The effects of halothane or isoflurane, alone and in combination with propofol or thiopental were investigated for their effects on intracranial pressure (ICP) in the rabbit, with inducing artificially-increased ICP with an intracranial balloon. The higher the end-tidal concentrations of either halothane or isoflurane, the lower the mean arterial pressures (MAP) and cerebral perfusion pressures (CPP). However, the ICP was not influenced by the depth of anesthesia for either inhalation anesthetics. The mean ICPs at 1.5 MAC of halothane and isoflurane were 14 +/- 2 and 20 +/- 2 mmHg, respectively. With the increase of intracranial volume using a 0.7 ml-saline balloon, the ICPs were increased to 193 and 205% in halothane and isoflurane anesthesia, respectively. The ICPs were returned to the levels prior to balloon inflation by the injection of thiopental or propofol. The authors conclude that propofol could be used to reduce ICP under halothane or isoflurane anesthesia if it is ascertained to have the characteristics of a balanced coupling between cerebral metabolism and blood flow like barbiturates do and that either halothane or isoflurane with increased concentrations may decrease MAP without significant change of ICP.
*Anesthesia ; Animal ; Female ; *Halothane ; Intracranial Pressure/*drug effects ; *Isoflurane ; Male ; Propofol/*pharmacology ; Rabbits ; Thiopental/*pharmacology

To investigate the effect of thiopental sodium on the release of glutamate and gamma-aminobutyric acid (GABA) from synaptosomes in the prefrontal cortex, synaptosomes were made, the spontaneous release and the evoked release by 30 mmol/L KCl or 20 micromol/L veratridine of glutamate and GABA were performed under various concentrations of thiopental sodium (10-300 micromol/L), glutamate and GABA concentrations were determined by reversed-phase high-performance liquid chromatography. Our results showed that spontaneous release and evoked release of glutamate were significantly inhibited by 30 micromol/L, 100 micromol/L and 300 micromol/L thiopental sodium, IC50 of thiopental sodium was 25.8 +/- 2.3 micromol/L for the spontaneous release, 23.4 +/- 2.4 micromol/L for KCl-evoked release, and 24.3 +/- 1.8 micromol/L for veratridine-evoked release. But GABA spontaneous release and evoked release were unaffected. The study showed that thiopental sodium with clinically related concentrations could inhibit the release of glutamate, but had no effect on the release of GABA from rats prefrontal cortical synaptosomes.
Glutamic Acid/*metabolism ; Hypnotics and Sedatives/pharmacology ; Prefrontal Cortex/*metabolism ; Rats, Sprague-Dawley ; Synaptosomes/*metabolism ; Thiopental/*pharmacology ; gamma-Aminobutyric Acid/*metabolism

Effects of beta-adrenergic blockers and related agents were investigated on experimental convulsions of chicks induced with strychnine, pentylenetetrazol or electroshock and on thiopental sleeping time of rabbits. Convulsions of chicks due to strychnine were significantly inhibited by all beta-adrenergic blockers except dichloroisopreterenol. Propranolol inhibited electroshock convulsion as well, but none of the blockers inhibited pentylenetetrazol convulsion. Furthermore, the mortality of chicks due to large dose of pentylenetetrazol was greatly increased by treatment of beta-adrenergic blockers. Pindolol alone showed diazepam-like anticonvulsive effect against low doses of pentylenetetrazol. Pretreatment with beta-adrenergic blockers caused a marked increase in thiopental sleeping time in rabbits. Prolongation of thiopental sleep due to propranolol was abolished by premedication of animals with reserpine or tranylcypromine. Thiopental sleeping time was prolonged by Zizyphus extract, though less effective than beta-adrenergic blockers. It is felt that the anticonvulsive or sleep enhancing effect of beta-adrenergic blocking agents has an intimate relationship with endogenous adrenergic amines and the receptors.
Adrenergic beta-Antagonists/pharmacology* ; Anesthesia ; Animal ; Anticonvulsants* ; Blood Pressure/drug effects ; Chickens ; Convulsions/chemically induced ; Heart Rate/drug effects ; Male ; Propranolol/pharmacology* ; Rabbits ; Strychnine/antagonists & inhibitors ; Thiopental

To investigate the effect of thiopental sodium on the release of glutamate and gamma-aminobutyric acid (GABA) from synaptosomes in the prefrontal cortex, synaptosomes were made, the spontaneous release and the evoked release by 30 mmol/L KCl or 20 micromol/L veratridine of glutamate and GABA were performed under various concentrations of thiopental sodium (10-300 micromol/L), glutamate and GABA concentrations were determined by reversed-phase high-performance liquid chromatography. Our results showed that spontaneous release and evoked release of glutamate were significantly inhibited by 30 micromol/L, 100 micromol/L and 300 micromol/L thiopental sodium, IC50 of thiopental sodium was 25.8 +/- 2.3 micromol/L for the spontaneous release, 23.4 +/- 2.4 micromol/L for KCl-evoked release, and 24.3 +/- 1.8 micromol/L for veratridine-evoked release. But GABA spontaneous release and evoked release were unaffected. The study showed that thiopental sodium with clinically related concentrations could inhibit the release of glutamate, but had no effect on the release of GABA from rats prefrontal cortical synaptosomes.
Animals ; Glutamic Acid ; metabolism ; Hypnotics and Sedatives ; pharmacology ; Male ; Prefrontal Cortex ; metabolism ; Rats ; Rats, Sprague-Dawley ; Synaptosomes ; metabolism ; Thiopental ; pharmacology ; gamma-Aminobutyric Acid ; metabolism

AIMTo observe the effects of lidocaine and thiopental on the neuronal injury induced by the experimental ischemia in hippocampus slice cultures obtained from postnatal 22 days SD rats.

METHODSModel of the experimental ischemia was produced by hypoxia and glucose deprivation. Propidium iodide (PI) assay was used to observe the neuronal injury in CA1 and dentate gyrus (DG).

RESULTSAfter experimental ischemia, the peak of PI index was appeared in CA1 and DG on the first day (P < 0.01), PI index in DG was less than in CA1 (P < 0.01). PI indices were still higher during seven days after the experimental ischemia than before the experimental ischemia (P < 0.01). 10 nmol/L and 100 nmol/L concentration of lidocaine could significantly decrease PI indices in CA1 and DG (P < 0.01). 250 nmol/L and 600 nmol/L concentration of thiopental also decreased the PI indices in CA1 and DG (P < 0.01). The neuronal injury peaks were postponed to the third day after the experimental ischemia by lidocaine and thiopental.

CONCLUSIONIt suggested that lidocaine and thiopental could decrease the neuronal injury in CA1 and DG induced by the experimental ischemia, and postpone the neuronal injury peaks to the third day after the experimental ischemia.

Animals ; Brain Ischemia ; pathology ; CA1 Region, Hippocampal ; drug effects ; pathology ; In Vitro Techniques ; Lidocaine ; pharmacology ; Neurons ; drug effects ; pathology ; Rats ; Thiopental ; pharmacology

OBJECTIVETo investigate the effects of propofol, midazolam and thiopental sodium on outcomes and amino acid accumulation in focal cerebral ischemia-reperfusion in rats.

METHODSMale Sprague Dawley (SD) rats were scheduled to undergo 3-hour middle cerebral artery occlusion by intraluminal suture and 24-hour reperfusion. Neurologic outcomes were scored on a 0-5 grading scale. Infarct volume was shown with triphenyltetrazolium chloride staining and measured by an image analysis system. Concentrations of various amino acids (aspartate, glutamate, glycine, taurine, and gama-aminobutyric acid) were measured after 3 hours of reperfusion using high performance liquid chromatography. Propofol, midazolam and thiopental sodium were given intraperitoneally at the beginning of reperfusion.

RESULTSBoth propofol and midazolam attenuated neurological deficits and reduced infarct and edema volumes. Propofol showed better neurological protection than midazolam while thiopental sodium did not exhibit any protective effect. Both propofol and midazolam decreased excitatory amino acids accumulation, while propofol increased gama-aminobutyric acid accumulation in ischemic areas in reperfusion.

CONCLUSIONPropofol and midazolam, but not thiopental sodium, may provide protective effects against reperfusion induced injury in rats subjected to focal cerebral ischemia. This neurological protection may be due to the acceleration of excitatory amino acids elimination in reperfusion.

Adenosine Triphosphate ; metabolism ; Animals ; Brain ; metabolism ; Brain Edema ; drug therapy ; Brain Ischemia ; metabolism ; Excitatory Amino Acids ; metabolism ; Male ; Midazolam ; pharmacology ; Myocardial Infarction ; drug therapy ; Neuroprotective Agents ; pharmacology ; Propofol ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control ; Thiopental ; pharmacology

Among nondepolarizing neuromuscular blocking agents, d-tubocurarine may cause blood pressure reduction due to ganglionic blockade and histamine release, while pancuronium and gallamine are associated with vagal blockade and heart rate acceleration. Metocurine, as a trimethylated derivative of d-tubocurarine synthesized by King in 1935, is known to have relatively long duration of action and produces little change in cardiovascular system. Despite its relative lack of cardiovascular effects, the accumulation of data with regard to human neuromus- cular pharmacology and the clinical use has been scant. One hundred and nine adult patients of either sex were anesthetized with thiopental sodium and 50% nitrous oxide with 1.5-2.5% enflurane. For evaluation of neuromuscular blocking effect of metocurine, train-of-four stimulation (2.0 Hz for 2 seconds) was applied at the wrist along the ulnar nerve distribution and the response was measured via ABM Datex. Systolic, diastolic blood pressure and heart rate were recorded continuously after administration of metocurine, d-tubocurarine or pancuronium. All data were analized by ANOVA, Scheffe test. The results are follows : 1) The mean onset times of metocurine 0.1, 0.2, 0.3 mg/kg groups were 119.5+/-40.0, 120.9+/-61.1, 84.8+/-61,1 seconds and the mean durations were 75.1+/-37.6, 104.9+/-42.1, 131.0+/-42.5 minutes respectively. 2) Single-bolus dose of metocurine 0.1, 0.2, and 0.3 mg/kg did not cause significant cardiovascular changes from the control values, but d-tubocurarine 0.3 mg/kg decreased mean systolic blood pressure significantly from 116.6+/-15.7 to 99.0+/-10.9 mmHg 2 minutes after injection. 3) Systolic blood pressures of metocurine 0.2 mg/kg (107.2+/-11.7 mmHg) and d-tubocurarine 0.3 mg/ kg (100.4+/-12.9 mmHg) were significantly different from that of pancuronivm 0.06 mg/kg (127.8+/-16. 0 mmHg) after 1 minute, and 2 minutes after injection, systolic blood pressure of metocurine 0.2 mg/ kg (110.2+/-14.3 mmHg) and d-tubocurarine 0.3 mg/kg (99.0+/-10.9 mmHg) were different from that of pancuronium 0.06 mg/kg (125.3+13.1 mmHg). Five minutes after injection, systolic pressure of d- tubocurarine 0.3mg/kg group (101.110.2mmHg) was significantly different from that of pancur-onium 0.06 mg/kg group (118.7+/-11.0 mmHg). 4) Diastolic blood pressure of d-tubocurarine 0.3 mg/kg (63.4+/-12.9 mmHg) was significantly differ- ent from that of pancuronium 0.06mg/kg (84.2+/-13.3mmHg) after 1 minute, and 2 minutes after injection, diastolic blood pressure or d-tubocurarine 0.3 mg/kg (65.4+/-11.3 mmHg) was different from that of pancuronium 0.06mg/kg (83.1+/-11.6mmHg). There was no significant difference among the groups with respect to heart rate. In summary, metocurine has relatively rapid onset and long duration of action, and used in a dose sufficient to provide surgical relaxation, it produces little change in cardiovascular system in contrast to d-tubocurarine or pancuronium. 1t is therefore suggested that metocurine may be recommended as a muscle relaxant for patients having cardiovascular disease.
Acceleration ; Adult ; Blood Pressure ; Cardiovascular Diseases ; Cardiovascular System ; Enflurane ; Gallamine Triethiodide ; Ganglion Cysts ; Heart Rate ; Hemodynamics* ; Histamine Release ; Humans ; Neuromuscular Blockade* ; Neuromuscular Blocking Agents ; Nitrous Oxide ; Pancuronium ; Pharmacology ; Relaxation ; Thiopental ; Tubocurarine ; Ulnar Nerve ; Wrist

PURPOSE: Ca2+ homeostasis plays an important role in myocardial cell injury induced by hypoxia-reoxygenation, and prevention of intracellular Ca2+ overload is key to cardioprotection. Even though thiopental is a frequently used anesthetic agent, little is known about its cardioprotective effects, particulary in association with Ca2+ homeostasis. We investigated whether thiopental protects cardiomyocytes against hypoxia-reoxygenation injury by regulating Ca2+ homeostasis. MATERIALS AND METHODS: Neonatal rat cardiomyocytes were isolated. Cardiomyocytes were exposed to different concentrations of thiopental and immediately replaced in the hypoxic chamber to maintain hypoxia. After 1 hour of exposure, a culture dish was transferred to the CO2 incubator and cells were incubated at 37degrees C for 5 hours. At the end of the experiments, the authors assessed cell protection using immunoblot analysis and caspase activity. The mRNA of genes involved in Ca2+ homeostasis, mitochondrial membrane potential, and cellular Ca2+ levels were examined. RESULTS: In thiopental-treated cardiomyocytes, there was a decrease in expression of the proapoptotic protein Bax, caspase-3 activation, and intracellular Ca2+ content. In addition, both enhancement of anti-apoptotic protein Bcl-2 and activation of Erk concerned with survival were shown. Furthermore, thiopental attenuated alterations of genes involving Ca2+ regulation and significantly modulated abnormal changes of NCX and SERCA2a genes in hypoxia-reoxygenated neonatal cardiomyocytes. Thiopental suppressed disruption of mitochondrial membrane potential (Delta Psi m) induced by hypoxia-reoxygenation. CONCLUSION: Thiopental is likely to modulate expression of genes that regulate Ca2+ homeostasis, which reduces apoptotic cell death and results in cardioprotection.
Animals ; Apoptosis ; Calcium/*metabolism ; Cell Hypoxia/*physiology ; Cell Survival/drug effects ; Cells, Cultured ; GABA Modulators/*pharmacology ; Homeostasis/drug effects ; Immunoblotting ; In Situ Nick-End Labeling ; Membrane Potential, Mitochondrial/drug effects ; Microscopy, Confocal ; Myocytes, Cardiac/*drug effects/*metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Thiopental/*pharmacology

The purpose of this study was to determine the effectiveness of antihistamine therapy for withdrawal movements caused by rocuronium injection. One hundred seventy one ASA I-II adults undergoing elective surgery were randomly assigned to one of two groups. Patients in the control group (Group C) were premedicated with 2 mL normal saline, and those in the antihistamine group (Group A) were pre-medicated with 2 mL (45.5 mg) pheniramine maleate. After the administration of thiopental sodium 5 mg/kg, rocuronium 0.6 mg/kg was injected. Withdrawal movements were assessed using a four-grade scale. The administration of antihistamine reveals lower grade of withdrawal movement after rocuronium injection.
Adult ; Androstanols/*administration & dosage/adverse effects ; Anesthetics, Intravenous/administration & dosage ; Double-Blind Method ; Female ; Histamine H1 Antagonists/*pharmacology ; Humans ; Incidence ; Injections, Intravenous ; Male ; Middle Aged ; Movement/drug effects/physiology ; Neuromuscular Nondepolarizing Agents/*administration & dosage/adverse effects ; Pain/chemically induced ; Pain Measurement ; Pheniramine/*pharmacology ; Thiopental/administration & dosage