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J Krieglstein

Publications and source records attributed to J Krieglstein.

At least 163 records · Page 9Linked to original sources
PubMed1985

Effect of gallopamil on energy metabolism of the isolated perfused rat brain in the postischemic period.

The isolated perfused rat brain was used to demonstrate an effect of gallopamil on energy metabolism affected by ischemia. After a perfusion period of 30 min and 10 min of ischemia the isolated brain preparation was reperfused. From the onset of perfusion onwards, gallopamil (1 or 10 mumol/l) was present in the medium. The higher concentration of gallopamil accelerated significantly the restoration of the high-energy phosphates in the recovery stage: after 2 min of recirculation the ATP and the creatine-P levels were higher and the AMP level was lower in cortical tissue of drug-treated brains than in untreated controls. These results suggest that gallopamil protected brain energy metabolism against ischemic damage.

Adenosine Monophosphate↗
PubMed1984

Effect of an extract of Ginkgo biloba on rat brain energy metabolism in hypoxia.

The purpose of the present investigation was to determine brain energy metabolism under hypoxic conditions as influenced by an extract of Ginkgo biloba (EGB). Male Sprague-Dawley rats treated with EGB were exposed to hypobaric or hypoxic hypoxia, and at various time points during or after hypoxia the levels of high-energy phosphates and some substrates of glycolysis were measured in brain cortical tissue. Rats treated with EGB (100 mg/kg, intraperitoneally) survived hypobaric hypoxia for a much longer period than controls (e.g. controls: 3.9 +/- 1.8 min, EGB-treated: 23.6 +/- 10.5 min). The brain glucose level was elevated by EGB in most experimental series, and the lactate concentration was slightly lower than in control brains. The lowering of lactate/pyruvate ratio was due to the decreased level of lactate and to the enhanced concentration of pyruvate as well. When hypoxia was sufficiently severe the breakdown of high-energy phosphates was less pronounced in EGB-treated animals. After oral application of EGB for 14 days the rats survived hypobaric hypoxia for 25.7 +/- 2.5 min whereas controls survived for 11.5 +/- 5.1 min. However, brain energy metabolism was not significantly influenced by this oral treatment. It is suggested that changes in brain energy metabolism and blood flow may contribute to the protective effect of EGB against hypoxia.

Animals↗
PubMed1984

Comparison of rat brain and heart mitochondrial hexokinase solubilized by methohexital.

The purpose of the present investigation was to compare the solubilizing effect of methohexital on the mitochondrially bound hexokinase activity in brain and heart tissue of the rat. Experiments were performed using intact rats, the isolated perfused rat brain and heart as well as mitochondrial fractions from rat brain and heart tissue. It was shown that bound hexokinase activity was significantly solubilized by methohexital in brain tissue in vivo and in the isolated perfused rat brain but no effect was demonstrable in heart tissue. When mitochondrial fractions were incubated with methohexital in vitro, hexokinase activity was significantly solubilized from brain mitochondria but only slightly from heart mitochondria although glucose-6-phosphate was able to displace hexokinase also from heart mitochondria. The results suggest that mitochondrially bound hexokinase activity in brain tissue is particularly sensitive against the solubilizing effect of anesthetics. This effect could contribute to the sensitivity of brain function and metabolism against anesthetic drugs.

Animals↗
PubMed1984

Effect of dihydroergocristine on energy metabolism studied in the isolated perfused rat brain affected by ischemia and in neuroblastoma cells deprived of oxygen and glucose.

The effect of dihydroergocristine on energy metabolism was studied in the isolated perfused rat brain affected by ischemia and in cultivated C-1300 neuroblastoma cells deprived of oxygen and glucose. Creatine phosphate, ATP, ADP, AMP, glucose, glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, pyruvate, and lactate were measured enzymatically. After a perfusion period of 30 min, the cortex of the isolated perfused rat brain exhibited an energy state not different from that in vivo. Dihydroergocristine added to the perfusion medium (5 mumol/L) did not influence these substrate levels under normal perfusion conditions. However, this drug was able to retard the breakdown of high-energy phosphates during ischemia and to accelerate the restoration of the energy state during the postischemic reperfusion period. The perfusion rate was not changed by the drug, and therefore it was assumed that dihydroergocristine could act directly on cell metabolism. This view was supported by the results obtained from experiments using cultivated N-2a neuroblastoma cells. These cells were incubated in a buffered salt solution deprived of glucose and oxygen for 15 min. Under these conditions, dihydroergocristine (2 mumol/L) added to the incubation medium caused changes in the concentrations or the high-energy phosphates similar to those in the isolated brain preparation: It increased the ATP concentration and decreased the ADP concentration significantly.

Adenosine Triphosphate↗
PubMed1984

P-31 nuclear magnetic resonance analysis of brain: II. Effects of oxygen deprivation on isolated perfused and nonperfused rat brain.

Phosphatic metabolite (perchloric acid extractable) concentrations of cerebral tissues were analyzed by phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy following external perfusion of the isolated rat brain (30 min or 60 min) under the following conditions: (a) constant perfusion pressure with either fluorocarbon- or erythrocyte-based medium, and (b) constant perfusate flow rate (3 ml/min) with the erythrocyte-based medium. Metabolite concentrations of control perfused brains were compared with those in nonperfused controls to provide a basis for detecting any qualitative or quantitative changes in cerebral metabolite composition. Metabolic responses of perfused brains to ischemia (incomplete ischemia, 83% reduction in flow for 10 min; transient complete ischemia for 1.5 or 2 min) were evaluated immediately after the ischemic episode and at selected time points during reperfusion (3 and 15 min). Alterations in cerebral metabolite levels induced by hypoxia were analyzed using a nonperfused rat brain model. Irrespective of the perfusion method employed, the phosphatic metabolites of control perfused rat brains were identical quantitatively to those of the nonperfused controls. Cerebral ischemia resulted in significantly increased levels of ADP, AMP + IMP, Pi, fructose 1,6-diphosphate, and glycerol 3-phosphate (global ischemia only), whereas ATP and phosphocreatine (PCr) levels declined significantly. The magnitude of these changes varied with the severity of the ischemia; however, following 15 min of control reperfusion metabolite levels had reverted to preischemic values. Significant perturbations in tissue phosphoethanolamine (3.84 delta resonance) content were evident at various time points during ischemia and postischemic recovery, which varied according to the perfusion conditions. In contrast to the changes observed in response to ischemia, hypoxia affected only cerebral high-energy phosphate levels. ATP and PCr levels were reduced, while a concomitant, essentially equimolar, increase in Pi and ADP was observed. The present studies indicate that in terms of phosphatic metabolites, the control equilibrated isolated perfused rat brain is quantitatively and qualitatively indistinguishable from the nonperfused rat brain in vivo regardless of the perfusion conditions (constant flow versus constant pressure). The metabolic responses to ischemia and hypoxia, as measured by P-31 NMR, were consistent with the pattern of changes reported elsewhere. Overall, P-31 NMR spectroscopic evaluation of the intact rat brain provides a potential experimental context for dynamic measures of cerebral metabolism under exogenously controlled conditions. Th

Animals↗
PubMed1984

[The hypotensive effect of aromatic amidines and imidazolines].

Some amidine, diamidine and diimidazoline derivatives were tested on their ability to lower the blood pressure of the rat. Except for 5-amidino-2-phenylindole (271/179) all substances led to a short-lasting hypotension, the dose relationship of some of which was investigated. The biscationic character was a prerequisite for a strong hypotensive action. The predominantly peripheral origin of the blood pressure lowering action was shown for the substances pentamidine, diminazene, 6-amidino-2- (4-amidinophenyl)-indole (102/198), 5-amidino-2-(4-amidinophenyl) - benzofurane (150/49) and 2,6-diamidinoindole (261/115). A parasympathomimetic and histaminic efficiency could be excluded. The pressor effect of norepinephrine (noradrenaline) was reduced under the influence of pentamidine, diminacene and 102/198. With the dog 102/198 and 261/115 showed a diminution of heart rate and force as well as a vasodilatory effect. Using the rat, different cardiovascular parameters behaved analogous. Pentamidine, diminazene, 102/198 and 261/115 increased the force of contraction of the isolated rat atrium. Toxic effects were observed in doses as high as 0,5 mmol/l and l mmol/l. Pentamidine reduced the heart rate of the isolated atrium in a dose-dependent manner. Taking into account the in vitro results, the heart effects were interpreted as being reflectory. In the isolated rat aorta preparation the aforementioned substances in low doses shifted the dose-response curves of norepinephrine to the right, whereas higher doses also reduced the maximum contraction. Considering the results on the intact animal, a direct action of the diamidines on vascular smooth muscle was discussed.

Amidines↗
PubMed1984

[The effects of valtrate on the EEG of the isolated, perfused rat brain].

The purpose of the present investigation was to prove the central activity of valtrate. In order to avoid biotransformation of valtrate the isolated perfused rat brain was used for this study. The CNS activity of the drug was characterized by EEG changes which were analysed visually and quantified by automatic methods. The following results were obtained: In the EEG of brains perfused with valtrate the normal background beta activity was interrupted by spikes and paroxysmal patterns of theta frequencies. These patterns disappeared after reperfusion with the control medium without drug. Valtrate reduced the beta activity and produced an increase in the theta and delta frequencies of the EEG. Using valtrate concentrations of 0.1-100 mumol/l in the perfusion medium a clear dose-response relationship was not demonstrable.

Animals↗
PubMed1984

[Comparison of the effects of piracetam and methohexital on cerebral energy metabolism].

Several authors suggest an influence of piracetam on brain energy metabolism. Therefore, we examined the effect of this drug on the levels of high-energy phosphates, glucose, some metabolites of glycolysis and free amino acids in the rat brain under normoxic, ischemic and postischemic conditions. In order to eliminate peripheral effects on the cerebral metabolism the isolated perfused rat brain was used as a model for this study. Methohexital was also administered for demonstrating protective effects on energy metabolism under the experimental conditions employed. The barbiturate, not piracetam, reduced the recovery time of the EEG after 1.5 or 2 min of ischemia. The depletion of energy reserves after the ischemic periods was diminished by methohexital but not by piracetam. The substrate and metabolite levels removed faster to the control levels under methohexital in the postischemic period whereas the piracetam treated brains did not differ from the controls. The subchronical treatment of rats in vivo with piracetam only caused a slightly smaller increase in the cerebral lactate concentration after anoxic periods. These results do not suggest an acute effect of piracetam on rat brain energy metabolism whereas the barbiturate methohexital may protect the brain against ischemic damage in a certain extent.

Amino Acids↗
PubMed1983

[Pharmacology of potential antidepressants of the N-L-phenylalanyl-beta-phenylalkylamine class].

The spectrum of the pharmacological activities of N-L-phenylalanyl L-2-amino-1-phenylpropane (13), the most active representative of the investigated L-N-phenylalanyl-beta-phenylalkylamines 11-20, comprises adrenergic (noradrenaline potentiation on the vas deferens of the rat, tetrabenazine antagonism in the mouse), as well as cholinergic blocking (acetylcholine antagonism on the jejunum of the rat, oxotremorine antagonism in the mouse, anti-aggressive activity in isolated mice) and localanesthetic properties (inhibition of conduction in the ventricular strip of the frog heart) as described for antidepressants. In its pharmacological behavior 13 meets rather an antidepressant than a psychotonic drug. The conception of a partial metabolic liberation of the latent amphetamine component in 13 and a certain contribution of amphetamine to the effect of 13 is supported by the fact that at higher dosages a shortening of the hexobarbital narcosis and an increase of the spontaneous activity in mice is seen.

Animals↗
PubMed1982

Relationship between brain mitochondrial hexokinase and neuronal function: comparable effects of 2-deoxy-D-glucose and thiopental.

Mitochondrially bound brain hexokinase is solubilized by anesthetics and this effect has been suggested to contribute to anesthesia. In the present investigation the influence of the metabolic inhibitor 2-deoxy-D-glucose (2-DOG) was studied. An isolated rat brain preparation was used to avoid the contribution of peripheral reactions. Isolated rat brains were perfused for 45 min with media containing 4 mmol/l glucose, 10 mmol/l 2-DOG and/or 0.4 mmol/l thiopental. The EEG was monitored and acetylcholine, 2-DOG and its 6-phosphate, as well as the intracellular distribution of hexokinase activity were determined in brain tissue. Soluble hexokinase activity in brain cortex was enhanced by 2-DOG, as also by thiopental, and even more pronounced by both drugs used together, Results from in vitro experiments suggest that solubilization of mitochondrial hexokinase after 2-DOG is mediated by intracellularly accumulated 2-DOG-6-phosphate. 2-DOG produced a significant impairment of neuronal activity, revealing EEG patterns similar to those caused by thiopental anesthesia. Cortical acetylcholine levels were elevated by 2-DOG, as well as by thiopental, and again both drugs showed an additive effect when used in combination. This effect which may be the result of an inhibition of acetylcholine release, was also detectable in mice in vivo after 5 g 2-DOG/kg i.p., whereas the same dose of 3-O-methylglucose had no effect. The results provide further evidence that mitochondrial hexokinase may be involved in the relationship between cerebral metabolism and brain function.

Animals↗
PubMed1982

Solubilization of hexokinase activity by an effect of thiopental on the mitochondrial membrane.

In thiopental anesthesia of rats cerebral mitochondrial hexokinase activity was solubilized. This solubilization was also observed when the period necessary for the removal of the rat brain was shortened to 15 s by brain blowing. The influence of the drug on the binding of hexokinase activity to mitochondria of brain, liver and neuroblastoma cells was studied in vitro. Solubilization of hexokinase activity was achieved in all systems at therapeutically relevant thiopental concentrations. On the other hand, chlorpromazine as a highly lipophilic drug only solubilized hexokinase activity at concentrations being already lytic to the membrane. Thus, it is concluded that thiopental solubilize hexokinase activity by affecting the mitochondrial membrane, and that this effect is not only dependent on the lipophilic character of a drug.

Anesthesia↗
PubMed1982

[Mechanisms of the protective effect of methohexital on cerebral energy metabolism].

The purpose of the present investigation was to study the effect of alpha-(+/-)-5-allyl-1-methyl-5-(1-methyl-2-pentinyl) barbituric acid (methohexital, Brevimytal sodium) on brain energy metabolism. The model of the isolated perfused rat brain was used. The high-energy phosphates, some substrates of glycolysis and the intracellular distribution of hexokinase activity were measured in the cortical tissue of the isolated rat brain after 30 min of perfusion, after ischemia or anoxia and after various recovery periods. The EEG was recorded as a parameter of the neuronal activity. The following results were obtained: 1. Ischemia and anoxia accelerated the glycolysis rate which was inhibited by methohexital. 2. The energy metabolism was more rapidly normalized after ischemia or anoxia when methohexital was added to the perfusion medium (0.2 mmol/l). 3. Compared to the corresponding preparation, the spontaneous electrical activity of the isolated brain was maintained in ischemia or anoxia for a longer period and appeared again more rapidly in the recovery periods when methohexital was present. 4. Phosphofructokinase activity was inhibited by methohexital in the recovery period after ischemia or anoxia, respectively. 5. Inhibition of hexokinase activity predominated in the surgical stage of anesthesia when glycolysis rate was not accelerated. Methohexital seemed to inhibit hexokinase activity by solubilizing the mitochondrial bound form.

Adenosine Triphosphate↗
PubMed1981

Effects of thiopental on regulatory mechanisms of brain energy metabolism.

After administration of thiopental to artificially ventilated rats, the EEG, cerebral metabolism, intracellular distribution of hexokinase activity and the thiopental concentration in brain was measured. Considering the EEG changes, the time course of thiopental action was divided into an initial stage with increased beta activity and a following second stage with reduced beta activity. The glucose-6-phosphate concentration significantly increased in the first stage and fell again to the control level with the beginning of the second stage. Furthermore, during the second stage the glucose level increased and the hexokinase activity shifted from the mitochondrially bound form to the soluble form. From these results the following conclusions were drawn: Phosphofructokinase activity appeared inhibited only during the initial stage. During the second stage comparable to the stage of surgical anesthesia, thiopental solubilizes bound hexokinase activity inhibiting thereby energy metabolism.

Amino Acids↗
PubMed1981

Influence of thiopental on intracellular distribution of hexokinase activity in various tumor cells.

In earlier work it has been shown that mitochondrially bound brain hexokinase is solubilized by anesthetics. This effect was reevaluated using cultured cells. For the present experiments Ehrlich ascites, Harding-Passey melanoma, C-1300-neuroblastoma and C-6-glioma cells were used. The great portion of hexokinase activity bound to the mitochondria of these cells was similar to that in rat brain. After incubation with thiopental the soluble hexokinase activity was increased in all cells studied. Using neuroblastoma and glioma cells the thiopental effect was demonstrated to be dose-dependent. Thus, cultured tumor cells seem to be useful for studying the relationship of the intracellular distribution of hexokinase activity, energy metabolism and the effect of anesthetics.

Cell Division↗
PubMed1980

Fluorocarbon perfusion medium applied to the isolated rat brain.

In order to overcome the disadvantages of erythrocytes and albumin, a totally synthetic medium for the perfusion of the isolated rat brain was developed. the perfusion medium was based upon Krebs-Henseleit solution and contained in addition a fluorocarbon (FC 43) for oxygen transport and a polyol (Pluronic F 68) to furnish emulsifying and oncotic properties. The physico-chemical properties of this fluorocarbon perfusion medium allowed perfusion of an isolated rat brain to continue for more than 7 hr, while the medium could be stored as a stock emulsion for several months. The appropriate function of the isolated perfused rat brain is demonstrated by the EEG and by various substrates of the energy metabolism. The suitability of the fluorocarbon medium for perfusion of an isolated rat brain preparation is discussed.

Animals↗