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PubMed1991

[Usefulness and limitations of stress 201-thallium myocardial imaging in patients with Kawasaki disease].

Thallium-201 myocardial imaging was performed in 150 patients with a history of Kawasaki disease, aged 6 months to 16 years old. Forty-five patients were studied with ergometer exercise and 105 patients had dipyridamole administration. The findings of thallium imaging were compared with those of coronary angiography. Seventy-two cases with severe coronary stenosis (over 75%) were classified in 3 groups; 13 with the left anterior descending artery lesion, 31 with only the right coronary artery lesion and 28 with multi-vessel involvement. In 72 cases with severe coronary stenosis, the sensitivity of thallium imaging for detecting coronary stenotic lesions was 85%, 74% and 67% in the 3 groups, respectively. In 78 cases without severe coronary stenosis, 5 cases (6%) had persistent perfusion defects on thallium imaging, 3 of which were associated with dyskinesis of the left ventricle documented by cineangiography. They were considered to have damaged myocardium probably due to peripheral myocardial infarction or myocarditic problems. Thallium-201 myocardial imaging was proved to be a useful method to detect coronary stenosis, however its sensitivity for detecting lesions of the right coronary artery or multi-vessels was relatively low. This may be attributable to a significantly higher incidence of segmental stenosis (recanalization) with sufficient coronary flow and multiple coronary collateral vessels in patients with such lesions.

Adolescent↗
PubMed1991

Specific monosynaptic sensory-motor connections form in the absence of patterned neural activity and motoneuronal cell death.

The importance of neural activity and motoneuronal cell death in the formation of specific synaptic connections between muscle afferents and motoneurons was studied in chick embryos. Patterned neural activity was blocked by applying d-tubocurarine (dtc) chronically to embryos during the period when sensory-motor connections are formed [stages (St) 28-42]. Dtc blocks neurogenic muscle contractions, thereby abolishing any temporal correlation between neural activity in motoneurons and stretch-sensitive afferents. The normal pattern of motoneuronal bursting is also blocked (Landmesser and Szente, 1986), as is motoneuronal cell death (Pittman and Oppenheim, 1979). Dtc applications were started more than 1 d before muscle sensory afferent collaterals make anatomical contact with motoneuronal dendrites and continued until St 38-42, when the pattern of synaptic connectivity was examined by recording synaptic potentials intracellularly from identified lumbosacral motoneurons upon stimulation of identified populations of muscle afferents. In both normal and dtc-treated animals, large monosynaptic excitatory potentials were evoked in homonymous motoneurons (those that supply the same muscle as the sensory afferents) and were often observed in motoneurons that supplied synergistic muscles. Monosynaptic potentials were uncommon in motoneurons supplying antagonistic muscles. The overt patterns of sensory-motor connections in normal and dtc-treated embryos were essentially identical. However, the amplitudes of the composite EPSPs recorded in dtc-treated animals were consistently about twice as large as normal. These observations suggest that neither normal patterns of neuronal activity nor motoneuronal cell death play a large role in determining the specificity of connections between the sensory and motor neurons involved in the stretch reflex.

Afferent Pathways↗
PubMed1992

Collateral resistance to photon and neutron irradiation is associated with acquired cis-platinum resistance in human ovarian tumour cells.

The melphalan resistant variant of the human ovarian OAW42 tumour cell line has previously been shown to be collaterally resistant to photon irradiation, but not to fast neutrons. In the present study, the "in vitro" photon and neutron radiosensitivity of human ovarian OAW42 tumour cells with acquired resistance to cis-platinum has been studied, to determine whether a similar pattern of cross-resistance exists between cis-platinum and these ionising radiations. Analysis of SF2 values suggests that resistance to cis-platinum conferred a 3-fold decrease in sensitivity to photons, primarily attributable to a 5-fold decrease in the magnitude of the initial slope (alpha). Depletion of GSH by BSO restored the magnitude of alpha to a value similar to that of the parental line. However, cis-platinum resistant OAW42/CP cells, in contrast to melphalan resistant cells, were 1.5-fold more resistant to "fast" neutrons (assessed at D0.1 survival level) than the parental OAW42 cell line. The mechanism for the collateral resistance between cis-platinum, and both photons and neutrons remains to be determined, but although GSH levels may be directly, or indirectly involved in the collateral resistance to photons, they would appear not to involved with the mechanisms responsible for collateral neutron resistance, in the cis-platinum resistant human ovarian cell lines used in this study.

Cell Survival↗
PubMed1989

Parametric imaging in cerebral radionuclide angiography (RNA) by planar imaging improving presentation and objectivation of cerebral blood flow.

Methods of parametric imaging of radionuclide angiography using parameters like appearance time, peak time, transit time, height of peak, arterial slope and area of inflow were developed and evaluated regarding their diagnostic meaning in 111 patients suffering from TIA or PRIND and in 30 normal persons. The meaning of these single parameters could shown depended on the specificity of the diagnostic question. Local cerebral blood flow can be estimated most favourably by parametric images of area of inflow whereas transit time is most promising as a diagnostic tool for evaluation of total cerebral blood flow classified with reference to severity of the perfusion disturbance. Appearance time is suited very well to estimation of collateral perfusion. Blood flow in great cerebral arteries could be seen well by non parametric imaging of radioactivity inflow in the brain supplying arterial vessels in the cranial floor. Applying a combination of the parametric images, the sensitivity for detection of disturbances of cerebral blood flow amounts to 0.91. A specificity of 0.88 and accuracy of 0.90 were found. The described combination of evaluation of RNA using various parameters is considered a well suited method for detection of disturbances in local and total cerebral blood flow by means of planar imaging.

Cerebral Arterial Diseases↗
PubMed1989

Baclofen induces spontaneous, rhythmic sharp waves in the rat hippocampal slice.

In rat hippocampal slices, low concentrations of (+/-) baclofen (0.1 to 1.5 microM) elicited spontaneous, rhythmic sharp waves (SRSWs). These low amplitude (0.1 to 0.3 mV) SRSWs were visible with high amplification in the extracellular recordings from the CA1, CA2, and CA3 regions and were roughly synchronous in all areas. SRSW amplitude increased and frequency decreased as baclofen concentration increased up to 1.5 microM, but SRSWs were suppressed at concentrations of 5 microM and higher. The amplitude of the SRSWs was greater in the strata radiatum and the lacunosum moleculare than in the stratum pyramidale. (-)-Baclofen was much more potent in eliciting SRSWs than (+)-baclofen. Low concentrations of baclofen also caused the extracellular excitatory postsynaptic potential in the stratum radiatum of CA3b evoked by stimulation of the Schaffer collaterals to broaden and develop a secondary peak. Slices pretreated with pertussis toxin required much higher concentrations of baclofen to elicit the SRSWs, indicating that the baclofen may be eliciting the SRSWs through a G protein-sensitive mechanism. Baclofen has both inhibitory and disinhibitory effects on neurons. The appearance of these spontaneous population events suggests that, at low concentrations, the disinhibitory effects may be more powerful than the inhibitory effects.

Action Potentials↗
PubMed2006

Effects of monomethyltin and dimethyltin compounds on heterologously expressed neuronal ion channels (Xenopus oocytes) and synaptic transmission (hippocampal slices).

The aim of this study was to investigate the effects of monomethyltin trichloride (MMT) and dimethyltin dichloride (DMT) on various neuronal ion channels heterologously expressed in Xenopus oocytes and on synaptic transmission in hippocampal slices of young (14-21 days old) and adult (2-4 months old) rats. The Xenopus oocyte expression system was chosen to allow direct assessment of the effects of MMT and DMT both on glutamate receptors sensitive to AMPA and NMDA and on various voltage-operated potassium and sodium channels. Hippocampal slices were used to analyze the effects of MMT and DMT on synaptic potentials generated by the important excitatory Schaffer collateral-CA1 synapse. In general, MMT and DMT were found to have no effect either on voltage-operated sodium and potassium channels or on the metabotropic glutamate receptor but they did differentially affect the functions of ionotropic glutamate receptors and glutamatergic synaptic transmission. MMT (100 microM) significantly reduced NMDA-mediated ion currents by up to 32%, but had no effect on ion currents through AMPA receptors. In slices of adult rats, MMT had no effect on the amplitudes of evoked fEPSPs and brought about a 35% reduction in the LTP amplitudes. In contrast, in slices of young rats MMT evoked a reversible 30% increase in the amplitudes of fEPSPs but had no effect on LTP induction. DMT (100 microM) reduced ion currents through NMDA-receptor ion channels by up to 29% and those through AMPA-receptor ion channels by up to 7%. In hippocampal slices 100 microM DMT reduced the amplitudes of fEPSPs (adults: 50%; young rats: 70%) and LTP (adults: 40%; young rats: 55%). Neither of the organotins affected the paired-pulse facilitation at this synapse, indicating that the organotins exert their effects at the postsynaptic site. The action of MMT and DMT may contribute to the organotin-induced impairment of behavior patterns in connection with learning and memory.

Animals↗
PubMed1999

Diagnostic value of connective tissue metabolites in Schistosoma mansoni related liver disease.

Reliable non-invasive markers of hepatosplenic involvement in schistosomiasis are needed for determination of morbidity levels in endemic populations and for diagnosis and follow-up of affected individuals. Serum levels of connective tissue metabolites have been investigated as fibrosis markers in various hepatic disorders, but their accuracy in the detection of hepatosplenic schistosomiasis under endemic conditions has not been fully elucidated. 206 adult inhabitants of a Tanzanian village highly endemic for schistosomiasis mansoni (prevalence 88%) underwent clinical, parasitological and sonographic work-up; sera were tested for aminoterminal procollagen III-peptide (PIIIP), carboxyterminal procollagen IV peptide (NC1) and laminin. Connective tissue marker levels did not correlate with the presence or intensity of infection. NC1 levels were significantly correlated with periportal liver fibrosis (P < 0.001), splenomegaly (P < 0.002), portal vein dilatation (P < 0.004) and the presence of portosystemic collaterals (P < 0.001); for PIIIP and laminin, none of the respective relationships was significant. Due to wide overlap of NC1 levels between individuals with normal sonography findings and those with advanced periportal fibrosis and portal hypertension, the sensitivity and positive predictive value of this markers to detect these individuals were low (< 40%), although specificity and overall accuracy in the given setting were good (80-90%). It is concluded that PIIIP and laminin are not useful as diagnostic serum markers of hepatosplenic schistosomiasis at the community level; NC1 was significantly related to various indices of hepatosplenic involvement, but its low sensitivity precludes its use as a screening tool under endemic conditions.

Adolescent↗
PubMed1994

The effect of kainic acid on the release of GABA in rat neostriatum and substantia nigra.

In order to test the hypotheses that stimulation of non-N-methyl-D-aspartate (NMDA) receptors in the neostriatum causes the release of gamma-aminobutyric acid (GABA) from nigrostriatal neurones, dual microdialysis was carried out in the neostriatum and substantia nigra of freely moving rats. Application of kainic acid to the neostriatum caused a dose-dependent release of GABA both locally and, at the same time, from the ipsilateral substantia nigra. These effects were blocked by the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX). Direct application of kainic acid to the substantia nigra caused a DNQX-sensitive local release of GABA. It is concluded that excitatory amino acid receptor stimulation of the neostriatum releases GABA from striatonigral neurones and that stimulation of the substantia nigra causes the release from striatonigral terminals and/or the collaterals of nigrofugal neurones.

Animals↗
PubMed2004

Involvement of a glutamergic mechanism in gamma-dendrotoxin-induced hippocampal neuronal cell loss in the rat.

The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticeps, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats pretreated with CGP040116, a N-methyl-D-aspartate (NMDA) receptor antagonist, and in rats bearing a monolateral surgical lesion of the Schaffer collaterals whose terminals originate from CA3 pyramids and release glutamate in the CA1 hippocampal area. Administration of 35 pmol gamma-dendrotoxin elicited in all of the treated animals (n=8) bilateral EEG discharges and damage to the hippocampal formation. Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1, CA3 and CA4 pyramidal cell layers. The lowest dose (0.35 pmol; n=4) of the toxin used did not affect EEG activity and failed to cause significant hippocampal cell loss whereas the 3.5 pmol (n=6) dose caused EEG seizures and hippocampal cell loss limited to the CA1 area. Systematic intraperitoneal administration of CGP040116 (5mg/kg given 30 min. previously) delayed the onset of EEG seizures and reduced the number of epileptogenic discharges typically observed in rats receiving an injection of gamma-dendrotoxin (35 pmol) alone. Similarly, this treatment prevented the damage inflicted to the hippocampus by the toxin and in no instance was significant neuronal loss observed. Protection against seizures and hippocampal damage was also observed by a monolateral surgical lesion to the Schaffer collaterals. In conclusion, the present data suggest that an excitotoxic, glutamate-mediated, type of mechanism underlies seizures and hippocampal damage induced by gamma-dendrotoxin in rats.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

Improvement in contractility of infarct zone after dobutamine infusion predicts good (TIMI II or III) flow in infarct related artery.

Eighteen patients of 'Q' wave acute myocardial infarction (AMI) (age 50 +/- 6.2 years), underwent dobutamine stress echocardiography (DSE) before hospital discharge (7.2 +/- 1.3 days after AMI) to find out the correlation between response of infarct zone to dobutamine infusion and TIMI grade flow in infarct related artery (IRA). The aim of study was to test the hypothesis that infarct zone which shows improvement in contractility after dobutamine infusion has viable myocardial tissue and would have good flow (TIMI II or III) in IRA. Echocardiographically, improvement in contractility in the centre of infarct zone by at least 1 grade (on a scale of 4) was termed as positive response on DSE. The mean dose of dobutamine was 19.4 micrograms/kg/min. Ten patients had positive response on DSE; 8 of them had good antegrade flow in IRA. Eight patients had no improvement in contractility of infarct zone on DSE; 6 of them had poor flow in IRA. Clinical markers of reperfusion (relief of chest pain, early ST settlement, peak CPK-MB levels), age of patient, site of AMI, time to thrombolysis, resting left ventricular ejection fraction, wall motion score of the infarct zone and presence of collaterals were not significantly different in patients with good or poor flow in IRA. Thus, improvement in contractility of infarct zone after dobutamine infusion can predict good flow (TIMI II or III) in IRA with 80 percent sensitivity, 75 percent specificity, 80 percent diagnostic accuracy, 80 percent positive predictive value and 75 percent negative predictive value.

Adult↗
PubMed1998

Glial contribution to glutamate uptake at Schaffer collateral-commissural synapses in the hippocampus.

Astrocytes in the hippocampus express high-affinity glutamate transporters that are important for lowering the concentration of extracellular glutamate after release at excitatory synapses. These transporters exhibit a permeability to chaotropic anions that is associated with transport, allowing their activity to be monitored in cell-fee patches when highly permeant anions are present. Astrocyte glutamate transporters are highly temperature sensitive, because L-glutamate-activated, anion-potentiated transporter currents in outside-out patches from these cells exhibited larger amplitudes and faster kinetics at 36 degreesC than at 24 degreesC. The cycling rate of these transporters was estimated by using paired applications of either L-glutamate or D-aspartate to measure the time necessary for the peak of the transporter current to recover from the steady-state level. Transporter currents in patches recovered with a time constant of 11.6 msec at 36 degreesC, suggesting that either the turnover rate of native transporters is much faster than previously reported for expressed EAAT2 transporters or the efficiency of these transporters is very low. Synaptically activated transporter currents persisted in astrocytes at physiological temperatures, although no evidence of these currents was found in CA1 pyramidal neurons in response to afferent stimulation. L-glutamate-gated transporter currents were also not detected in outside-out patches from pyramidal neurons. These results are consistent with the hypothesis that astrocyte transporters are responsible for taking up the majority of glutamate released at Schaffer collateral-commissural synapses in the hippocampus.

ATP-Binding Cassette Transporters↗
PubMed2003

Ultrasonographically predicting the extent of collateral flow through superficial temporal artery-to-middle cerebral artery anastomosis.

BACKGROUND AND PURPOSE: This study was performed to elucidate whether the extent of bypass flow through superficial temporal artery-to-middle cerebral artery (STA-MCA) anastomosis could be indirectly estimated by measuring the blood flow velocity in the superficial temporal artery (STA) by using duplex ultrasonography. METHODS: We analyzed 29 patients (31 sides) who underwent STA-MCA bypass surgery for occlusive cerebrovascular disease (28 sides) or unclippable cerebral aneurysm that required therapeutic occlusion of the internal carotid artery (three sides). The flow velocities of the STA were measured by using ultrasonography. For patients who underwent the surgery unilaterally, the flow velocity ratios of the operated side to the contralateral side for the individual arteries were calculated. The correlation between these flow velocity parameters and the extent of bypass flow, which was graded based on the findings of cerebral angiography, was investigated. RESULTS: Both the affected STA flow velocity and the STA flow velocity ratio, particularly those in the end diastole, increased in patients with more extensive bypass flow. In patients with extensive, moderate, and poor bypass flow, the end diastolic flow velocities of the operated STA were 27.4 +/- 8.8, 23.0 +/- 7.8, and 13.5 +/- 7.5 cm/s, respectively and the end diastolic flow velocity ratios of the STA were 3.4 +/- 0.8, 2.1 +/- 0.5 and 1.3 +/- 0.4, respectively. The pulsatility index and resistance index of the affected STA were significantly lower in the patients with more extensive bypass flow. The optimal threshold value of the end diastolic flow velocity ratio of STA for the group with extensive bypass flow was 2.75, whereas that for the group with poor bypass flow was 1.60. With the obtained values, the sensitivity and specificity were 87.5% and 93.9% for the group with extensive bypass flow and 95.2% and 95.0% for the group with poor bypass flow, respectively. CONCLUSION: The blood flow velocity in the operated STA seems to be a highly sensitive parameter for predicting the extent of bypass flow in patients undergoing STA-MCA anastomosis.

Angiography, Digital Subtraction↗
PubMed1989

Effects of glucose deficiency on glutamate/aspartate release and excitatory synaptic responses in the hippocampal CA1 area in vitro.

The effects of glucose deficiency on (1) the K+-evoked release of glutamate and aspartate and (2) excitatory synaptic transmission were studied in the Schaffer collateral-commissural-ipsilateral associational (SCCIA) projection to area CA1 of the rat hippocampal formation in vitro. Compared with 1 or 10 mM glucose, superfusion of CA1 slices with 0.1 mM glucose enhanced the K+-evoked release of both glutamate and aspartate, increased the ratio of aspartate release to glutamate release and did not affect the release of GABA. With both high and low glucose concentrations, the K+-evoked release of glutamate and aspartate originated predominantly from a Ca2+-sensitive store associated with the SCCIA projection. Superfusion with glucose-deficient medium abolished the inhibitory effect of adenosine on glutamate and aspartate release, but augmented the enhancing effect of the adenosine antagonist 8-phenyltheophylline. These results suggest that enough endogenous adenosine was released from the slices under these conditions to saturate the presynaptic A1 receptors. Despite its facilitatory effect on excitatory transmitter release, glucose-deficient medium inhibited transmission at Schaffer collateral-commissural synapses. Even when the postsynaptic response to a single electrical pulse was abolished, however, a substantial response could still be evoked through paired-pulse or frequency potentiation and the inhibition promptly reversed upon superfusion with 10 mM glucose. The increased ratio of aspartate release to glutamate release appears to reflect changes in the tissue content of these amino acids. The enhanced release of both excitants is suggested to result partly from a rise in intraterminal Ca2+ concentration and partly from inhibition of glutamate/aspartate uptake. Enhanced aspartate release may be particularly relevant to hypoglycemic damage in the CA1 area, because aspartate is a more potent hippocampal excitotoxin than glutamate.

Animals↗
PubMed1987

Vertebral artery Doppler sonography.

We have examined the vertebral and subclavian arteries in 1,205 patients using directional continuous-wave (c-w) Doppler sonography, and compared the sonographic findings with the results of unilateral or bilateral retrograde brachial arteriographies in the same patients. Doppler sonography revealed 33 false positives among 909 cases with normal angiographic findings. Some types of vertebral artery (VA) lesions allowed an excellent, others a fairly good differentiation by Doppler sonography: the complete subclavian steal syndrome with constant reversal of VA flow was reliably detected (16 cases). In the incomplete steal syndrome (5 cases) sonography was superior to angiography. Two bilateral distal VA occlusions and seven basilar artery occlusions - six in the proximal third and one in the rostral third - were detected sonographically; four basilar occlusions sparing the caudal third and one case exhibiting rete mirabile anastomoses were not identified by Doppler sonography. Our acoustically defined sonographic criteria did not permit an unequivocal assignment to an anatomical variant or a vascular lesion. The sensitivity in the detection of a severe stenosis at the VA origin amounted to 16 out of 31, and to 12 of 25 in cases with a proximal VA occlusion and reconstitution of the distal VA through cervical collaterals. Our results confirm that the conventional hand-held c-w Doppler sonography cannot replace angiography in the evaluation of vertebro-basilar insufficiency. It rather serves as an aid to the decision for or against angiography, and in the follow-up of angiographically proven lesions. However, several therapeutically important lesions are readily diagnosed by sonography.

Angiography↗
PubMed1998

Segmental comparison between coronary angiography and positron emission tomography reveals low predictive value of epicardial flow for viability.

BACKGROUND: The functional significance of the anterograde and retrograde filling of coronaries on angiography is controversial. METHODS AND RESULTS: Eighteen patients with 27 severe lesions (> 85% diameter stenosis) after previous extensive myocardial infarction were selected. The left ventricle was divided into 33 segments for regional comparison of epicardial flow (as assessed by angiography) and tissue perfusion as well as metabolism (as measured by 13NH3- and 18FDG-PET). Viability was defined as normal perfusion (> 80% relative of maximum 13NH3 activity) or mismatch defect (> 1.2 metabolism/flow ratio). A method has been developed to register the 'lesion predicted region', determined on the basis of angiography, in the same polar map as derived from the positron emission tomography data. Distal to the lesion, the anterograde epicardial flow was evaluated by Thrombolysis in Myocardial Infarction (TIMI) criteria (TIMI flow 0-3), and retrograde filling was graded on a 0-3 scale (collateral grade 0-3). TIMI flow grade and retrograde collateral grade in every lesion predicted region segment were summed to indicate the total segmental epicardial flow. Out of the 594 segments, 369 were associated with a severe lesion. Among them, significantly higher average perfusion and metabolic activities were found in segments of good epicardial filling (summed epicardial flow > or = 3) than in the territories of limited epicardial flow (summed score < 3): 65.4 +/- 17% vs 45.6 +/- 10 (P = 0.001%) and 68.6 +/- 16% vs 47.4 +/- 11% (P = 0.0004), respectively. However, when we analysed the predictive value of angiographically detectable good epicardial flow for positron emission tomography viability criteria then the positive predictive value was found to be as low as 0.5, while the negative predictive value was considerably higher (0.82). CONCLUSION: After myocardial infarction, angiographically detectable limited epicardial flow reveals scarred segments while good epicardial contrast filling does not necessarily indicate maintenance of nutritive function.

Adult↗
PubMed1998

The effect of fentanyl on electrophysiologic recovery of CA 1 pyramidal cells from anoxia in the rat hippocampal slice.

UNLABELLED: Fentanyl is widely used in conditions in which the brain is at risk of ischemic or anoxic injury. We evaluated the effect of fentanyl on anoxic injury to CA 1 pyramidal cells in the rat hippocampus. These neurons are extremely sensitive to anoxic injury and are densely populated with opioid receptors. We prepared hippocampal slices from adult Sprague-Dawley rats and evoked a postsynaptic population spike in the CA 1 pyramidal cell region by stimulating the Schaffer collateral pathway. The amplitude of this response was used to evaluate the effect of fentanyl on anoxic injury. Pretreatment with fentanyl (50 or 500 ng/mL) did not alter the amplitude of the CA 1 population spike before anoxia, nor did it alter the recovery of this response after 5,6, or 7 min of anoxia. After 5 min of anoxia, the population spike recovered to 76% of its preanoxic level in the control group and to 87% in the group treated with 500 ng/mL of fentanyl. After 6 min of anoxia, recovery was 45% in the control group, 57% in the group treated with 50 ng/mL of fentanyl, and 58% in the group treated with 500 ng/mL of fentanyl. After 7 min of anoxia, recovery was 5% in the control group and 4% in the group treated with 50 ng/mL of fentanyl. We conclude that fentanyl does not affect the recovery of the electrophysiological response in rat hippocampal neurons subjected to an anoxic insult. IMPLICATIONS: Because fentanyl is used in large doses during surgical procedures in which the brain is at increased risk of ischemic or anoxic injury, it is important to determine its effect on such injury. Using the rat hippocampal slice model, we found fentanyl to be neither neurotoxic nor protective against anoxic injury to neurons when used in concentrations comparable to those produced in clinical practice.

Analgesics, Opioid↗
PubMed1989

Absence of P2-purinoceptors in hippocampal pathways.

1. Many apparent actions of adenosine 5'-triphosphate (ATP) are mediated by adenosine produced by enzymatic hydrolysis of the nucleotide. Previously described actions of ATP in the CNS have been partly due to this phenomenon. In the present study analogues of ATP, which are not hydrolysed to adenosine, were used to seek responses to activating nucleotide (P2) receptors in the hippocampus. The analogues used were L-adenosine-5'-(beta,gamma-methylene)-triphosphonate and 2-methylthioadenosine-5'-(beta,gamma-difluoromethylene)-triphosphonat e. 2. Neither of the stable nucleotides had any effect on orthodromically evoked synaptic potentials in the CA1 region of rat hippocampal slices. Adenosine and ATP had inhibitory actions that could be prevented by the P1-receptor blocker 8-phenyltheophylline. 3. The stable nucleotides had no consistent effects on the firing rate of single neurones in stratum pyramidale of the CA1 region, although adenosine and ATP produced a xanthine-sensitive inhibition. 4. Adenosine selectively reduced the sensitivity of CA1 neurones to microiontophoretically applied carbachol whereas stable nucleotides did not. 5. It is concluded that there are neither P2x- nor P2y-receptors for adenine nucleotides on rat hippocampal CA1 pyramidal cells at the Schaffer collateral and commissural terminals in stratum radiatum.

Action Potentials↗