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BACKGROUND Acetylcholine (ACh) is one of the major excitatory neurotransmitters in the central nervous system, and changes in neural activity induced by anesthesia alter the release of ACh. However, the effects of isoflurane, one of the most widely used volatile anesthetics, on ACh release are not known. The present study attempts to clarify the dose-effect relationship of isoflurane on the in vivo release of ACh in rat brains. METHODS Changes in the extracellular concentration of ACh and choline in the cerebral cortex and striatum induced by 0.5, 1.0, and 1.5 minimum alveolar concentration (MAC) of isoflurane were determined using a brain microdialysis technique. RESULTS In the cortex, the ACh release decreased to 30.8+/-10.1 (mean+/-SEM), 10.2+/-4.1, and 8.1+/-2.9% of basal value by increasing doses of isoflurane, and in the striatum, to 73.3+/-4.4, 49.2+/-4.2, and 40.7+/-4.5%. The ACh release rapidly recovered control levels with the discontinuance of isoflurane. Choline concentration was not changed significantly by isoflurane except for a decrease to 74.8+/-4.6% in the striatum by 0.5 MAC. In both the cortex and striatum, the choline concentration decreased with the discontinuance of isoflurane to 70.3+/-13.3, and 68.2+/-5.4%, respectively. CONCLUSION The fact that all classic anesthetics reported previously, as well as isoflurane, reduce ACh release supports the hypothesis that the suppression of cholinergic cells is, at least in part one of the mechanisms of anesthesia.

To investigate the clinical significance of endothelin (ET), a potent vasoconstrictor peptide, in subarachnoid hemorrhage (SAH) and SAH-related cerebral vasospasm, we measured the ET-like immunoreactivity (ET-LI) in plasma and cerebrospinal fluid (CSF) obtained serially from patients with SAH due to ruptured cerebral aneurysm who underwent aneurysmal surgery. The normal ET-LI levels in plasma and CSF (n = 24) were 12.4 +/- 2.0 (mean +/- s.d.) and 9.1 +/- 1.2 pg.ml-1, respectively. Plasma ET-LI levels in patients with SAH before surgery (16.8 +/- 7.8 pg.ml-1, n = 8) were higher than the normal values (P < 0.05), and became further elevated after surgery (22.5 +/- 9.4 pg.ml-1). ET-LI levels in plasma and CSF one day after surgery were 18.7 +/- 5.5 and 18.4 +/- 6.8 pg.ml-1 (P < 0.01 vs. normal values), respectively, and declined thereafter. The plasma and CSF ET-LI levels in patients who showed symptomatic vasospasm became concomitantly elevated again. These results suggest that ET is involved in SAH-related vasospasm and raise the possibility that surgical stress influences the vasospasm.

The in vitro effects of halothane on the potassium-stimulation-induced efflux of [3H]D-aspartate in rat cerebral cortex slices were studied. The slices were initially incubated with Krebs-Ringer's solution containing [3H]D-aspartate, a putative excitatory transmitter. The slices were then stimulated with high concentrations of K+ in the presence and absence of halothane, and the efflux was measured using a scintillation counter. Halothane, 1% and 2%, had little effect on the potassium-stimulation-induced efflux, but that of 4 and 8% increased the efflux significantly. The spontaneous efflux was unaffected by all concentrations of halothane studied. The control study of pentobarbital, in the concentration of 0.05 to 1.00 mmol/l, reduced the efflux in a dose-related manner. These findings indicate that the release of an excitatory transmitter, aspartate, may not be involved in the mechanism of halothane anaesthesia.

The effects of halothane on diazepam binding to the rat cerebral synaptic membranes were investigated. Halothane at the concentrations of 0.63, 1.3 and 4.1 mmol/l increased the binding by 12, 23 and 33%, respectively, compared to the control in the absence of halothane. The increments were dependent on the presence of Cl-. The findings indicate that halothane and diazepam have an interaction at receptor level.

In helical strips of dog cerebral and mesenteric arteries previously contracted with KCl or prostaglandin F2 alpha (PGF2 alpha), the addition of pentobarbital (10(-5) to 10(-3) mol.l-1) caused dose-related relaxation, whereas thiamylal and thiopental in a low concentration (10(-5) to 10(-4) mol.l-1) caused further contraction and in a high concentration (10(-3) mol.l-1) profound relaxation. Thiobarbiturate-induced contractions were greater in mesenteric than in cerebral arteries previously contracted with PGF2 alpha. In cerebral and mesenteric arteries exposed to Ca(++)-free media for 60 min and treated with KCl or PGF2 alpha, reintroduction of Ca++ produced a transient contraction, a transient relaxation and a persistent contraction. The Ca(++)-induced persistent contraction was attenuated by pretreatment with pentobarbital (10(-4) to 10(-3) mol.l-1) and thiamylal (10(-3) mol.l-1); the attenuation was greater in arteries treated with KCl than with PGF2 alpha. The Ca(++)-induced contractions of mesenteric artery treated with PGF2 alpha were potentiated by 10(-4) mol.l-1 thiamylal. It is concluded that pentobarbital possesses only a vasodilator effect, whereas thiamylal and thiopental have both constrictor and dilator effects on vascular smooth muscle. The vasodilator effect of barbiturates is associated in part with inhibition of transmembrane influx of Ca++; the inhibition is more predominant on the influx evoked by KCl-induced depolarization than by a stimulation of PGF2 alpha receptors. Thiamylal in low concentrations appears to enhance Ca++ influx through a receptor-operated Ca++ channel for PGF2 alpha.

The effects th groups the changes in CO and SV were due mainly to a reduced demand of oxygen transport and expected changes in sympatho-adrenergic tone rather than to myocardial depression.

Effects of N2O-exposure on the survival rate and growth kinetics of hemopoietic stem cells after irradiation were investigated. LD 50, 30 days after irradiation, was 300 rad for N2O exposed mice and over 550 rad for control mice. Recovery of the pluripotent hemopoietic stem cells (CFU-S) and granulocyte-macrophage progenitor cells (GM-CFC) was significantly delayed in the spleen of N2O-exposed mice after 150 rad irradiation, compared to that of control mice. However, in bone marrow, there was a significant but slight difference in the recovery of GM-CFC and no significant difference in the recovery of CFU-S between the two groups. These results suggest that N2O augments the damage of splenic hemopoiesis in irradiated mice, and this may be responsible for the increased hemopoietic death.

In order to evaluate the effect of isosorbide dinitrate (ISDN), administered as a bolus intravenous injection, on the circulatory response to tracheal intubation, mean arterial pressure (MAP), and heart rate (HR) in response to laryngoscopy for 30 s followed by tracheal intubation were compared in patients not receiving ISDN (control) and receiving 40 micrograms/kg or 80 micrograms/kg of ISDN 45 s before starting laryngoscopy. Each group consisted of 10 patients undergoing elective surgery. Forty-five seconds after starting laryngoscopy, MAP was significantly (P less than 0.01) lower in patients receiving 80 micrograms/kg ISDN than in those receiving no or 40 micrograms/kg ISDN. HR increased to a similar extent in the three groups. These results indicate that a bolus injection of ISDN (80 micrograms/kg) is a simple, practical and highly effective means of attenuating the hypertensive response to direct laryngoscopy and tracheal intubation.

Cats were used to assess the significance of differences in animal preparations in the study of anesthetic-induced analgesia. Comparison was made between pentobarbital-anesthetized and decerebrate non-anesthetized cats. Bradykinin dissolved in normal saline was injected into the femoral artery as a noxious stimulus, and the neural response in the spinal cord lateral funiculus was recorded using the multi-unit activity technique. The magnitude of the neural response and the changes in spontaneous firing were compared before and after cervical cord transection at C1. Before the transection, the response was greater in anesthetized than in decerebrate cats. The cord transection potentiated the response in both preparations, but the degree of potentiation was greater in decerebrate than in anesthetized cats. These studies confirmed the presence of a descending pain inhibition system acting tonically on the nociceptive neural mechanisms in the spinal cord, and indicated the susceptibility of this system to pentobarbital. We conclude that pretreatment with pentobarbital induces pharmacologically a state of partial spinal cord transection and reduces the effects of drugs acting through supraspinal CNS structures.

The effects of several anaesthetics on spinal cord nociceptive neural mechanisms and their interactions with the opiate antagonist, naloxone, were studied in acute, spinal cord transected cats. Intra-arterial injection of bradykinin was used as the noxious test stimulus. Spontaneous activity and the neural response induced by bradykinin were recorded by the multi-unit activity technique in the lateral funiculus of the spinal cord. Naloxone, 0.1 or 2.0 mg/kg i.v. had little effect on the bradykinin-induced response, but enhanced the spontaneous firing of the lateral funiculus significantly. Fentanyl, 30 micrograms/kg i.v., depressed both the bradykinin-induced response and spontaneous firing. These effects of fentanyl were antagonized completely by naloxone, 0.1 mg/kg i.v. Nitrous oxide, thiamylal, halothane and ether depressed the bradykinin-induced response considerably, but it was not antagonized by naloxone, 0.1-2.0 mg/kg i.v. Enflurane had little effect on the bradykinin-induced response. The effects of these anesthetics on spontaneous firing were divergent: nitrous oxide enhanced it while other drugs depressed it, to various degrees. All these data suggest that the neural and/or neurochemical mechanisms of anesthetic-induced analgesia differ from mechanisms related to opioids.

The present study was undertaken to determine the site of action of trimethaphan in causing neuromuscular blockade using isolated rat and frog muscle. Trimethaphan and d-tubocurarine attenuated the twitch tension developed by nerve stimulation, trimethaphan being 1/100 to 1/200 as potent as d-tubocurarine. Neostigmine potentiated the inhibitory effect of trimethaphan but reversed the effect of d-tubocurarine. Trimethaphan shifted the dose response curve of frog rectus abdominis muscle for carbachol downwards, while d-tubocurarine shifted the curve parallel to the right. Treatment with d-tubocurarine or succinylcholine protected acetylcholine receptors from persistent blockade by alpha-bungarotoxin while, in contrast, trimethaphan failed to protect the receptors. The findings indicate that trimethaphan acts on the motor endplate but, unlike d-tubocurarine, does not interact with the recognition site of acetylcholine receptors; the action of trimethaphan appears to be associated with the blockade of endplate ionic channels.

The effects of thiamylal on the nociceptor-driven neural activity in the spinal cord were studied in decerebrate, non-anesthetized cats. Noxious stimulation was induced by the injection of bradykinin into the femoral artery and the neutral response in the lateral funiculus was measured by the multi-unit activity technique. The effects of thiamylal on the bradykinin-induced response were compared before and after the spinal cord transection, above the recording site. Thiamylal, 5 mg/kg i.v., potentiated the response significantly before the cord transection and depressed it after the transection. These findings indicate that the antianalgesic action of thiamylal is induced at the spinal cord level: although this anesthetic agent does have a direct intraspinal depressant action, the multisynaptic neural network of the supraspinal pain inhibition system is more susceptible to the actions of anesthetics, and the depression of this descending system by thiamylal results in a release of spinal cord nociceptive neural mechanisms from the supraspinal control.