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Biomedical subjects

E A Brunner

Publications and source records attributed to E A Brunner.

At least 37 records · Page 2Linked to original sources
PubMed1981

Inhibition of GABA metabolism in rat brain slices by halothane.

Based on studies with rat cerebral cortex slices, it was previously hypothesized that halothane anesthesia may result from increased GABA (gamma-aminobutyric acid) content in the synapses. Since GABA is an inhibitory neurotransmitter, such increases may cause a reduction in synaptic activity. The increase in GABA content could arise from several possible causes which are examined in this study using rat cerebral cortex slices as a model. The effects of halothane on uptake, release, and catabolism of GABA were determined. Uptake was studied by the amounts of radioactive GABA accumulated by the slices, and release studied by that discharged into the medium from slices preloaded with radioactive GABA. Catabolism was assessed by preloading the slices with radioactive GABA and then followed by measuring the amount of radioactivity found in unmetabolized GABA or in pooled GABA metabolites. Since CO2 was established as a major metabolite, it was subsequently used alone to measure the inhibition of GABA catabolism in the presence of varying amounts of halothane. Halothane (3 per cent) did not affect the high-affinity uptake or the release of GABA but did inhibit the catabolism of GABA. Using 14CO2 production as an index of catabolism, the inhibition of GABA catabolism by halothane was dose-related (8.79 per cent inhibition/per cent halothane). Such results support the hypothesis that halothane anesthesia may result at least in part from an inhibition of GABA catabolism which, in turn, causes increased GABA level in the synapse with resultant synaptic inhibition.

Animals↗
PubMed1981

Effects of anesthetic agents on synaptosomal GABA disposal.

In brain slices, halothane was shown to inhibit the metabolic breakdown of GABA (gamma-aminobutyric acid), an inhibitory neurotransmitter. This inhibition leads to increased brain GABA content, presumably in the synaptic areas, and to the postulation that halothane anesthesia may arise from an enhanced synaptic inhibition due to this elevated GABA. The ability of many neurotropic agents to inhibit GABA breakdown was studied by assessing synaptosomal "GABA disposal". GABA disposal by intact synaptosomes, which simulate miniature synapses, measures the conversion of [1-14C]GABA to 14CO2 and includes the processes of uptake, release, and catabolism of GABA. The most potent inhibitor is chloroform, followed by halothane, enflurane, ether, and thiopental. Pentobarbital, ethanol, paraldehyde, and ketamine are weak inhibitors. Phenobarbital, morphine, and phenytoin are not inhibitory at pharmacologic concentrations. As a whole, anesthetic agents show particular inhibitory action on this metabolic process in this model system where the ID10 values (i.e., concentration of a drug necessary to produce 10 per cent inhibition of GABA disposal) correlate well with known pharmacologic potencies, ED50 values, or MACs. These observations support the possibility that anesthesia may be related to an inhibition of GABA disposal.

Anesthetics↗
PubMed1981

Inhibition of GABA metabolism in rat brain synaptosomes by midazolam (RO-21-3981).

Benzodiazepines are known to potentiate GABA (gamma aminobutyric acid) action in the brain. The effects of midazolam, a water-soluble benzodiazepine, on GABA disposal (14CO2 from [1-14C]GABA) and on the individual processes of GABA uptake, GABA release, and GABA-transaminase in the rat brain synaptosomal model system were studied. A 10 per cent inhibition of action was defined as ID10. Midazolam inhibited overall GABA disposal at ID10 = 13 micro M. The ID10 values for the three contributing process in the overall GABA disposal process are 580 micro M for GABA-transaminase activity, 96 micro M for GABA release, and 13 micro M for GABA uptake. The value for GABA release is probably not valid since it fell outside of the linear part of the regression line which was used for calculation. Therefore, GABA uptake inhibition appears to be responsible for the overall inhibition of GABA disposal. This value is consistent with the proposed hypothesis that anesthesia involves excess GABA in the synaptic area.

4-Aminobutyrate Transaminase↗
PubMed1980

Postdural puncture headache in patients with chronic pain.

The incidence of headache after dural puncture in patients being treated for chronic pain was studied prospectively. Dural punctures were performed in 142 patients and headache developed in 13 (9.2%). Four of 32 patients (12.5%) who underwent diagnostic differential spinal and nine of 110 patients (8.2%) given intrathecal steroid injection developed headache. There was a 10.7% incidence of headache when a 22-gauge needle was used as compared to 5% with a 25-gauge needle. This difference was not statistically significant. The incidence decreased with increasing age. The incidence of postdural puncture headache in chronic pain patients does not differ significantly from that previously reported for surgical patients. All patients who developed headache responded to treatment which consisted of intravenous and oral fluids, analgesics, bed rest, and, if necessary, epidural blood patch.

Adult↗
PubMed1975

Effects of anesthesia on intermediary metabolism.

Major inhalational anesthetics cause inhibition in the electron transport chain in the region of Complex I resulting in decreased oxygen utilization, inhibition of metabolism of NAD-linked substrates, but not of succinate, inhibition of mitochondrial calcium uptake, and depression of synaptic transmission because of postulated changes in ACh sensitivity or GABA inhibition. Many cellular metabolic effects in CNS and other tissues are secondary to the above. Many metabolic changes noted with anesthetics occur subsequent to activation of the sympathetic nervous system either directly by the anesthetic or by surgical stimulation in the presence of light anesthesia. Many important studies remain to be done.

Adenosine Triphosphate↗