Biomedical subjects

D A Richards

Publications and source records attributed to D A Richards.

At least 37 records · Page 2Linked to original sources

PubMed1996

Comparative effects of the GABA uptake inhibitors, tiagabine and NNC-711, on extracellular GABA levels in the rat ventrolateral thalamus.

The primary mechanism by which the action of synaptically released GABA is thought to be terminated is by re-uptake into neurones and glial cells, and the pharmacological inhibition of this uptake may be beneficial in conditions where decreased GABAergic transmission has been implicated, such as epilepsy. We have compared the effects of two of these uptake inhibitors, tiagabine and NNC-711, on extracellular GABA levels in the thalamus of the rat, after both systemic and local administration. Both compounds produced dose-dependent increases in GABA concentration irrespective of the route of administration, but the concentrations required to produce increased extracellular GABA levels were considerably higher than those known to be effective for anticonvulsant purposes. These data suggest that, initially at least, alternative GABA transporters, not susceptible to inhibition by the compounds used, may still be able to remove synaptically released GABA from the extracellular space.

Analysis of Variance↗

PubMed1996

Infrared thermometry in the diagnosis and treatment of heat exhaustion.

Infrared (IR) thermometers (FirstTemp 2000A, Intelligent Medical Systems, California) were used to monitor tympanic temperature (Tty) in 12 collapsed fun-runners suspected of suffering exertion-induced heat exhaustion (EIHE). Rectal temperature (Tre) was monitored via digital clinical thermometers. Conditions during the fun-run and in the field treatment centre were cool (air temperature 16-18 degrees C, relative humidity 60-65%). On admission, Tty was (mean +/- SEM) 1.2 +/- 0.3 degrees C lower than Tre. For admission plus subsequent monitoring data pooled, although Tty correlated significantly with Tre (r = 0.86, p < 0.001), mean Tty (37.4 +/- 0.2 degrees C) was significantly lower (p < 0.01) than mean Tre (38.4 +/- 0.4 degrees C). Cotton wool ear pads, applied to 10 of the runners on admission to minimise environmental effects on Tty, did not significantly improve the IR monitoring. A Tty > or = 37.1 degrees C predicted a Tre > or = 38 degrees C (an established diagnostic criterion for EIHE) with a sensitivity of 0.93 and a specificity of 0.63. These data indicate that IR tympanic thermometry, when utilised in cool environments, can result in misdiagnosis of heat exhaustion. Although IR thermometry shows some promise as a rapid, non-invasive means of monitoring core temperature, it should not be used in the diagnosis and treatment of heat exhaustion unless further research validates the method.

Adult↗

PubMed1995

Does the induction of ventricular flutter or fibrillation at electrophysiologic testing after myocardial infarction have any prognostic significance?

This study examines the significance of inducing sustained ventricular fibrillation (VF) or ventricular flutter by programmed stimulation after infarction. Programmed ventricular stimulation was performed for prognostic reasons from the right ventricular apex at twice diastolic threshold using a protocol containing 4 extrastimuli. Of 502 patients tested 11 +/- 4 days after acute infarction, VF was induced in 164 (33%), ventricular flutter in 134 (27%), ventricular tachycardia (VT) in 44 (9%), and no arrhythmia in 160 (32%). All groups were similar in age, sex distribution, and sites of index infarction. Those with inducible VT had a higher incidence of multiple infarctions and a lower mean left ventricular ejection fraction at the time of testing. Without antiarrhythmic drug therapy, 8 patients (18%) with inducible VT experienced spontaneous VT or died instantaneously during the first year of follow-up. By contrast, only 1 (0.6%) patient with inducible VF, 1 (0.7%) with ventricular flutter, and 1 (0.6%) without any inducible arrhythmias experienced similar events in the same period (p < 0.001). By relating the cycle length of the induced monomorphic arrhythmia to later spontaneous electrical events, induced arrhythmias with cycle length as low as 230 ms still identified patients at high risk for spontaneous arrhythmias. Only the induction of sustained monomorphic VT with a cycle length > 230 ms indicates patients with ventricular electrical instability after infarction. The induction of VF or ventricular flutter is a negative test result with no adverse long-term prognostic significance.

Arrhythmias, Cardiac↗

PubMed1995

Extracellular GABA in the ventrolateral thalamus of rats exhibiting spontaneous absence epilepsy: a microdialysis study.

There is compelling evidence that excessive GABA-mediated inhibition may underlie the abnormal electrical activity, initiated in the thalamus, associated with epileptic absence seizures. In particular, the GABAB receptor subtype seems to play a critical role, because its antagonists are potent inhibitors of absence seizures, whereas its agonists exacerbate seizure activity. Using a validated rat model of absence epilepsy, we have previously found no evidence of abnormal GABAB receptor density or affinity in thalamic tissue. In the present study, we have used in vivo microdialysis to monitor changes in levels of extracellular GABA and other amino acids in this brain region. We have shown that basal extracellular levels of GABA and, to a lesser extent, taurine are increased when compared with values in nonepileptic controls. However, modifying GABAergic transmission with the GABAB agonist (-)-baclofen (2 mg/kg i.p.), the GABAB antagonist CGP-35348 (200 mg/kg i.p.), or the GABA uptake inhibitor tiagabine (100 microM) did not produce any further alteration in extracellular GABA levels, despite the ability of these compounds to increase (baclofen and tiagabine) or decrease (CGP-35348) seizure activity. These findings suggest that the increased basal GABA levels observed in this animal model are not simply a consequence of seizure activity but may contribute to the initiation of absence seizures.

Animals↗

PubMed1995

Rapid intravenous infusion of d-1 sotalol: time to onset of effects on ventricular refractoriness, and safety.

d-1 sotalol is one of the most effective antiarrhythmic agents currently available for ventricular tachyarrhythmias, but the recommended infusion rate of 10-20 min is too slow for rapid pharmacological termination of sustained ventricular tachycardia (VT) or for use during cardiac arrest. The safety of the drug and time lag from its rapid administration to onset of significant effects on ventricular refractoriness is unknown. One hundred and nine patients with a history of spontaneous and inducible sustained ventricular tachyarrhythmias were studied. d-1 sotalol (1.5 mg.kg-1) was infused over 5 min in the first 57 patients (mean age 61 +/- 13 years, mean ejection fraction 37 +/- 15%, range 15-70%). d-1 sotalol was then given over 1 min in the next 52 patients (mean age 61 +/- 12 years, mean ejection fraction 35 +/- 11%, range 18-58%). The time course of change in right ventricular effective refractory period (RVERP) was measured in 15 consecutive patients following the 5 min infusion and in all 52 patients following the bolus injection. Following the 5 min infusion, RVERP increased rapidly from a baseline of 231 +/- 17 ms, reaching a plateau of 268 +/- 23 ms at 10 min. Following the 1 min injection, RVERP increased virtually immediately from a baseline of 237 +/- 25 ms to reach a plateau of 271 +/- 31 ms at 5 min. Two patients (one in each group) developed symptomatic hypotension; both responded to volume replacement.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Deaths in a heat wave.

Faunt et al., have reminded us of the lethal potential of heat-related illness, and emphasised the need for thoughtful prophylaxis to reduce the morbidity and mortality of this largely preventable disease. A high index of suspicion of the presence of heat-related illness in susceptible individuals is essential. Cooling is best achieved by judicious use of fluid replacement along with other resuscitation as necessary.

Heat Exhaustion↗

PubMed1995

Simultaneous mapping of the tricuspid and mitral valve annuli at electrophysiological study.

BACKGROUND: Mapping of the right free wall in patients with accessory pathways is difficult compared with that of the left free wall where the coronary sinus permits stable and accurate location of the electrodes used for endocardial mapping. Furthermore, the sequential roving catheter method is less satisfactory than multiple simultaneous electrode recordings spanning the circumference of the valve annulus. A new method for mapping the tricuspid annulus is described. METHODS: Mapping was performed in nine patients with a suspected right free wall accessory pathway or an atriofascicular connection. The tricuspid annulus was mapped using a specially shaped 1 cm interelectrode 10 pole catheter positioned in the right atrium immediately above the annulus. The coronary sinus was mapped with a 5 mm interelectrode 10 pole catheter and a 2 mm interelectrode 10 pole catheter recorded His bundle activity. Catheter positions were confirmed by multiplane fluoroscopy. Electrograms were digitised and recorded simultaneously using a custom computerised mapping system. The position of the multielectrode catheter around the tricuspid annulus relative to that of the coronary arteries was examined by coronary angiography in three patients. RESULTS: Seven right free wall and two posterior septal accessory pathways, and three atriofascicular connections were detected. Ventricular activation adjacent to both valve annuli was mapped in five patients with pre-excitation. The locations of eight of the nine accessory pathways and the three atriofascicular connections were confirmed at operative mapping. One right free wall accessory pathway in a patient with Ebstein's anomaly was not detected at operative mapping. No additional accessory pathways were found at operative mapping or routine 6 month postoperative electrophysiological study, or during a mean (SD) clinical follow up of 22 (7) months. The tricuspid annulus catheter was located during coronary angiography at a mean (SD) of about 2.5 (0.7) cm above and parallel to the right coronary artery in the right atrioventricular groove. CONCLUSIONS: This new catheter technique permits rapid detailed mapping of atrial and ventricular activation around the tricuspid annulus with a resolution of at least < or = % 1 cm, depending on the number and spacing of electrodes in each catheter. The technique was accurate as judged by mapping at surgery. This method is simple and safe compared with that of others for mapping the right free wall via the right coronary artery. It should facilitate detection and ablation of right free wall accessory pathways and atriofascicular connections.

Adolescent↗

PubMed1995

Effects of 5-fluorouracil treatment on rat liver microsomal enzymes.

1. The effects of the administration of the anticancer drug 5-fluorouracil on P450-mediated metabolizing capacity, and the activity of several related enzymes were examined by comparing two different dosage regimes, i.e. a single ip dose of 5-fluorouracil (120 mg/kg) at 1, 4 and 7 days prior to killing, and a repeated dose regimen of 5-fluorouracil (24 mg/kg/day for 5 consecutive days) with animals being killed at 1, 4 and 7 days after the last 5-fluorouracil dose. 2. Rat liver microsomes were assayed for total P450 content, reduced nicotinamide adenine dinucleotide phosphate-P450-reductase, aminopyrine demethylase, cyclophosphamide 4-hydroxylase, aniline hydroxylase, androstenedione 6 beta- and 16 alpha-hydroxylase and delta 4-3-oxo-steroid 5 alpha-oxidoreductase activity. 3. The animals that received 5-fluorouracil as a single, high dose did not show any alterations in any of the measured parameters at any of the times at which they were killed. 4. The animals that received chronic low doses of 5-fluorouracil, however, showed a statistically significant decrease in androstenedione 6 beta- and 16 alpha-hydroxylase and cyclophosphamide 4-hydroxylase activity and a statistically significant increase in delta 4-3-oxo-steroid 5 alpha-oxidoreductase activity 4 and 7 days after completion of dosing. 5. Immunoquantified P4502C11 and 3A content was also decreased at these time points. These alterations occurred concurrently with depleted plasma testosterone levels in the groups that received repeated low doses of 5-fluorouracil.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1995

Extracellular neurotransmitter changes in cerebral ischaemia.

The discovery that blockade of N-methyl-D-aspartate (NMDA) receptors protects brain tissue against ischaemic damage has triggered enormous interest; and with the advance of intracerebral microdialysis, hundreds of studies have investigated changes in the extracellular levels of glutamate and other neurotransmitters during and after cerebral ischaemia. This work has made it apparent that the current concept of ischaemia-induced excitotoxicity, centred on excessive efflux of glutamate from nerve terminals, fails to correspond with reality since it conflicts with a number of key findings: (a) Excessive effluxes during ischaemia are not specific to excitatory amino acids--inhibitory transmitters are released to a similar extent; (b) neuronal death can occur several hours after a short ischaemic episode, whereas glutamate and aspartate accumulation in the neuronal microenvironment is cleared within minutes of reperfusion; (c) the penumbra is most receptive to cerebroprotection with glutamate receptor antagonists, but extracellular glutamate levels may not reach critical levels in this region; and (d) postischaemic treatment with glutamate receptor antagonists were neuroprotective in a number of studies. It has also become evident that most of the glutamate released in ischaemia is of metabolic origin, which questions the validity of therapeutic strategies aimed at preventing or reducing excessive release of neurotransmitter glutamate in ischaemia. However, the possibility that glutamate changes at the synaptic level may be small but pathologically important cannot be totally refuted. Apart from increased extracellular glutamate, the exceptional complexity of glutamate-operated ion channels can give rise to many potentially damaging mechanisms. Of particular interest are the possibilities of recurrent spreading depression in focal ischaemia, widespread and persistent strengthening of glutamatergic transmission, and abnormal modulation of the NMDA receptor-ionophore complex. There is also considerable evidence that, in certain brain regions, monoamines or their metabolic by-products may become neurotoxic either directly or from interplay with glutamatergic systems. All these processes deserve further examination to identify the most damaging and to indicate possible methods of intervention.

Amino Acids↗

PubMed1994

Heat exhaustion in The Sun-Herald City to Surf fun run.

OBJECTIVE: To investigate the relationship between motivational factors and physical and biological causes of heat exhaustion in fun run entrants. DESIGN AND SETTING: Case-control study, The Sun-Herald City to Surf fun runs in Sydney in 1991 and 1992. PARTICIPANTS: There were 63,732 race entrants who completed the run and received a finishing time; 79 runners with heat exhaustion and 310 age, sex and performance matched controls were enrolled in the study. MAIN OUTCOME MEASURE: A diagnosis of heat exhaustion was made if a runner collapsed and, when first receiving medical care, had a rectal temperature of 38 degrees C or higher. RESULTS: Two readily identifiable groups of runners were at high risk of heat exhaustion--accomplished non-élite (preferred) runners and runners of good ability (Group A). The attack rate was highest among accomplished non-élite runners, but a combination of a relatively high rate and the large number of entrants in Group A runners accounted for most cases. Four major risk factors for heat exhaustion were identified: motivation to exceed previous performance targets; failure to drink fluids during the run; failure of trained runners to acclimatise for the race by training in the warmer parts of the day; and previous history of heat exhaustion. CONCLUSION: Information from this investigation will enable more effective targeting of educational prevention programs in The Sun-Herald City to Surf fun run and provide baseline data for monitoring the effectiveness of these programs to modify high risk behaviour by participants.

Adolescent↗

PubMed1994

Double-blind trial of lignocaine versus sotalol for acute termination of spontaneous sustained ventricular tachycardia.

The efficacy of antiarrhythmic drugs for terminating sustained ventricular tachycardia (VT) has been disappointing. Lignocaine is the traditional drug but it is not very effective. Sotalol, one of the most effective drugs in suppressing spontaneous or induced VT, should theoretically be useful in this setting. We have compared lignocaine with sotalol for the acute termination of spontaneous sustained VT not causing cardiac arrest in 33 patients (26 males, 7 females, aged 21-90) whose underlying heart disease was old myocardial infarction (28), acute myocardial infarction (2), dilated cardiomyopathy (1), or idiopathic cardiomyopathy (2). Left-ventricular ejection fraction was 35% (range 18-76%). Patients were randomly allocated in a double-blind fashion to lignocaine 100 mg (n = 17) or sotalol 100 mg (n = 16) given intravenously over 5 min. Those with persistent VT 15 min after onset of administration of the first drug were crossed over to the other drug. Sotalol was significantly more effective than lignocaine whether analysed on an intention-to-treat basis (69% vs 18%; 95% confidence interval for absolute difference of 51% 22-80%, p = 0.003) or by analysis limited to the 31 patients with subsequent electrophysiologically proven VT (69% vs 20%). 1 patient in each group required cardioversion after the first drug. Tachycardia persisted in 14 patients in the lignocaine group and 4 in the sotalol group after 15 min. Tachycardia ceased in 7 (50%) patients who crossed over to sotalol, and in 1 patient who crossed over to lignocaine. There was 1 death in each group after the first drug and 1 death after both drugs. We conclude that sotalol was superior to lignocaine for the acute termination of sustained VT. The incidence of adverse effects was similar for the two drugs.

Adult↗

PubMed1994

Can the electrophysiologic study predict treatment outcome in patients with sustained ventricular tachyarrhythmias unrelated to coronary artery disease?

UNLABELLED: Sustained ventricular tachyarrhythmias unrelated to coronary artery disease are uncommon. Currently there are no clear guidelines to aid selection of the most appropriate treatment strategy. Therefore, factors potentially predictive of arrhythmia recurrence and death and the ability of the electrophysiologic study to predict treatment outcome in patients with spontaneous sustained ventricular tachyarrhythmias unrelated to coronary artery disease were examined in 41 medically treated patients followed for a median of 25 (range 1-76) months. Examined factors were: syncope associated with the spontaneous arrhythmia, the morphology and cycle length of the presenting arrhythmia, underlying ventricular function, cardiac pathology, and the results of drug assessment at electrophysiologic study. Random variability in the ease of arrhythmia induction at electrophysiologic study was measured for the group as a whole and was allowed for in prediction of an effective drug response. The 95% confidence intervals for variability in the ease of repeat arrhythmia induction at the same study were < or = 1 extrastimulus and for variability in the ease of repeat arrhythmia inductions at different studies were < or = 2 extrastimuli. Poisson regression models were used for data analysis. Arrhythmia recurrence was most likely in: (1) patients on treatment not predicted to be anti-arrhythmic at electrophysiologic study; (2) patients whose treatment was not assessable at electrophysiologic study because the arrhythmia was not reliably inducible; (3) patients with impaired ventricular function; and (4) re-entered patients whose arrhythmia had recurred on previously allocated therapy. The risk of arrhythmia recurrence decreased with time from hospital assessment. All five deaths occurred in patients with impaired ventricular function. CONCLUSIONS: drug efficacy should be tested at electrophysiologic study in patients with reproducibly inducible clinical arrhythmias. Treatment not proven to be anti-arrhythmic at electrophysiologic study is usually ineffective. Patients with ventricular dysfunction are at highest risk of death from arrhythmia recurrence and should be considered for an implantable defibrillator, arrhythmia surgery, or heart transplantation if drug treatment is not predicted to be effective or is not assessable at electrophysiologic study.

Adolescent↗

PubMed1994

N-methyl-D-aspartate receptors modulate extracellular 5-hydroxytryptamine concentration in rat hippocampus and striatum in vivo.

The effects of infusing N-methyl-D-aspartate (NMDA) and the specific NMDA receptor antagonist D-2-amino-5-phosphonopropionic acid (D-AP5) into rat hippocampus and striatum on extracellular 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxy-indoleacetic acid (5-HIAA) were studied using intracerebral microdialysis. In striatum, NMDA (1-100 microM) caused a concentration-dependent increase in 5-HT. D-AP5 (10 microM) infusion caused increased extracellular 5-HT. When the two drugs were co-infused, no effect on extracellular 5-HT was seen. D-AP5 alone was found to cause a delayed but sustained increase in dialysate 5-HIAA. In hippocampus, NMDA infusion caused a dose-dependent decrease in extracellular 5-HT while D-AP5 produced a transitory increase in 5-HT level. NMDA caused a decrease in dialysate 5-HIAA. In striatum, the effect of 10 microM NMDA infusion was abolished by co-infusion with tetrodotoxin (TTX; 1 microM). In hippocampus, 1 microM TTX caused a slight but non-significant augmentation of the effect of 10 microM NMDA alone. These data indicate that NMDA receptors mediate control over 5-HT release and metabolism in different brain regions and may in part explain the behavioural effects of non-competitive NMDA receptor antagonists.

2-Amino-5-phosphonovalerate↗

PubMed1994

Posterior ("atypical") atrioventricular junctional reentrant tachycardia.

The aim of this study was to characterize a relatively rare type of atrioventricular (AV) junctional reentrant tachycardia (AVJRT). Posterior AVJRT is a type of AV nodal tachycardia in which the site of earliest atrial activation is posterior to the AV node near the coronary sinus orifice. The mechanism of this tachycardia is not well understood. The characteristics of posterior AVJRT (n = 15) were compared with those of anterior ("common") AVJRT (n = 146) and supraventricular tachycardia using single posterior septal accessory pathways (n = 13). During posterior AVJRT, the AH interval was longer than the retrograde conduction time (His to earliest atrial activity) in 11 cases (73%), indicating that these tachycardias were not fast-slow types of AVJRT. The mean ventriculoatrial (VA) interval in posterior AVJRT (93 +/- 41 ms) was longer than in anterior AVJRT (11 +/- 20 ms; p < 0.005), but was similar to that in tachycardias using accessory pathways (106 +/- 16 ms; p = NS). The site of earliest atrial activation during posterior AVJRT was similar to that in tachycardias using accessory pathways. In all cases of accessory pathway-mediated tachycardia, atrial activation could be advanced by ventricular extrastimuli delivered coincident with the His deflection, but atrial activation was not advanced in any case of posterior AVJRT unless the extrastimulus was delivered > 80 ms before the His deflection. Anterograde conduction was similar in the posterior and anterior AVJRT groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Post-traumatic stress disorder: evaluation of a behavioral treatment program.

The relative values of imaginal and real-life exposure exercises were tested in this study by randomizing 14 patients who met DSM-III-R criteria for PTSD at least 6 months after the initiating trauma to one of two groups. Group 1 (n = 7) had four, weekly, hour-long sessions of imaginal exposure followed by four, weekly, hour-long sessions of live exposure. Group 2 (n = 7) had the reverse order of four live exposure sessions followed by four imaginal exposure sessions. both groups improved significantly on both PTSD-specific measures and measures of general health post-treatment, and significantly further on 7 out of 12 measures at follow up 12 months post-treatment. Clinical improvement was in the older of 65-80% reduction in target symptoms. On one measure only (problem 2--phobic avoidance), live exposure yielded more improvement than imaginal exposure whether given first or second. The importance of both live and imaginal exposure to all relevant cues, behavioral and cognitive, is discussed, together with the value of self-exposure homework for patients with PTSD.

Adolescent↗

PubMed1994

Simultaneous 60-electrode mapping of ventricular tachycardia using percutaneous catheters.

OBJECTIVES: We developed a new approach for mapping ventricular tachycardia at electrophysiologic study using simultaneous recordings from up to 60 catheter electrodes. BACKGROUND: Good results for surgical or catheter ablation of ventricular tachycardia are limited by the ability to detect and completely map all of the underlying arrhythmogenic areas. Currently, catheter mapping of all configurations of ventricular tachycardia is impossible or unsatisfactory in at least 60% of patients because of poorly tolerated rapid rates, nonsustained ventricular tachycardia or multiple configurations. METHODS: Twenty-four patients with recurrent ventricular tachycardia refractory to antiarrhythmic drugs were studied using up to six percutaneous decapolar catheters introduced into the ventricles. Left ventricular maps of ventricular tachycardia were achieved by two to three transseptal catheters, two to three transaortic catheters, a coronary sinus catheter and right ventricular catheters. Simultaneous endocardial maps of either right or left ventricles were possible with a resolution of approximately 1 to 2 cm. Up to 60 electrograms were digitized and recorded simultaneously using a custom-computerized mapping system. RESULTS: Successful maps of 73 ventricular tachycardia configurations were obtained in 22 patients. The mapping procedure failed in two patients because of inability to catheterize the left ventricle in one and inability to induce monomorphic ventricular tachycardia in the other. The mean (+/- SD) ventricular tachycardia cycle length was 285 +/- 53 ms (range 215 to 470). A total of 39 separate arrhythmogenic areas (median 1, interquartile [25% to 75%] range 1 to 3/patient) were detected, of which 21 (54%) were in the left ventricular free wall, 17 (44%) were in the ventricular septum, and 1 (2%) was in the right ventricular outflow tract. Ten patients (45%) had at least two arrhythmogenic areas. Thirteen patients subsequently underwent operation. All but one of the arrhythmogenic areas found at surgical mapping had been identified at preoperative catheter mapping. Complications of the preoperative mapping procedure occurred in four patients, with complete resolution in three and minor long-term sequelae in the other. CONCLUSIONS: This technique permits detailed catheter mapping of all types of monomorphic ventricular tachycardias, including those leading to hemodynamic collapse, and should enable better choice and direction of surgical or catheter ablation.

Adult↗

PubMed1994

Extracellular N-acetylaspartate in the rat brain: in vivo determination of basal levels and changes evoked by high K+.

The purpose of this study was to determine the extracellular concentrations of N-acetylaspartate (NAA) in the rat cerebral cortex, striatum, and hippocampus of halothane-anaesthetised rats by intracerebral microdialysis, and to examine the effects of high K(+)-induced local depolarisation, which provokes synchronous neurotransmitter release, cell swelling, and acid-base changes. Basal levels of NAA in the extracellular fluid (ECF) were determined by the zero net flux method. Tissue levels of NAA in the cortex, striatum, and hippocampus were 8.4, 5.7, and 7.2 mmol/kg, respectively. The corresponding extracellular concentrations of NAA were much lower (35.1, 83.7, and 23.0 microM). High tissue/ECF concentration ratios may suggest little release or leakage of NAA under basal conditions, and potent reuptake mechanisms for NAA in the cellular membrane of CNS cells. There was no change in ECF NAA during K(+)-induced local depolarising stimuli produced in the striatum, but NAA levels consistently increased after the K+ stimuli, irrespective of whether or not Ca2+ was present in the perfusion medium. These data confirm that NAA is not a neurotransmitter and suggest strongly that NAA is not directly involved in the release and reuptake or metabolism of neuroactive compounds. The increase of NAA in the ECF immediately after K+ stimulation may reflect an involvement in brain osmoregulation and/or acid-base homeostasis.

Animals↗

PubMed1994

Time course of changes in extracellular lactate evoked by transient K(+)-induced depolarisation in the rat striatum.

The purpose of this study was to establish whether excessive lactate production associated with local application of K+ is reflected at the extracellular level during or after the K+ challenge. Changes in extracellular lactate were continuously monitored by microdialysis coupled to on-line fluorimetric analysis. K(+)-induced changes in dialysate lactate were closely related to those of the direct current potential. High K+ evoked a large and sustained negative shift of direct current potential onto which were superimposed a variable number of transient peaks of further depolarisation. The initial negative shift in direct current potential was associated with a decrease in dialysate lactate, but after each transient depolarisation, the positive shift in direct current potential indicating cell repolarisation was associated with a marked increase in extracellular lactate. When repetitive transient depolarisations occurred during a stimulus, only a small increase after each depolarisation was observed. However, recordings consistently revealed a marked and rapid increase in extracellular lactate after the K+ stimulus. These data indicate that extracellular lactate mostly increased during periods of repolarisation. This suggests strongly that lactic acid transport out of brain cells may be impaired when their transmembrane ionic gradients are disrupted.

Animals↗