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J Krieglstein

Publications and source records attributed to J Krieglstein.

At least 181 records · Page 10Linked to original sources
PubMed1980

Studies on the linkage of energy metabolism and neuronal activity in the isolated perfused rat brain.

An isolated rat brain preparation was perfused using glucose-free (= aglycemic) media. The high-energy phosphates, substrates of the glycolytic pathway, free amino acids, acetylcholine as well as the intracellular distribution of hexokinase activity were determined in brain tissues. The EEG was evaluated visually. The levels of glycolytic substrates, glutamate, and glutamine in cortical tissue decreased after aglycemic perfusion whereas the asparte level increased and the GABA level remained unchanged. The high-energy phosphate content seemed to be unaffected for about 15 min of aglycemic perfusion and fell significantly after 20 min. The EEG of the isolated brain changed rapidly after starting aglycemic perfusion and became isoelectric after 12--15 min. Hyperglycemic perfusion (35 mmol glucose per liter perfusion medium) did not alter the energy metabolism of the isolated brain. The breakdown of cerebral energy metabolism and of EEG activity was postponed when thiopental was added to the perfusion medium. The soluble hexokinase activity measured in cortical tissue was reduced after aglycemic perfusion and was enhanced after thiopental. Hyperglycemic perfusion did not influence the intracellular hexokinase distribution. The acetylcholine level in the striatum of the isolated rat brain was significantly decreased by aglycemia and was increased in hypothalamus by thiopental. It was suggested that hexokinase bound to the mitochondrial membrane may play an important role in the relationship of energy metabolism and neuronal activity.

Acetylcholine↗
PubMed1980

Key enzymes of glycolysis in brain as influenced by thiopental.

It has been demonstrated in previous work that hexokinase is solubilized from the mitochondrial membrane in anesthesia. In the present investigation this effect was strongly correlated with the surgical stage of anesthesia by the application of thiopental to rats (80 mg/kg), mice (100 mg/kg) and guinea pigs (32 mg/kg). The solubilization of hexokinase was demonstrable, too, in different areas of rat brains under thiopental treatment (80 mg/kg). In order to elevate the cerebral concentration of glucose 6-phosphate, which is the most potent substrate for the solubilization of bound hexokinase, male Sprague-Dawley rats were pretreated with the antimetabolite 6-aminonicotinamide (6-AN). After i.p. injection of 6-AN (35 mg/kg) we measured an increased activity of soluble brain hexokinase in the same order of magnitude as it was determined in anesthesia. Thiopental application did not show a further significant increase. A solubilization of hexokinase activity by 6-AN was not measurable in vitro. Furthermore, we examined the other key enzymes in the glycolytic pathway. We found a competitive inhibition of phosphofrucktokinase activity by thiopental, but no inhibition of hexokinase and pyruvate-kinase activity.

Anesthesia↗
PubMed1979

Effects of chlorpromazine and some of its metabolites on the EEG and on dopamine metabolism of the isolated perfused rat brain.

The study concerned the effects of chlorpromazine (CPZ), monodesmethyl-chlorpromazine (NOR1-CPZ), didesmethyl-chlorpromazine (NOR2-CPZ), and chlorpromazine-N-oxide (CPZ-NO) on the EEG and on dopamine metabolism of the isolated perfused rat brain. Isolated brains were perfused with 100 ml of a perfusion medium containing 30% bovine red cells (v/v), 2 g bovine serum albumin, 14 mM glucose as well as one of the agents in a concentration of 10 micrometers. The main dopamine metabolite homovanillic acid (HVA) was measured fluorimetrically in the striatum of the isolated brain. The EEG was recorded by two symmetrical bipolar leads from the parietal regions at various times during the 30 min perfusion period and was stored on magnetic tape. The recordings were evaluated visually and quantitatively by automatic analysis. CPZ-NO was found to be the most active agent both in changing the EEG and in elevating the HVA level in the striatum. The mean EEG amplitude and the slow wave activity increased significantly. The increase of the HVA level in the striatum was correlated with the increase of delta waves as well as excess of kurtosis and skewness calculated from the amplitude histography data. The desmethylated metabolites caused only moderate central effects.

Animals↗
PubMed1979

Effect of intravenous diazepam on human lower oesophageal sphincter pressure under controlled double blind crossover conditions.

The effect of diazepam on the lower oesophageal sphincter (LOS) pressure is controversial. Therefore, a double-blind crossover study was performed on 18 healthy volunteers to determine the sphincter response to intravenous diazepam--70, 140, 280 microgram/kg, which correspond to a total dose of 5, 10, and 20 mg. respectively. After the 5 and 10 mg dose no signficant effect on LOS pressure could be observed when compared with placebo. After the 20 mg dose a significant rise in pressures (deltaPLOS) was recorded for 40 minutes with a maximum deltaPLOS of + 16.2 +/- 6.6 (mean +/- SEM) mmHg after 50 minutes (P less than 0.01) (46 +/- 1.3% increase above the basal pressure). It is concluded that diazepam does not affect lower oesophageal sphincter competence and therefore does not increase the risk of regurgitation and pulmonary aspiration in premedicated patients.

Adult↗
PubMed1979

Evaluation of the effect of domperidone on human oesophageal and gastroduodenal motility by intraluminal manometry.

Intraluminal manometry has been used in a series of five studies on healthy volunteers and patients, to examine the action of domperidone on lower oesophageal sphincter pressure (LOSP), on peristaltic contraction, amplitudes and on antral, pyloric and duodenal motility. Furthermore, the effect on gastric acid secretion, pH, secretory volume and serum gastrin levels was studied. It was found that domperidone increased LOSP significantly but was less effective in patients with symptomatic gastro-oesophageal reflux than in normal volunteers. The drug also increased the amplitude of oesophageal and duodenal peristalsis but had no effect on endogenous gastrin release or on gastric acid secretion. The results suggest that this drug may be useful in the treatment of gastro-oesophageal and gastroduodenal reflux. This potential benefit is enhanced by the absence of side effects even when given in high doses.

Adult↗
PubMed1978

[Anaesthesia and intracellular distribution of cerebral hexokinase (author's transl)].

The purpose of the present investigation was to demonstrate how the intracellular distribution of hexokinase was influenced by anaesthetics. The experiments were carried out using mice in vivo and the isolated perfused rat brain. Thiopentone (100 mg/kg i.p.) produced an increase of soluble hexokinase activity in brains of mice which were removed from the skull in 45 s to 120 s. A solubilization of hexokinase activity was demonstrable in the surgical stage of anaesthesia, when the animals awoke redistribution to control values was measurable. A dose dependent influence of thiopentone on hexokinase distribution was demonstrated in the isolated perfused rat brain. When the thiopentone concentration in the perfusion medium was increased (0.05-0.8 mM) the soluble hexokinase activity was elevated while the EEG activity was reduced up to isoelectricity.

Anesthetics↗
PubMed1977

Solubilization of brain mitochondrial hexokinase by thiopental.

The control of hexokinase activity probably is accomplished by regulating the partitioning of the enzyme between soluble and particulate forms, the latter being more active. In the present investigation we have examined the thiopental effect on the cerebral hexokinase distribution. In anesthesia, after administration of thiopental to male Sprague Dawley rats, the increase of the soluble fraction of hexokinase was dose dependent. The change in the intracellular hexokinase distribution was reversible and lasted as long as general anesthesia existed. Also in experiments in vitro a solubilization of the mitochondrial hexokinase by thiopental (0.1--1 mM) occurred; it was depending on drug concentration. An inhibition of hexokinase was found neither in the total brain extract, nor in the soluble or the particulate fraction. The results suggest that phosphorylation of glucose in brain may be suppressed in anesthesia by shifting hexokinase activity from a more active mitochondrial form to its less active soluble form. This effect seems to be caused by a direct action of thiopental and is obviously correlated with anesthesia.

Animals↗
PubMed1976

Decreased GABA and glutamate concentration in rat brain after treatment with 6-aminonicotinamide.

The effect of 6-aminonicotinamide (6-AN) on putative amino acid neurotransmitters, namely glutamate, GABA and aspartate was studied on brains of rats treated with this antimetabolite (35 mg/kg i.p.). After 6-AN application the following substrates and metabolites were determined: phosphocreatine, ATP, ADP, AMP, glucose, glucose 6-phosphate, fructose, glutamate, GABA, aspartate, ammonia, and 6-phosphogluconate. The alterations in the cerebral energy metabolism were found as reported in the literature (increased levels of glucose, glucose 6-phosphate, decreased levels of lactate and pyruvate) and could be interpreted as the result of a reduced glycolytic flux rate. After a prolonged period of 6-AN pretreatment (16-30 h) the GABA and glutamate concentrations were significantly reduced, whereas the level of aspartate remained unchanged. From the result presented the two following conclusions may be drawn: a) The changes in the concentration of neurotransmitters as GABA and glutamate could be responsible for some neurological symptoms produced by 6-AN. b) As 6-AN seems to affect the GABA-shunt it represents a model substance for studying this pathway in the nervous system.

6-Aminonicotinamide↗
PubMed1976

[Influence of diazepam and phenytoin on penicillin-induced cerebral convulsions (author's transl)].

The effects of diazepam and phenytoin on penicillin-induced EEG changes and convulsions were studied in 32 rabbits. EEG changes and convulsions were elicited by 2.4 g/kg benzylpenicillin i.v. over 50 min. The dosages of the anticonvulsants were 1, 5 and 10 mg of diazepam and 10, 20 and 30 mg/kg of phenytoin. The qualitative and semiquantitative evaluation of the electroencephalograms revealed no reduction of spike frequency or spike amplitude for either of the two drugs. However, in contrast to phenytoin, diazepam was highly effective in preventing the development of generalized convulsions. None of the 12 diazepam-treated animals developed a convulsion, whereas in most of the phenytoin treated animals and in most of the controls generalized convulsions appeared. The results suggest that diazepam should be used in the treatment of penicillin-encephalopathy.

Animals↗
PubMed1975

The effects of increased glucose supply and thiopental anesthesia on energy metabolism of the isolated perfused rat brain.

The effects of glucose concentrations in the perfusion medium ranging from 5 to 15 mM and thiopental, on cerebral energy metabolism were studied using the isolated perfused rat brain. After a perfusion time of 30 min brain levels of the following substrates and metabolites were determined: P-creatine, ATP, ADP, AMP, glycogen, glucose, glucose-6P, fructose-6-P, pyruvate, lactate, alpha-ketoglutarate, glutamate, ammonia. In control experiments increasing the glucose concentration in the perfusion medium produced an increase of intracellular brain glucose concentration only, revealing a linear relationship between glucose content in brain and blood. Neither high-energy phosphates nor glycolytic intermediates were markedly affected by the changes in blood glucose. With an anesthetic dose of thiopental (0.15 mM) in the perfusion medium identical metabolic alterations occured in all experiments: P-creatine and glucose were significantly increased whereas ADP, AMP, lactate and pyruvate were diminished. Also with thiopental brain glucose was linearly related with the glucose concentration in the perfusion medium. The calculated regression line was apparently parallel with that from control experiments; that means thipental always caused an elevation of brain glucose by the same amount of 0.9 mumoles/g--irrespective of the initial cerebral glucose content. The results yield further evidence that glucose transport is not the rate-limiting step in glycolysis. The action of thiopetal on glycolytic pathway is discussed.

Adenine Nucleotides↗
PubMed1975

Decreased glycolytic flux rate in the isolated perfused rat brain after pretreatment with 6-aminonicotinamide.

Cerebral energy metabolism was studied in the isolated perfused rat brain after 6-aminonicotinamide (6-AN; 35 mg/kg i.p.) administered to the intact animals 7 hrs before perfusion was started. The metabolic alterations in the isolated rat brains were such as reported for rat and mouse brain in vivo: Inhibition of 6-phosphogluconate dehydrogenase was followed by an accumulation of 6-phosphogluconate, leading to a decreased activity of glucosephosphate isomerse. This was reflected by increased levels of glucose and glucose 6-phosphate and decreased levels of fructose 6-phosphate, pyruvate and lactate. Since the concentration of lactate in the perfusate of the isolated brain was also lowered, 6-AN must have reduced the glycolytic flux rate.

6-Aminonicotinamide↗