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Biomedical subjects

B M Rigor

Publications and source records attributed to B M Rigor.

At least 37 records · Page 2Linked to original sources
PubMed1993

The neurotoxicity of sulfur-containing amino acids in energy-deprived rat hippocampal slices.

The rat hippocampal slice preparation and its electrophysiology were used to assess the toxicity of two sulfur-containing amino acids, L-cysteate (CA) and L-cysteine (CYS). Both compounds were innocuous under normal conditions but became toxic in energy-deprived (lack of oxygen or glucose) slices. CA and CYS toxicity was apparent as both reduced the number of slices that normally recover their neuronal function (evoked CA1 population spike) after a standardized period of hypoxia or glucose deprivation (GD). The competitive N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonovalerate blocked the toxicity of both CA and CYS in hypoxic slices, but it was effective only against CYS toxicity in glucose-deprived slices. The glycine antagonist 7-chlorokynurenate blocked CA and CYS toxicity in hypoxic slices but was unable to block their toxicity in glucose-deprived tissue. Perfusing slices with medium containing a high magnesium concentration blocked the toxicity of CA in both hypoxic and glucose-deprived slices, a treatment that was ineffective against CYS toxicity under either condition. Calcium depletion from the perfusion medium completely blocked the damaging effect of both amino acids in hypoxic slices, but it only partially blocked the toxicity of CA and did not block that of CYS in glucose-deprived slices. These results suggest that CA and CYS activate different NMDA receptor subsets and other glutamate receptor subtypes. Moreover, the results indicate a possible difference between the mechanism that lead to hypoxic neuronal damage and the one that lead to hypoglycemic neuronal damage.

Amino Acids, Sulfur↗
PubMed1992

The excitotoxicity of heterocyclic dicarboxylic acids in rat hippocampal slices: structure-activity relationships.

The structural resemblance of certain heterocyclic dicarboxylates to aspartate and glutamate led investigators to study their potency as agonists and antagonists of the N-methyl-D-aspartate (NMDA) receptor. The sensitivity of hypoxic rat hippocampal slices to NMDA ligands is several fold greater than that of normoxic slices. In the present study, the excitotoxic potency of heterocyclic dicarboxylates was assessed electrophysiologically by measuring their ability to enhance hypoxic and hypoglycemic neuronal damage in the rat hippocampal slice preparation. Four compounds were tested: quinolinate (QUIN), 4,5-imidazole-dicarboxylate (IZDA), 1,2,3-triazole-4,5-dicarboxylate (TZDA), and 2,3-pyrazinedicarboxylate (PZDA). QUIN was the most toxic drug in enhancing both hypoxic and hypoglycemic neuronal damage. IZDA and TZDA were slightly less toxic than QUIN, while PZDA was innocuous. The effect of the 3 active drugs was blocked by the NMDA competitive antagonist DL-2-amino-5-phosphonovalerate. The sequence -N-CH(COOH)-CH(COOH)- appears to be a prerequisite for a heterocyclic dicarboxylate to exert NMDA-type agonistic properties. A 5-membered ring heterocyclic compound which contains more than one nitrogen atom in its ring retains its NMDA-type toxicity while a 6-membered ring with more than one nitrogen atom (PZDA) does not.

Animals↗
PubMed1992

The mechanism of cerebral hypoxic-ischemic damage.

The four most prominent hypotheses on the cellular processes leading to hypoxic-ischemic neuronal damage or death are (1) the lactacidosis hypothesis, (2) the calcium overload hypothesis, (3) the excitotoxic hypothesis, and (4) the oxygen-free radical hypothesis. The authors comment on the evidence in favor of and against each in an attempt to select the one hypothesis that best explains the mechanism of cerebral hypoxic-ischemic damage while withstanding the scrutiny of scientific testing. A major part of this inquiry is derived from in vitro studies that are suited to mechanistic exploration. They conclude that the calcium overload hypothesis is the best qualified in this respect. It is important to note, however, that some of the other hypothetical mechanisms may play a secondary role in exacerbating neuronal damage by accelerating calcium influx and overload.

Animals↗
PubMed1992

Transient bradycardia associated with extradural blood patch after inadvertent dural puncture in parturients.

We have studied prospectively 10 ASA I or II postpartum patients after inadvertent dural puncture during labour. An extradural blood patch (autologous blood 15 ml) was performed within 18 h of delivery, with continuous EEG, upper facial EMG (Datex: Anesthesia and Brain Activity Monitor), pulse oximetry and heart rate measurement before, during and for 30 min after extradural injection. Non-invasive arterial pressure measurements (Dinamap) were recorded at 5-min intervals. After extradural blood patch, a statistically significant (Student's t test, P < 0.05) decrease in heart rate, from a mean baseline of 88.6 (SD 7.31) beat min-1 to 51.3 (7.6) beat min-1, occurred within 122.6 (16.9) s from the time of the EBP. Bradycardia was observed for a mean duration of 12.4 (1.1) s. Upper facial EMG, EEG, SpO2 and arterial pressure did not change.

Analgesia, Epidural↗
PubMed1991

Neurotoxicity of quinolinic acid and its derivatives in hypoxic rat hippocampal slices.

The excitotoxicity of quinolinic acid (2,3-pyridinedicarboxylic acid), a potent endogenous N-methyl-D-aspartate (NMDA)-type agonist, was characterized in the hypoxic hippocampal slice preparation. A series of other pyridinedicarboxylic acids was also tested in this preparation in order to obtain information about the structural requirements for the interaction between the NMDA receptor and its agonists. Of the 7 pyridinedicarboxylic acids tested, only quinolinic acid and its anhydride exerted their excitotoxicity by enhancing hypoxic neuronal damage in rat hippocampal slices at a relatively low concentration (100 microM). Much higher concentration (1 mM) of 3,4-pyridinedicarboxylic acid was required to exhibit any enhancement of hypoxic neuronal damage. The rest of the derivatives were innocuous. The effect of quinolinic acid was blocked by DL-2-amino-5-phosphonovaleric acid, by elevated magnesium levels in the incubation medium or by perfusion with a medium depleted of calcium. Aglycemic damage was also enhanced by quinolinic acid. It appears from the present study that two adjacent carboxylic groups on the pyridine ring, preferably at positions 2 and 3, are a prerequisite for an interaction between the NMDA receptor and its agonist. However, other factors may have great influence on that interaction as was evident from the total impotency of 6-methyl-quinolinic acid. The hypoxic hippocampal slice preparation and its neuronal function is an inexpensive model system, sensitized to the neurotoxins, and thus, allows the easy screening and evaluation of potential ligands of the glutamate receptor and its subtypes.

2-Amino-5-phosphonovalerate↗
PubMed1990

Treatment of cancer pain of the head and neck by continuous intravenous infusion of high-dose morphine: report of two cases.

Two pain-ridden patients in the terminal stage of a malignancy of the head and neck were treated with high-dose morphine which was administered as a continuous IV infusion along with a hyperalimentation solution using a pump. Good pain relief and a lessening of anxiety were achieved after failure to control pain in spite of the use of the analgesic ladder recommended by the WHO.

Female↗
PubMed1989

Cerebral ischemia revisited: new insights as revealed using in vitro brain slice preparations.

The elucidation of the pathophysiological mechanisms of cerebral ischemia/hypoxia dictates the use of experimental models which mimic this disabling brain condition. In vivo experimental models have been available for many decades and are responsible for the bulk of, though incomplete, knowledge we have about these mechanisms. Since study in isolation of each postulated mechanism is impossible in vivo, the need for an in vitro experimental model has intensified in recent years. Consequently, rat and guinea pig hippocampal slice preparations have emerged as the models of choice. This review attempts to highlight some of the results obtained using brain slices in the study of cerebral ischemia/hypoxia and compare them to those obtained in vivo. Both the biochemical and the physiological correlates of energy metabolism, ion homeostasis, neurotransmission and neuromodulation of this brain condition are reviewed. The agreements, and especially the disagreements, between the in vivo and in vitro findings are emphasized. Details are given of the possible roles of both lactic acid, Ca2+ and excitotoxins in the neuronal damage inflicted by cerebral ischemia/hypoxia. Recent attempts to protect brain slices against experimental cerebral ischemic/hypoxic damage are also reviewed here briefly.

Action Potentials↗
PubMed1989

Electrophysiology of energy metabolism and neuronal function in the hippocampal slice preparation.

The brain slice preparation offers a unique opportunity to study synaptic function in vitro. Employing electrophysiological methods to measure synaptic activity, we manipulated the extracellular environment of the rat hippocampal slice preparation: (1) by exposing it to different degrees of hypoxia, (2) by changing the levels of glucose, (3) lactate, and (4) H+, separately and in combination with each other. The lower the oxygen level during hypoxia and the longer its duration were, the lower was the recovery rate of synaptic function in the slice upon restoration of oxygenation. Reduction or complete depletion of glucose from the perfusion medium had similar effects, although synaptic function could recover after longer periods of glucose lack as compared with oxygen lack. Reduction in the levels of both oxygen and glucose had an additive effect on the recovery rate of synaptic function when compared with the effect of each of them alone. 'Hyperglycemic' concentration of glucose prolonged the hypoxic period slices could tolerate. Acidosis, induced either by lactic acid or HCl, had no adverse effect on hypoxic slices when the pH was held at or above 6.0 or when lactic acid concentration was below 20 mM. At 10 mM, lactic acid appeared to have a beneficial effect on hypoxic slices. Consequently, it was found that lactate can replace glucose as the sole aerobic energy substrate to support synaptic function in cerebral tissue in vitro.

Action Potentials↗
PubMed1989

Protection against cerebral hypoxia by local anesthetics: a study using brain slices.

The ability of the local anesthetics lidocaine, 2-chloroprocaine and cocaine to protect neuronal tissue against hypoxic damage was evaluated. Rat hippocampal slices were incubated with non-depressive doses of these agents 60 min prior to their exposure to 15 min hypoxia. The rate of recovery of synaptic function (evoked field potentials) following the hypoxic episode was used as an index of hypoxic damage. Slices treated with 0.1 mM of any of the three local anesthetics exhibited a significant increase in the recovery rate of synaptic function from hypoxia as compared to control, untreated slices. These results indicate that local anesthetics, by reducing neuronal sodium influx (and possibly its concomitant calcium influx) which occurs upon hypoxic depolarization, are able to prolong the hypoxic insult a cerebral tissue could tolerate.

Action Potentials↗
PubMed1988

Lactate-supported synaptic function in the rat hippocampal slice preparation.

The present study was undertaken to examine the possibility that cerebral energy metabolism can be fueled by lactate. As a sole energy substrate, lactate supported normal synaptic function in rat hippocampal slices for hours without any sign of deterioration. Slices that were synaptically silent as a result of glucose depletion could be reactivated with lactate to show normal synaptic function. When slices were exposed to the glycolytic inhibitor iodoacetic acid, lactate-supported synaptic function was unaffected, whereas that supported by glucose was completely abolished. This indicated that lactate was metabolized directly via pyruvate to enter the tricarboxylic acid cycle. Thus, under conditions that lead to lactate accumulation (cerebral ischemia) this "end product" may be a useful alternative as a substrate for energy metabolism.

Animals↗
PubMed1988

Lactic acidosis and recovery of neuronal function following cerebral hypoxia in vitro.

The rat hippocampal slice preparation was used to study the combined effects of hypoxia and lactic acidosis on neuronal function. Control slices were exposed to a standard hypoxic insult while being perfused with normal artificial cerebrospinal fluid (ACSF). Experimental slices were perfused with ACSF containing 1.0, 2.0, 10.0 or 20.0 mM lactic acid, 30 min before and during the same standard hypoxic insult. Following at 30-min recovery period the ability of these slices to respond to orthodromic stimulation by displaying a population spike (synaptic function) was tested. No significant decreases in the recovery rate of synaptic function were found between control and experimental groups, excluding the combination of 20 mM lactic acid and 10 min hypoxia, where such a decrease was found. The combination of 10 mM lactic acid and 12 min hypoxia brought about an increase in the recovery rate of synaptic function. Thus, the adverse effects attributed to lactic acid in vivo were not seen in the present in vitro study. Neuronal tissue appears to be able to handle excess lactic acid by yet, unknown mechanism (high intracellular buffer capacity?). The suggested in vivo damage due to lactic acidosis could originate in the cerebrovascular system. On the other hand, the possibility that lactic acidosis is harmless under hypoxic conditions should also be considered.

Acidosis, Lactic↗
PubMed1988

Objective assessment of opioid action by facial muscle surface electromyography (SEMG).

1. Activity of the mimetic muscles of the upper face were recorded from awake and anesthetized patients by surface electromyography (SEMG). 2. High amplitude SEMG accompanied ketamine anesthesia and/or the presentation of pain-provoking stimuli. 3. During periods of elevated facial muscle activity, fentanyl or butorphanol decreased SEMG amplitude. 4. The opioid-induced SEMG depression was not consistently associated with either lowered vigilance or analgesia but did provide an objective measure of drug effect.

Adult↗
PubMed1987

The mechanism of neuronal resistance and adaptation to hypoxia.

In this work we provide a theoretical explanation for the observations that: (i) young animals are more resistant to hypoxia than adult ones and (ii) repeated exposure to a hypoxic insult increases the tolerance of young animals and isolated brain tissue to that insult. Considered here is the role of taurine, a putative Ca2+ transport modulator, in attenuating Ca2+ influx and overload in brain tissue upon hypoxia. It is proposed that the higher resistance of young animals to hypoxia stems from their higher brain content of taurine as compared with adults. The increased resistance to lack of oxygen upon re-exposure to hypoxia may occur as a result of protein and coenzyme A (CoA) breakdown which leads to the accumulation of products like cystine, cysteine, cysteamine and other sulfur-containing compounds. Upon reoxygenation, these compounds are oxidized to form taurine, which in turn attenuates neuronal Ca2+ accumulation. The sulfur-containing compounds are considered to be natural scavengers of oxygen-derived free radicals which are formed upon reoxygenation and have been implicated as a major component in the process leading to ischemic/hypoxic brain damage. Repeated hypoxic insults bring about the formation of higher levels of taurine and hence the observed adaptation to oxygen lack. The hypothesis presented here is supported by experimental observations in our laboratory and those of others.

Adaptation, Physiological↗
PubMed1987

Increased glucose improves recovery of neuronal function after cerebral hypoxia in vitro.

The rat hippocampal slice preparation was used to evaluate the effect of increasing glucose levels in the perfusion medium on the recovery of synaptic function after a standardized hypoxic insult. Slices exposed to low glucose (5 mM) did not recover from a standard hypoxic insult (10 min of 95% N2/5% CO2 atmosphere). Following the same insult, 39% of the control (10 mM glucose) slices recovered their synaptic function, while 93% of the slices provided with high glucose level (20 mM) exhibited recovery of synaptic function. Thus, a dose-dependent effect of glucose on recovery of neuronal function following an intermediate period (10 min) of oxygen deprivation was found. The high-glucose-treated slices could tolerate a severe hypoxic insult of 15 min or even 20 min from which 94% and 81% of them recovered, respectively. Only 21% of the control (10 mM glucose) slices recovered their synaptic activity following 15 min of hypoxia, and none survived 20 min of that insult. The adverse effects of hyperglycemia reported in vivo were not seen in our study. This may be due to the sustained perfusion of the brain slice preparation, which could limit accumulation of lactic acid during hypoxia. However, treatment of slices with lactic acid prior to and during the hypoxic insult did not worsen the outcome. Alternatively, glucose may protect against the damaging effects of oxygen free radicals formed during reoxygenation. Nevertheless, the antihypoxic effect of glucose appears to be a metabolic one, since L-glucose (the non-metabolic analog of D-glucose) was innocuous in this respect.

Animals↗
PubMed1987

Glutamine protects neuronal function against cerebral hypoxia: a study using the in vitro hippocampal slice preparation.

Pretreatment of hippocampal slices with glutamine doubled the recovery rate of the synaptic function (electrically evoked population spike) from a standardized hypoxic insult in CA1 pyramidal neurons. This protective effect of glutamine was dose-dependent and biphasic; recovery of synaptic function was observed in 44% of the control slices and in 55%, 90%, 92% and 0% of slices pretreated with 0.1, 1.0, 5.0 and 10.0 mM glutamine, respectively. The synaptic function did not recover after hypoxia in slices pretreated with glutamic acid (1.0 mM).

Animals↗
PubMed1987

Taurine improves the recovery of neuronal function following cerebral hypoxia: an in vitro study.

Rat hippocampal slices were used in the present study to assess the effect of a pretreatment with the amino acid taurine on their ability to recover synaptic function following a standardized hypoxic insult. After 10 min hypoxia, 47% of all control (untreated) slices exhibited recovery of synaptic function (orthodromically evoked CA1 population spike). Of slices pretreated with 0.5, 1.0 or 2.0 mM taurine, 63, 88 and 97% recovered from the same hypoxic insult. This dose-dependent protective effect was biphasic, as 5.0 mM taurine produced no protection. When hypoxia was extended to 15 min, only 20% of the untreated slices recovered, while 88% of slices treated with 1.0 mM taurine recovered their population spike. The same pretreatment attenuated the fall in the population spike amplitude upon Ca2+ depletion. We hypothesize that taurine plays an important role in an endogenous antihypoxic mechanism through the attenuation of Ca2+ movement across the neuronal membrane.

Animals↗