Effect of barbitone sodium and thiopental sodium on brain dopamine, noradrenaline, serotonin and 5-hydroxyindoleacetic acid content in Arvicanthis niloticus

The quantitative estimation of total dopamine (DA), noradrenaline (NE), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) content in the whole brain tissue of normal Nile grass rat, Arvicanthis niloticus, gives and average of 631 +/- 12 ng DA/g, 366 +/- 12 ng NE/g, 617 +/- 15 ng 5-HT/g and 431 +/- 10 ng 5-HIAA/g fresh brain tissue. The effect of barbitone sodium and thiopental sodium on the total DA, NE, 5-HT and 5-HIAA content in the brain tissue of the Nile grass rat, Arvicanthis niloticus, was studied. The total DA, NE, 5-HT and 5-HIAA contents were determined 5 hr after i.p. injection of different doses of barbitone sodium (20, 40 and 80 mg/ml/100 g body wt) and thiopental sodium (5, 10 and 20 mg/ml/100 g body wt). The effect of different time intervals (1, 10, 30 min, 1, 2.5, 5, 8, 16, 24 and 48 hr) on the total brain DA, NE, 5-HT and 5-HIAA content was investigated after i.p. injection of 40 mg of barbitone sodium and 10 mg of thiopental sodium/ml/100 g body wt. Both barbitone sodium and thiopental sodium caused an increase in DA, NE and 5-HT content and a decrease in 5-HIAA content in the brain tissue of Arvicanthis niloticus. The increase in the whole brain contents of DA, NE and 5-HT after the administration of barbitone sodium and thiopental sodium may be due either to inhibition of transmitter release by an action at the monoamine nerve terminal or to effects causing a decrease in nerve impulse flow. On the other hand, the decrease in 5-HIAA may be due to the decrease in the turnover of 5-HT.     

Thiopental inhibits nitric oxide production in rat aorta

We studied whether thiopental affects endothelial nitric oxide dependent vasodilator responses and nitrite production (an indicator of nitric oxide production) elicited by acetylcholine, histamine, and A23187 in rat aorta (artery in which nitric oxide is the main endothelial relaxant factor). In addition, we evaluated the barbiturate effect on nitric oxide synthase (NOS) activity in both rat aorta and kidney homogenates. Thiopental (10-100 microg/mL) reversibly inhibited the endothelium-dependent relaxation elicited by acetylcholine, histamine, and A23187. On the contrary, this anesthetic did not modify the endothelium-independent but cGMP-dependent relaxation elicited by sodium nitroprusside (1 nM - 1 microM) and nitroglycerin (1 nM - 1 microM), thus excluding an effect of thiopental on guanylate cyclase of vascular smooth muscle. Thiopental (100 microg/mL) inhibited both basal (87.8+/-14.3%) and acetylcholine- or A23187-stimulated (78.6+/-3.9 and 39.7+/-5.6%, respectively) production of nitrites in aortic rings. In addition the barbiturate inhibited (100 microg/mL) the NOS (45+/-4 and 42.8+/-9%) in aortic and kidney homogenates, respectively (measured as 14C-labeled citrulline production). In conclusion, thiopental inhibition of endothelium-dependent relaxation and nitrite production in aortic rings strongly suggests an inhibitory effect on NOS. Thiopental inhibition of the NOS provides further support to this contention.     

Anaphylaxis due to thiopental sodium anesthesia.

Anaphylaxis due to an anesthetic is one type of cardiovascular emergency that can occur during general anesthesia. Anaphylactic reactions to muscle relaxants have been documented. Barbiturates, used as sedatives, are well known to produce cutaneous reactions, but anaphylaxis after their ingestion seems to be rare. Generalized allergic reactions to thiopental sodium during anesthesia are mentioned in the product monograph for Penthothal sodium, and rare case reports of anaphylactic reactions to infused thiopental have appeared, generally in the anesthesiology literature. Documentation of the immunologic responses to thiopental sodium has been limited to the demonstration of an allergic reaction to thiopental by skin testing in some cases. This report describes a woman who, after having tolerated thiopental sodium and other general anesthetics, became sensitive to this agent and had a severe acute reaction at the time of induction of general anesthesia.     

Determination of thiopental in urine sample with high-performance liquid chromatography using iodine-azide reaction as a postcolumn detection system

The reaction between iodine and azide ions induced by thiopental was utilized as a postcolumn reaction for chromatographic determination of thiopental. The method is based on the separation of thiopental on an Nova-Pak CN HP column with an acetonitrile-aqueous solution of sodium azide as a mobile phase, followed by spectrophotometric measurement of the residual iodine (lambda=350 nm) from the postcolumn iodine-azide reaction induced by thiopental after mixing an iodine solution containing iodide ions with the column effluent containing azide ions and thiopental. Chromatograms obtained for thiopental showed negative peaks as a result of the decrease in background absorbance. The detection limit (defined as S/N=3) was 20 nM (0.4 pmol injected amount) for thiopental. Calibration graphs, plotted as peak area versus concentrations, were linear from 40 nM. The elaborated method was applied to determine thiopental in urine samples. The detection limit (defined as S/N=3) was 0.025 nmol/ml urine. Calibration graphs, plotted as peak area versus concentrations, were linear from 0.05 nmol/ml urine. Authentic urine samples were analyzed, thiopental was determined at nmol/ml urine level.     

Effect of thiopental sodium and barbitone sodium on the total acetylcholine content and acetylcholinesterase activity in the brain tissue of Arvicanthis niloticus

The total ACh content and AChE activity were determined 1 hr after the i.p. injection of different doses of thiopental sodium (5, 10 and 20 mg/ml/100 g body wt) and barbitone sodium (20, 40 and 80 mg/ml/100 g body wt). The effect of different time intervals (1 min, 10 min, 30 min, 1 hr, 2.5 hr, 5 hr, 8 hr, 12 hr, 24 hr and 48 hr) on the total ACh content and AChE activity was investigated after i.p. injection of 10 mg thiopental sodium and 40 mg barbitone sodium/ml/100 g body wt. Both thiopental sodium and barbitone sodium increased the total ACh content in the brain tissue of Arvicanthis niloticus. Both drugs inhibited the brain AChE activity. It is thought that the increase in the total ACh content in the brain tissue of Arvicanthis niloticus may be due to a decrease in the release of ACh from the neuronal tissue and a decrease in AChE activity.     

Cytogenetic effect of barbiturate anesthetizing substances in a human peripheral blood leukocyte culture

It is found that hexenal and sodium thiopental in vitro produced a two-fold increase of frequency of chromosome aberrations as compared with the control and this effect was not dose-dependent. The anesthetics under study affected in vitro 3H-thymidine incorporation into DNA of lymphocytes, and a ten-fold hexenal dose intensified 3H-thymidine incorporation. The frequency of chromosome aberrations in vivo was at the level of the spontaneous mutation after use of sodium thiopental and slightly increased hexenal.     

General anesthesia in pigs.

Conventional swine weighing 20-45 kg were anesthetized for surgical procedures. After fasting for 24 hours, ketamine hydrochloride and xylazine were administered intramuscularly. Following tracheal intubation, sodium thiopental was administered via the aural or femoral vein.     

Comparison of different anaesthetic methodologies for sedation during in vitro fertilization procedures: effects on patient physiology and oocyte competence

The main goal of the present retrospective study is to compare four analgesic methodologies (EMLA cream, propofol, thiopental sodium, sevoflurane) for in vitro fertilization (IVF) oocyte retrieval. We found that most anaesthetic parameters were not significantly different among all treatments. In contrast, significant differences were revealed in all groups for total number of oocytes retrieved per patient, rate of mature oocytes at metaphase II stage (MII) and percentage of fertilization and embryo development. In the EMLA cream and thiopental sodium groups we observed the highest percentage of MII oocytes (P < 0.001). Fertilization rate in the EMLA and sevoflurane groups were similar but significantly higher than the propofol and thiopental sodium groups (P < 0.001). The highest rate of anomalous fertilization was observed in the propofol group. Rate of embryo development was similar in all groups but sevoflurane group had a lower percentage of good embryos. In conclusion, by comparing different anaesthetic techniques with different mechanisms of action and administration, potential negative effects of these drugs on the initial stages of human IVF procedure were revealed. Therefore, a local anaesthetic cream is proposed as an acceptable alternative option for anaesthesia during transvaginal oocyte retrieval.     

Thiopental and ether anaesthesia decrease the prostaglandin receptor density of the rat liver.

Male Sprague-Dawley rats were killed either by decapitation or during anaesthesia with thiopental or diethylether by aortectomy. Livers were removed and liver plasma membranes were prepared using standard techniques. Direct binding experiments with 3H-PGE1 and 3H-iloprost revealed heterogeneity of the binding sites (high and low affinity binding sites), whereas 3H-PGE2 demonstrated only high affinity binding to the liver. The highest binding capacity for all radioligands was found for livers after decapitation. Livers obtained during anaesthesia showed a significantly (p less than 0.05 to p less than 0.001) lower binding capacity and binding affinity for 3H-PGE1, 3H-PGE2 and 3H-iloprost. The reduction in binding activity was more pronounced in livers obtained during inhalation than thiopental anaesthesia. Specific binding amounted to 82.1 +/- 7% for 3H-PGE2, 75.3 +/- 9% for 3H-PGE1 and 78.9 +/- 8% for iloprost in livers obtained after decapitation. In livers obtained during anaesthesia specific prostaglandin binding was significantly (p less than 0.01) decreased, again being more pronounced during inhalation than thiopental anaesthesia. These results suggest that some anaesthetics interfere with prostaglandin receptors of the liver.     

Relationship between extra and intracellular sources of calcium and the contractile effect of thiopental in rat aorta

To evaluate the relationship between the vasocontractile effect of thiopental and the extra and intracellular sources of Ca2+, we analyzed both the contractile effect of the barbiturate on rat aortic rings and its ability to modify the intracellular calcium concentration in cultured rat aorta smooth muscle cells. Thiopental (10-310 microg/mL) contracted aortic rings only in the presence of extracellular Ca2+, and this effect was not blocked by verapamil or diltiazem. On the contrary, Ca2+ (0.1-3.1 mM) evoked contractions only when thiopental (100 microg/mL) was present. Although in calcium-free solution thiopental (100 microg/mL) did not contract aortic rings, it abolished the contractile effect of either phenylephrine (10(-6) M) or caffeine (10 mM). Finally, thiopental augmented the intracellular calcium concentration in cultured smooth muscle cells incubated either in the presence or absence of calcium. In conclusion, thiopental's vasocontractile effect depends on extracellular calcium influx, which is independent of L-calcium channels. The increase in intracellular Ca2+ concentration elicited by thiopental in Ca2+-free solution and its ability to block the effect of phenylephrine and caffeine suggest that this barbiturate can deplete intracellular pools of calcium. Therefore, the calcium entry pathway associated with the contractile effect of thiopental may correspond to the capacitative calcium entry model.     

The effect of general anesthesia on memory in experimental animals

Full recovery of short-term memory (maximum time of delayed reactions) and of the structure of situational conditioned reflex and differentiation inhibition in dogs is observed in 1.5-2.5 h after tranquil-anaesthesia (diazepam-ketamine in doses of 0.3-15 mg/kg correspondingly) and dissociative anaesthesia by ketamine (15 mg/kg) in 6-8 h after neuroleptanalgesia (droperidol-fentanyl 2.5-0.05 mg/kg correspondingly), 20-24 h after narcosis by thiopental sodium (30 mg/kg) and by the end of the 3d day after neuroleptanaesthesia (droperidol-ketamine 2.5-15 mg/kg correspondingly). The recovery of the reaction of memory trace reproduction (of conditioned reaction of passive avoidance in rats) after various types of general anaesthesia is observed mainly in the same sequence, but on the average a day later than the short-term memory in dogs.     

Cyclic nucleotides (cAMP and cGMP) in the dog plasma during extracorporeal hemocarboperfusion

The concentrations of cyclic nucleotides (cAMP and cGMP) were measured in blood plasma of dogs subjected to extracorporeal hemocarboperfusion. In spite of complete and irreversible absorption of cyclic nucleotides by the coal absorbent, SKN-2M, the concentration of cGMP in plasma remained within normal. The concentration of cAMP increased 1.5-2.5-fold. The rise in the cAMP concentration was not connected with injection of sodium thiopental and heparin before hemocarboperfusion. It is assumed that cyclic nucleotides play the role of circulating intercellular regulators in blood plasma. These regulators are necessary for the normal course of metabolic processes.     

Detection of mercaptopyridines and mercaptopyrimidines in planar chromatography with iodine-azide reaction as a detection system

Reaction between iodine and azide ion induced by mercaptopyridines and mercaptopyrimidines was utilized as a detection system in TLC and HPTLC. The developed plates were sprayed with a freshly prepared mixtures of sodium azide and starch solution adjusted to pH 5.5, and exposed to iodine vapour. The spots became visible as white spots on violet-grey background. The iodine-azide detection system has been proved to be the most favourable and enabled to detect quantities per spot in the range of 1-20 pmol (HPTLC) and 1-60 pmol (TLC). The iodine-azide tests were compared with other visualizing techniques commonly used in planar chromatography (iodine vapour and UV254). The developed method was applied to detection of thiopental in biological samples.     

Experimental substantiation of the method of pharmaco-metabolic brain protection against hypoxia in severe craniocerebral injury]

The experiment has shown that a complex of functionally related vitamins including thiamine, lipoate, D-pantothenate, nicotinate and riboflavine in "pyruvate-dehydrogenase" ratios decreases inhibition of the activity of alpha-keto acid dehydrogenases in the brain and liver with thiopental anesthesia, intensifies arrival of [35S]-lipoate to the brain and decreases acute toxicity of sodium thiopental (TnNa). The same complex (where thiamine, pantothenate and riboflavine are substituted by the corresponding coenzyme forms) complemented by the components stimulating the function of GABA-bypath of the brain as administered to rats with serious craniocerebral injury on the background of prolonged anaesthesia effect improves recovery of the brain functions, that is followed by normalization of ketoglutarate-dehydrogenase activity, maintenance of GABA-bypath function and by a decrease of GABA and glutamate content in the brain. The results obtained substantiate the advisability to use vitamin-coenzyme-metabolic complex in the acute period of traumatic brain disease aimed to increase efficiency of the antihypoxic TnNa effect and to correct its undesirable effects.     

Myocardial uptake of thiopental enantiomers by the isolated perfused rat heart

Myocardial uptake of thiopental enantiomers by an isolated perfused rat heart preparation was examined after perfusion with protein-free perfusate. Outflow perfusate samples were collected at frequent intervals for 20 min during single-pass perfusion with 10 μg/ml racemic thiopental (washin phase) and for another 45 min during perfusion with drug-free perfusate (washout phase). (+)- and (−)-thiopental concentrations were assayed by chiral high-performance liquid chromatography. Heart rate, perfusion pressure, and electrocardiogram were also monitored. During the washin phase, there was no significant difference between the mean values of the equilibration rate constants of (+)- and (−)-thiopental enantiomers (0.44 ± 0.07 min⁻¹ and 0.43 ± 0.09 min⁻¹, respectively, P > 0.05). Mean volumes of distribution of (+)- and (−)-thiopental enantiomers were similar (6.34 ± 1.20 and 6.45 ± 1.29 ml/g for the washin phase and 7.22 ± 0.71 and 7.47 ± 0.81 ml/g for the washout phase, respectively, P > 0.05). This indicates that tissue accumulation of thiopental enantiomers in the isolated perfused rat heart was not stereoselective. Uptake of thiopental by the heart was perfusion flow rate-limited and independent of capillary permeability. These findings suggest that myocardial tissue concentration of racemic thiopental should be an accurate predictor of myocardial drug effect. © 1996 Wiley-Liss, Inc.     

Effects of thiopental on transport and metabolism of glutamate in cultured cerebellar granule neurons

This study was performed to analyze the effects of the barbiturate thiopental on neuronal glutamate uptake, release and metabolism. Since barbiturates are known to bind to the GABA(A) receptor, some experiments were carried out in the presence of GABA. Cerebellar granule neurons were incubated for 2 h in medium containing 0.25 mM [U-(13)C]glutamate, 3 mM glucose, 50 microM GABA and 0.1 or 1 mM thiopental when indicated. When analyzing cell extracts, it was surprisingly found that in addition to glutamate, aspartate and glutathione, GABA was also labeled. In the medium, label was observed in glutamate, aspartate and lactate. Glutamate exhibited different labeling patterns, indicating metabolism in the tricarboxylic acid cycle, and subsequent release. A net uptake of [U-(13)C]glutamate and unlabeled glucose was seen under all conditions. The amounts of most metabolites synthesized from [U-(13)C]glutamate were unchanged in the presence of GABA with or without 0.1 mM thiopental. In the presence of 1 mM thiopental, regardless of the presence of GABA, decreased amounts of [1,2, 3-(13)C]glutamate and [U-(13)C]aspartate were found in the medium. In the cell extracts increased [U-(13)C]glutamate, [1,2, 3-(13)C]glutamate, labeled glutathione and [U-(13)C]aspartate were observed in the 1 mM thiopental groups. Glutamate efflux and uptake were studied using [(3)H]D-aspartate. While efflux was substantially reduced in the presence of 1 mM thiopental, this barbiturate only marginally inhibited uptake even at 3 mM. These results may suggest that the previously demonstrated neuroprotective action of thiopental could be related to its ability to reduce excessive glutamate outflow. Additionally, thiopental decreased the oxidative metabolism of [U-(13)C]glutamate but at the same time increased the detectable metabolites derived from the TCA cycle. These latter effects were also exerted by GABA.     

Propofol and thiopental attenuate adenosine triphosphate-sensitive potassium channel relaxation in pulmonary veins

Pulmonary veins (PV) make a significant contribution to total pulmonary vascular resistance. We investigated the cellular mechanisms by which the intravenous anesthetics propofol and thiopental alter adenosine triphosphate-sensitive potassium (KATP+) channel relaxation in canine PV. The effects of KATP+ channel inhibition (glybenclamide), cyclooxygenase inhibition (indomethacin), nitric oxide synthase inhibition (L-NAME), and L-type voltage-gated Ca2+ channel inhibition (nifedipine) on vasorelaxation responses to levcromakalim (KATP+ channel activator) alone and in combination with the anesthetics were assessed. The maximal relaxation response to levcromakalim was attenuated by removing the endothelium and by L-NAME, but not by indomethacin. Propofol (10(-5), 3x10(-5), and 10(-4) M) and thiopental (10(-4) and 3x10(-4) M) each attenuated levcromakalim relaxation in endothelium-intact (E+) rings, whereas propofol (3x10(-5) and 10(-4) M) and thiopental (3x10(-4) M) attenuated levcromakalim relaxation in endothelium-denuded (E-) rings. In E+ rings, the anesthesia-induced attenuation of levcromakalim relaxation was decreased after pretreatment with L-NAME but not with indomethacin. In E-strips, propofol (10(-4) M) and thiopental (3x10(-4) M) inhibited decreases in tension and intracellular Ca2+ concentration ([Ca2+]i) in response to levcromakalim, and these changes were abolished by nifedipine. These findings indicate that propofol and thiopental attenuate the endothelium-dependent component of KATP+ channel-induced PV vasorelaxation via an inhibitory effect on the nitric oxide pathway. Both anesthetics also attenuate the PV smooth muscle component of KATP+ channel-induced relaxation by reducing the levcromakalim-induced decrease in [Ca2+]i via an inhibitory effect on L-type voltage-gated Ca2+ channels.     

The comparative effects of propofol, thiopental, and diazepam, administered intravenously, on pentylenetetrazol seizure threshold in the rabbit.

The anticonvulsant effects of propofol, thiopental, and diazepam, administered intravenously, on pentylenetetrazol (PTZ) seizure threshold were studied and compared in the rabbit. The PTZ seizure threshold determined in various rabbit groups during the control phase of conducted experiments, was found to be in the range of 10.1 +/- 2.0 to 13.5 +/- 3.7 mg/kg. Intravenous administration of comparable doses of propofol, thiopental, and diazepam resulted in marked and significant increases in PTZ seizure threshold. At all administered doses (1.25-10.0 mg/kg), propofol was found to be more effective than thiopental in increasing the PTZ threshold dose. However, the anticonvulsant effects of diazepam were more marked than those of propofol, except at a dose of 10 mg/kg where both agents exhibited equipotent activities. These data demonstrate that propofol enjoys a considerable degree of anticonvulsant activity in the rabbit. This anticonvulsant action is greater than that of thiopental at doses ranging from 2.5 to 10 mg/kg and equipotent with diazepam at the 10 mg/kg dose.     

Effect of thiopental on hippocampal GABA receptors in rat brain

The effect of thiopental on rat brain hippocampal GABA receptors was studied in slice preparations and membrane fractions. In slice preparations, thiopental at a concentration of 10⁻⁵ M enhanced the GABA (1−5 × 10⁻⁴M) inhibition of the field potentials evoked in pyramidal neurons by stratum radiatum stimulation. In hippocampal slices obtained from chronically barbital-administered (100 mg/kg, b.i.d., 10 days) rats, less enhancement of thiopental on GABA inhibition of the field potentials was observed. In binding experiments, two components of specific [³H]GABA binding to membrane fractions were observed. While thiopental was without effect on high-affinity sites, [³H]GABA binding with low affinity was enhanced by 80% in the presence of 10⁻⁵ M thiopental. The results are discussed in relation to the phenomena underlying chronic barbiturate administration.     

猪全胰十二指肠移植术的麻醉技术及围术期管理探讨

目的-以肠内引流(enteric drainage,ED)和门静脉回流(Portal venous drainage,PVD)术式,建立猪全胰十二指肠移植模型,探讨该术式的麻醉及围术期管理方法,为临床胰腺移植积累经验。方法-供、受体猪各20只,基础麻醉后建立心电监护,硫喷妥钠静脉诱导,暴露声门后,静注司可林气管插管,机控呼吸,术中以芬太尼、咪唑安定、哌库溴铵、硫喷妥钠维持麻醉。直视下右颈总动脉、右颈外静脉穿刺置管,连续监测并记录平均动脉压、心率、经皮脉搏氧饱和度及中心静脉压,测定血糖及胰岛素、胰高血糖素水平。结果-成功建立胰腺移植模型并改进了诱导插管方法,气管插管一次成功率95％。采用静脉复合麻醉,苏醒迅速、安全。无胰期积极扩容可保证新胰灌注后呼吸循环稳定。