enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Time course of changes in lipid peroxidation, pre- and postsynaptic cholinergic indices, NMDA receptor binding and neuronal death in the gerbil hippocampus following transient ischemia. 182 14

Ischaemia results in elevated extracellular glutamate concentrations, and drugs which act at the N-methyl-D-aspartate sub-type of glutamate receptor have been shown to decrease ischaemic brain damage. Because almost all patients who die after severe head injury demonstrate ischaemic brain damage, and acute subdural haematoma (ASDH) is one of the commonest complications of severe head injury, we have studied this condition in a rat model. Using double-label autoradiography, we have measured the effects of ASDH on cerebral glucose utilization and cerebral blood flow (RCBF). Following ASDH, increased glucose utilisation was observed in some cortical and hippocampal structures, without concomitant increases in blood flow. Directly below the ASDH, blood flow and glucose utilization were profoundly reduced. Pre-treatment with D-CPP-ene, a competitive NMDA antagonist, resulted in amelioration of hypermetabolism induced by the ASDH. The results suggest that NMDA antagonists may prevent ischaemic brain damage after ASDH by reducing hypermetabolism, induced by glutamatergic mechanisms.
 ...
PMID:Ischaemic brain damage associated with tissue hypermetabolism in acute subdural haematoma: reduction by a glutamate antagonist. 198 82

We have administered antagonists acting competitively or noncompetitively at the N-methyl-D-aspartate receptor after a short period of incomplete ischaemia and evaluated selective neuronal loss in the CA1 region of the rat hippocampus. The competitive antagonists D-(-)-2-amino-7-phosphonoheptanoate (2APH); 100 or 330 mg/kg; 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP); 3.3 or 10 mg/kg; and CGS 19755 (cis-4-phosphonomethyl-2-piperidine carboxylate) 3.3 or 10 mg/kg; and the noncompetitive antagonists MK801 [+)5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), 0.3, 1, or 3 mg/kg, and dextrorphan, 2, 6, 18, or 54 mg/kg, were administered intraperitoneally 15 min and 5 h after a 10-min incomplete ischaemia period; additionally MK801 (1 or 3 mg/kg) and CGS 19755 (10 or 30 mg/kg) were administered 5 and 10 h postischaemia. Seven days after ischaemia, the brains were fixed by perfusion. CA1 pyramidal cell counts were performed on Nissl-stained sections using an ocular grid piece. Ventilated (no ischaemia) control animals had a mean of 406 +/- 13 CA1 neurones/3 grid lengths. Ischaemia reduced this mean to 157 +/- 23. A significant protective effect against this cell loss was seen after two injections (at 15 min and 5 h postischaemia) of 2APH, CPP (10 mg/kg), CGS 19755 (10 mg/kg), MK801 (1 mg/kg), and dextrophan (54 mg/kg). Delayed injection (5 and 10 h postischaemia) of CGS 19755 (10 and 30 mg/kg) and MK801 (1 and 3 mg/kg) did not provide any protection against pyramidal cell loss.
 ...
PMID:Protection by NMDA antagonists against selective cell loss following transient ischaemia. 215 99

The influence of transient forebrain ischemia on the temporal alteration of glutamate receptors in the hippocampal formation was analyzed by means of in vitro quantitative receptor autoradiography. We compared the binding of N-methyl-D-aspartate (NMDA) receptors using [3H]3-[+/-)2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), noncompetitive NMDA antagonist binding sites using [3H]N-(1-(2-thienyl)-cyclohexyl)-3,4-piperidine (TCP), and kainate (KA) receptors. In the CA1 subfield of the hippocampus, the number of NMDA receptors and noncompetitive NMDA antagonist binding sites remained constant during the early stage of recirculation when the CA1 pyramidal cells remained histologically intact. A significant reduction of these receptor densities was observed 7 days following ischemia, when NMDA receptors and noncompetitive NMDA antagonist binding sites lost 64 and 29% of their binding sites in the stratum radiatum of the CA1, respectively. The KA receptor density in the CA1 subfield decreased by 44% 7 days after ischemia. Marked loss of the above-mentioned receptors in the CA1 after selective depletion of the CA1 pyramidal cells indicated that NMDA receptors, noncompetitive NMDA antagonist binding sites, and KA receptors in the CA1 are predominantly localized on the CA1 pyramidal cells. NMDA receptor density in the CA3 gradually decreased during the recirculation period. The stratum moleculare of the dentate gyrus, whose structure was histologically intact after ischemic insult, also showed a reduction of NMDA receptors 7 days following ischemia. [3H]KA receptor density in the stratum lucidum of the CA3 and in the hilus also decreased during recirculation. These
 ...
PMID:Excitatory amino acid binding sites in the rat hippocampus after transient forebrain ischemia. 255 Apr 93

A large, extracellular negative DC shift, termed epileptic depolarization, could be elicited during zero magnesium-induced epileptic activity in the rat hippocampal slice. In 10 mM glucose medium, epileptic depolarization was elicited by high-frequency synaptic stimulation. During epileptic depolarization synaptic responses were abolished, but recovered in 10.4 +/- 2.1 min. In low glucose (2 mM) medium, epileptic depolarization either occurred spontaneously or could be elicited by high frequency synaptic stimulation, and no recovery of synaptic responses was observed for at least 30 min. This long-term synaptic failure was blocked by the competitive NMDA antagonists, 3-[+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP, 100 microM) and D-2-amino-7-phosphonoheptanoate (D-AP7, 100 microM) when added at the peak of epileptic depolarization, but not 5 min afterwards. Intracellular analysis showed that this extracellular DC shift was correlated with a membrane depolarization which approached 0 mV. With 10 mM glucose medium, the membrane potential returned to resting level in 6.3 +/- 1.9 min. In 2 mM glucose medium, neurons remained depolarized and no recovery was observed. This persistent depolarization could account for the loss of synaptic function recorded extracellularly. Application of 100 microM CPP blocked persistent depolarization and allowed for the recovery of the membrane potential. Epileptic depolarization was also observed during picrotoxin-induced epileptic activity. Both anoxic depolarization during experimental ischemia and epileptic depolarization can trigger long-term synaptic failure and persistent depolarization. Epileptic depolarization and anoxic depolarization may be triggers which can lead to neuronal failure in diseases associated with neuronal degeneration.
 ...
PMID:Epileptiform activity in vitro can produce long-term synaptic failure and persistent neuronal depolarization. 255 58

CPP reflects perfusion problems related to increased ICP or inadequate MAP. CPP is a most helpful and practical management tool. The relationship of CBF and CPP depends on cerebral vascular resistance (flow equals pressure divided by resistance). At present, we do not have a practical method to measure vascular resistance or CBV. A close relationship between an increase in CBV and increase in ICP exists. However, the relationship between CBF and ICP is more complex. Whereas CBV is strongly dependent on vasodilation and venous return, CBF is influenced by CPP, vascular resistance, viscosity changes, and focally or diffusely increased ICP. For instance, in hypotensive shock one finds a low CBF with an elevated CBV (and ICP) from vasodilation related to hypercapnia, anoxia, or acidosis. Nevertheless, about two thirds of patients with increased ICP after head injury have increased CBF (hyperemia) and increased CBV. This frequent hyperemia is one rationale for the wide usage of hyperventilation to treat increased ICP. It must be recognized that a group of patients may have ischemia caused by excessive hyperventilation therapy for increased ICP. The PaCO2 must not be allowed to decrease to 20 mmHg or lower, but in some patients a PaCO2 level of 21 to 25 may be predisposing to ischemia. Strong consideration is thus given to monitoring CBF and cerebral oxygen metabolism (arteriovenous oxygen content difference [AVDO2], CMRO2) in states of coma and increased ICP. In such patients, continuous infusion of mannitol may result in improved CBF, and hyperventilation therapy can be less aggressive.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Nonsurgical management of increased intracranial pressure. 270 May 10

Effects of nipradilol on hemodynamics and transmural energy metabolism of underperfused (ischemic) canine hearts were investigated. The ischemic heart was prepared by constricting a tube connecting the circumflex coronary artery with the carotid artery for 10 min so that the perfusion pressure (CPP) was reduced to 30 mmHg. The reduction in CPP resulted in decreases in coronary blood flow (CBF) by 70%, regional myocardial contractile force (MCF) by 30%, myocardial ATP contents by 32% (inner layer)-22% (outer) and creatine phosphate by 75% (inner)-60% (outer). Increases in the left ventricular end diastolic pressure (LVEDP) by 4.8 mmHg, myocardial inorganic phosphate contents by 1.9 times (inner)-1.3 (outer) and lactate by 4.3 times (inner)-2.4 (outer) were also observed. In dogs with normal hearts, an infusion of nipradilol (10 micrograms/kg/min, i.v., for 15 min) decreased CPP by 25%, CBF by 40%, cardiac effort index by 45% and MCF by 30 to 40%, and it slightly increased LVEDP without affecting myocardial high-energy phosphate and lactate levels. In ischemic hearts, nipradilol infusion starting 5 min before ischemia attenuated the ischemia-induced elevation of LVEDP to 1.8 mmHg, and the ischemia-induced changes in high-energy phosphate contents to 1/2 (inner)-1/3 (outer) and changes in lactate to 1/6 (inner)-1/10 (outer). These results indicate that nipradilol improves the ischemic derangement of both transmural energy metabolism and hemodynamics.
 ...
PMID:Effects of nipradilol, a new beta-adrenoceptor blocking agent with vasodilating properties, on transmural energy metabolism in the underperfused canine heart. 288 16

N-Methyl-D-aspartate (NMDA) antagonists reduce ischemic brain damage and associated hypermotility. Two potent, selective and competitive NMDA antagonists, cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS 19755) and 4-(3-phosphonopropyl)-2-piperazine-carboxylic acid (CPP), were characterized in the gerbil ischemia model with respect to dose-response and time course effects. Both drugs were effective in reducing ischemia-induced hippocampal brain damage as well as hypermotility. In this model, CGS 19755 was more potent than CPP, and had protective effects when given after longer delays between ischemia and drug administration.
 ...
PMID:The N-methyl-D-aspartate antagonists CGS 19755 and CPP reduce ischemic brain damage in gerbils. 328 58

In the present study, spontaneous and evoked release of selected amino acids in the rat spinal cord was studied using in vivo microdialysis. Perfusion of the microdialysis probe with 100 K+ evoked a 2-4-fold increase in release of the putative neurotransmitters aspartate, glutamate and taurine while glutamine was decreased. K(+)-evoked release of glutamate was almost completely Ca(2+)-dependent while that of aspartate was partially Ca(2+)-dependent. Taurine release was not affected by substituting Ca2+ with Co2+. Perfusion with 5 mM N-methyl-D-aspartate (NMDA) evoked 3-9-fold release of glutamate, glycine and taurine and a small increase in extracellular beta-alanine. No significant changes in glutamine and serine were found. 5 mM of the competitive NMDA antagonist 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) reduced NMDA-evoked release of glutamate and taurine by approx. 50%. 5 mM 3-amino-1-hydroxypyrrolid-2-one (HA-966), an agonist at the glycine site of the NMDA receptor with very low efficacy, completely inhibited NMDA-evoked release of taurine and reduced the levels of released glutamate below baseline, similar to the effect of 1 mM CPP alone. The present results show that in situations of excessive release of excitatory amino acids such as spinal ischemia and trauma. NMDA receptor-evoked release of glutamate may amplify the deleterious process and spread the damage.
 ...
PMID:In vivo studies on NMDA-evoked release of amino acids in the rat spinal cord. 758 Aug 74


1 2 3 4 Next >>