[Intravenous anesthetics, acting on the gamma-amino butric acid (GABA)A receptor, potentiate the herbal medicine "saiko-keishi-to"-induced chloride current].

We have reported that the Japanese herbal medicine "Saiko-Keishi-To" (SK) which is often used for treating epileptic patients activates the GABAA receptor-mediated chloride current (Icl). In the present study, we examined whether the SK-induced Icl could be potentiated by several intravenous anesthetics known to interact with the GABAA receptor, and also examined whether SK could potentiate the GABA-induced Icl. Whole-cell patch-clamp recordings were made from cultured rat dorsal root ganglion cells. The peak amplitude of the Icl evoked by SK (2 mg.ml-1) increased after pentobarbital (50 microM) to 184 +/- 26% (n = 5), diazepam (1 microM) to 166 +/- 29% (n = 5), and propofol (5 microM) to 294 +/- 93% (n = 5) from their respective controls, while the anesthetics did not activate the Icl by themselves. The peak amplitude of the Icl evoked by GABA (10 microM) increased after propofol (5 microM) to 617 +/- 189% of the control (n = 4), but decreased to 84 +/- 7% of the control by SK (0.2 mg.ml-1, n = 4). These results indicate that the SK-induced Icl can be potentiated by the intravenous anesthetics, positive allosteric modulators of the GABAA receptor-Cl- channel complex and that SK is not a positive allosteric modulator, but a partial agonist for the GABAA receptor. Our study thus suggests that the combined use of SK and anticonvulsants such as barbiturates and benzodiazepines may be more effective in treating epileptic patients than SK alone.

The Japanese herbal medicine 'saiko-keishi-to' activates GABAA receptors of rat sensory neurons in culture.

The mechanism underlying the anticonvulsant action of 'Saiko-Keishi-To' (SK), the Japanese herbal medicine, was examined using whole-cell patch-clamp recording from cultured rat dorsal root ganglion cells. Neurons were held at -60 mV and perfused with an internal solution containing a high concentration of Cl-. Under these circumstances, SK produced an inward current which reversed at +8 mV, and was identical to the gamma-aminobutyric acid (GABA)-induced chloride current (IC). The SK-induced current was completely blocked by bicuculline. SK depressed a high voltage-activated calcium current (HVA-ICa), but this depression could not be antagonized by either phaclofen or saclofen. Of nine crude herbal drugs constituting SK, only Bupleuri radix, Ginseng radix, Zingiberis rhizoma and Paeoniae radix produced the inward currents blocked by bicuculline. These results suggest that SK, and four of its crude herbal drugs, activate the ICl mediated by the GABAA receptor. In addition, SK depresses a HVA-ICa through some mechanism other than an activation of GABAB receptors.

Effect of conventional mechanical ventilation and jet ventilation on airway pressure in dogs and plastic models with tracheal stenosis.

OBJECTIVE: To evaluate the effect of jet ventilation on tracheal stenosis in dogs and plastic models. DESIGN: Prospective, randomized trial in dogs, and multitrial tests in tracheal stenosis models. SETTING: Animal laboratory in a university setting. INTERVENTIONS: Tracheal stenosis was surgically created around the middle of the trachea. Conventional mechanical ventilation and jet ventilation were compared at the same value of Paco2 in dogs and at the same tidal volume in tracheal stenosis models. SUBJECTS: Twelve mongrel dogs and four types of plastic models with combinations of short or long stenosis and fluid or nonfluid stenosis. MEASUREMENTS AND MAIN RESULTS: Canine Studies. Mean peak peak airway pressure values at the distal and proximal portion of the stenosis, and the end-expiratory pressure at the distal portion of the stenosis, were significantly higher during conventional mechanical ventilation than during jet ventilation. The mean values of arterial pressure, pulmonary arterial pressure, central venous pressure, and cardiac output did not change significantly between conventional mechanical ventilation and jet ventilation, except for the pulmonary artery occlusion pressure valve. Plastic Mold Studies. peak airway pressure and end-expiratory airway pressure at the poststenotic trachea during jet ventilation with the model lung were significantly lower than during conventional mechanical ventilation. The difference in peak airway pressure, and end-expiratory airway pressure values between jet ventilation and conventional mechanical ventilation increased more in short stenosis and nonfluid stenosis. CONCLUSIONS: The jet flow that struck the portion of the stenosed wall reversed direction, even during early expiration. Therefore, the expiration during jet ventilation was facilitated more by the reversed flow than by the expiration during conventional mechanical ventilation. This reversed flow may provide lower end-expiratory airway pressure at the poststenotic portion with jet ventilation than with conventional mechanical ventilation. We conclude that jet ventilation was a useful method of ventilation in cases with tracheal stenosis, especially nonfluid and short stenosis.

[The effects of sevoflurane on the coronary circulation in the instrumented dog with or without coronary stenosis].

The effects of sevoflurane on the coronary circulation were investigated in the instrumented dogs with or without coronary stenosis. A-V block was produced by injection of formalin into A-V node to control heart rate at 120 beats.min-1 by pacing and mean systemic blood pressure was held constant at 65 mmHg with the pressurized blood reservoir. Left anterior descending coronary artery was cannulated with stainless steel tube supplied from the femoral artery. Total coronary flow was measured with an electromagnetic flow probe and the regional myocardial blood flow was calculated using color microsphere technique. Coronary resistance was reduced with the increasing end-tidal concentrations of sevoflurane up to 1.2 MAC. An adjustable screw clamp was used to reduce the coronary flow down to 50% of control value. Inner/outer ratio of regional myocardial blood flow decreased with stenosis, but was unaffected with 1.2 MAC of sevoflurane. We concluded that 1.2 MAC of sevoflurane was not strong enough to dilate the coronary artery to produce the transmural steal phenomenon in the dog with coronary stenosis. Further investigations are needed to clarify how hemodynamic factors influence the transmural steal phenomenon in myocardium.

Clinical assessment of oxygen delivery and consumption during hypotensive anaesthesia--a clinical application of The Deep Picture.

Usual evaluation of the relationship between oxygen delivery (DO2) and oxygen uptake (VO2) is based on the arterial oxygen tension (pO2), oxygen saturation (sO2), haemoglobin concentration (ctHb), the same indicators in mixed venous blood and cardiac output, sometimes supplemented by the expiratory carbon dioxide concentration. And, so far, the relationship among DO2, VO2 and the new parameters for an evaluation of oxygen status (oxygen extraction tension: px, concentration of extractable oxygen: cx, oxygen compensation factor: Qx) (1) has not been discussed enough. Therefore, this study was designed to evaluate whether the new parameters give the clinically significant information to analyse the relationship between DO2 and VO2 during the acute haemodynamic change with intentionally induced hypotension in anaesthetized adult patients.

Double burst stimulation with submaximal current.

The present study evaluated responses to double burst stimulation (DBS) at supramaximal and submaximal currents in 30 adult patients. Usually, DBS is applied with supramaximal stimulation, but this may be quite uncomfortable for the awake patient. Therefore, the authors investigated whether it is possible to obtain an accurate assessment of significant residual neuromuscular blockade if the stimulus current is reduced to 30 mA. In all patients, neuromuscular response to DBS three three (DBS3.3), DBS three two (DBS3.2) and train-of-four (TOF) stimulation at supramaximal and/or submaximal currents was recorded using a mechanomyograph, and the ratios of the fourth to the first twitch (T4/T1) induced by TOF stimulation at supramaximal current, and the height of the second response to the first (D2/D1) induced by DBS at 30 mA and supramaximal current were calculated. The relations between control T4/T1 ratios determined by supramaximal TOF stimulation and D2/D1 ratios determined by supramaximal DBS3.3 and submaximal DBS3.3 were Y = 0.99X + 0.08 and Y = 1.01X + 0.04, respectively, and there was no statistical difference between the two regression lines. The same relation between T4/T1 ratios and D2/D1 ratios by DBS3.2 were Y = 0.69X + 0.05 and Y = 0.72X + 0.02, respectively, and there was no significant difference. It is concluded that evaluation of the response to DBS at 30 mA has the same reliability as evaluation with supramaximal current.

Local anesthetics depress the calcium current of rat sensory neurons in culture.

BACKGROUND: Local anesthetics are known to inhibit the voltage-gated sodium current (INa) of the nerve membrane, but it has not been fully studied whether anesthetic concentrations of local anesthetics depress the voltage-gated calcium current (ICa) of mammalian neurons. The effects of local anesthetics on ICa evoked in cultured rat dorsal root ganglion cells were studied. METHODS: Whole cell patch clamp recordings were made from rat dorsal root ganglion cells cultured for 1-3 weeks. ICa was recorded using patch electrodes filled with Cs-aspartate in Na(+)-free external solution containing 5 mM-Ba2+. All drugs, including local anesthetics, were applied by miniperfusion from micropipettes by pressure ejection. RESULTS: Tetracaine (300 microM) depressed the peak amplitudes of high voltage-activated (HVA)-ICa to 22.6 +/- 8.8% of control values (n = 14) without affecting the current-voltage relation. A tetracaine dose-response curve for HVA-ICa indicated an apparent dissociation constant of 79.5 microM. Tetracaine (30 microM) depressed nicardipine-sensitive HVA-I(Ca) (L-type) to 14.3 +/- 6.7% (n = 6), omega-conotoxin-sensitive HVA-ICa (N-type) to 81.6 +/- 9.6% (n = 7), and low voltage-activated (LVA)-ICa (T-type) to 65.1 +/- 11.1% (n = 6) of their respective controls. Local anesthetics other than tetracaine also depressed HVA-ICa but were of different potency; the rank sequence was dibucaine > tetracaine > bupivacaine >> procaine = lidocaine. CONCLUSIONS: These results suggest that both HVA-ICa and LVA-ICa are depressed by tetracaine used at the concentrations required for spinal anesthesia and that the L-type Ca2+ channel among Ca2+ channel subtypes is the most susceptible to tetracaine. A good correlation between local anesthetic potencies to inhibit HVA-ICa and their anesthetic potencies implies that the inhibition of calcium influx through voltage-gated channels may contribute to spinal anesthetic mechanisms.

[A new neuromuscular transmission monitor (TOF Guard): the rationale behind the method and its clinical usefulness].

TOF Guard is one of the latest developments in the field of neuromuscular monitoring equipment. This system uses a miniature acceleration transducer (a piezo-electric ceramic wafer is used), simply fastened to the thumb with tape. The rationale behind the method is Newton's second law, stating that the acceleration is directly proportional to the force. In this study, authors assessed the accuracy of this system in clinical use, comparing with the force transducer method (Myograph 2000). The result showed that there was a very close positive correlation between the values of T1, TOF ratio and posttetanic count simultaneously measured by both methods. The coefficient of correlation was 0.96, and its significance level was P < 0.001. From the clinical view point, it is concluded that TOF Guard is very useful because of its accuracy and because the equipment is easy to handle, compact and of low price as a neuromuscular monitoring system for routine anesthesia.

Neuromuscular and hemodynamic effects of mivacurium and succinylcholine in adult patients during nitrous oxide-propofol-fentanyl anesthesia.

The neuromuscular and hem+odynamic effects of mivacurium 0.15 mg/kg and succinylcholine 1 mg/kg were compared in 26 adult patients (ASA I and II) during nitrous oxide-oxygen-propofol-fentanyl anesthesia. Neuromuscular block was monitored by recording the compound electromyogram of the hypothenar muscle resulting from supramaximal train-of-four stimuli applied to the ulnar nerve. Time to onset of over 95% block and duration to 25% recovery of control twitch after injection of mivacurium were significantly longer than for succinylcholine (201 +/- 37.6 vs 54 +/- 5.2 sec and 13.0 +/- 2.2 vs 8.4 +/- 2.1 min; mean +/- SD). Onset of mivacurium with priming technique was shortened (125 +/- 20.7 sec), but was also slower than that of succinylcholine. Although the recovery index during spontaneous recovery was significantly longer for mivacurium than for succinylcholine (6.9 +/- 1.3 vs 5.1 +/- 0.9 min), antagonism with neostigmine at 25% recovery of twitch height sufficiently facilitated the recovery index of mivacurium (4.5 +/- 1.0 min) to a level similar to that of succinylcholine with no statistical difference. The hemodynamic effects of mivacurium were few as compared to those of succinylcholine. In conclusion, mivacurium is considered to have additional advantages for short procedures when succinylcholine is undesirable.

Dose-response relation and time course of action of pipecuronium in patients anesthetized with nitrous oxide and sevoflurane.

The dose-response relation of pipecuronium, the time course of its neuromuscular blocking effects, and the reversibility of the residual block by neostigmine have been investigated in patients under sevoflurane/N2O Anesthesia using a neuromuscular transmission analyzer (Accelograph, Biometer, Denmark). After an initial dose of pipecuronium (0.04 mg.kg(-1), i.v.), the maximum block rate, onset time, the time from administration until 25% recovery and 50% recovery of control twitch height of the first response to train-of-four nerve stimulation and the interval time of administration of maintenance dose (0.005 mg.kg(-1), i.v.) were 93.7 +/- 7.68%, 5.0 +/- 1.84, 55.4 +/- 23.92, 73.0 +/- 29.44 and 38.7 +/- 15.50 minutes, respectively. The average intubation score (excellent; 0, good; 1 fair; 2, poor; 3) was 0.63 +/- 0.56 at the level of 95.88 +/- 5.06% block. Neostigmine (1.5 mg) promptly reversed the residual neuromuscular blockade induced by pipecuronium (reversal time: 10.1 +/- 2.98 minutes). No side effects attributable to pipecuronium was seen in this study. In conclusion, pipecuronium is a very useful nondepolarizing neuromuscular blocking agent especially for moderately long surgical procedure over 4-5 hours.

Intra-operative blood pressure control by prostaglandin E1 in patients with hypertension and ischemic heart disease--a multi-center study.

The purpose of this multi-center study was to evaluate the efficacy and safety of prostaglandin E1 (PGE1) administration in achieving deliberate hypotension and in treating intraoperative hypertension for patients with a history of hypertension and ischemic heart disease. PGE1 (0.08 microg.kg(-1).min(-1)) decreased systolic blood pressure from 125 +/- 29 to 106 +/- 22 mmHg (mean +/- SD) in the deliberate hypotension group (n = 158) and from 155 +/- 34 to 125 +/- 32 mmHg in the antihypertension group (n = 55). The heart rate significantly increased from 80 +/- 15 to 85 +/- 18 beats.min(-1) in the deliberate hypotension group, but was not significantly altered in the antihypertension group. The time required to obtain the desired level of blood pressure was approximately 20 min in the deliberate hypotension group. When the infusion was stopped, blood pressure returned approximately to the preinfusion level within about 20 min. No rebound hypertension was observed. PGE1 significantly increased the urine flow in patients who had a low urine flow before PGE1 infusion. Thirteen out of 213 patients (5.6%) had side effects such as excessive hypotension (1%), phlebitis (3%), and unexpected tachycardia (1%), which were alleviated gradually after discontinuation of PGE1 infusion. No dysarrhythmia and further ST segment changes in the electrocardiograms were observed. These findings suggest that PGE1 can be safely used to control arterial blood pressure during surgery in patients having preoperative hypertension and ischemic heart disease.

[Changes in epidural pressure during epidural injection].

To evaluate the change of epidural pressure when local anesthetic was injected into epidural space, we inserted three epidural catheters in 13 patients. Epidural catheters were inserted at Th8/9, Th10/11 and L3/4 intervertebral spaces, and 2% mepivacaine 10 ml was injected through Th10/11 or L3/4 catheter. The change of epidural pressure was recorded from three catheters. The elevation of pressure was largest in the injected catheter, but the pattern of elevation was similar in all three catheters. The results suggest that the elevation of epidural pressure occurs at the same time all over the epidural space when local anesthetic is injected.

Modulatory effect of acupuncture on the cardiovascular system: a cross-over study.

The effect of acupuncture on the cardiovascular system was studied in 23 healthy males in a cross-over design comparing acupuncture and a placebo pill by measuring skin blood flow and the function of the heart. Acupuncture was found to have a modulatory effect on skin blood flow (correlation coefficient (r) = -0.68; p < 0.0005) and heart rate (r = -0.56; p < 0.005), as well as Blood-Pressure-Heart-Rate-Product (r = -0.70; p < 0.0002). The combination of rest and a placebo pill had no modulatory effect on skin blood flow, but did have a delayed effect on the heart when compared with acupuncture. The results indicate that acupuncture has the ability to enhance the regulatory mechanisms of the cardiovascular system. The possible underlying mechanism is discussed. The findings represent a physiological explanation for the possible utility of acupuncture in maintaining cardiovascular homeostasis in healthy people.

Determining the optimal time for endotracheal intubation during onset of neuromuscular blockade.

The disappearance of the response to single twitch stimulation (STS), double burst stimulation (DBS) and zero post-tetanic count (PTC) were evaluated to determine which best indicated the optimal time of endotracheal intubation during onset of neuromuscular blockade induced by vecuronium (0.08 mg kg-1) in 199 patients under thiopentone and halothane anaesthesia. Evaluations were performed by mechanomyographic and manual methods using a Myograph and a peripheral nerve stimulator. The study consisted of six parts. In part 1 (n = 30) and part 2 (n = 30), the response to STS (0.1 Hz) were evaluated mechanically and manually, respectively. In part 3 (n = 64), post-tetanic count (PTC) changes were evaluated mechanically. In part 4 (n = 30) and part 5 (n = 30), response to DBS were evaluated mechanically and manually, respectively. Intubation was performed immediately after obtaining zero PTC, or absence of response to STS (0.1 Hz) and DBS, and the intubation score was determined. In the control group of patients, intubation was performed under the same anaesthetic conditions as in parts 1-5 but without the administration of any muscle relaxant. The time from administration of any muscle relaxant. The time from administration of vecuronium until disappearance of response was 2.16 +/- 0.56, 2.49 +/- 0.68, 2.04 +/- 0.29, 2.20 +/- 0.53, and 2.97 +/- 0.61 min in parts 1-5, respectively. Excellent intubation conditions were not established in any of the control patients, and in 50.0, 70.0, 55.0, 70.0 and 90.0% of the patients in parts 1-5, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical significance of posttetanic count (PTC) during onset and spontaneous offset of neuromuscular blockade induced by vecuronium].

To compare the clinical difference of posttetanic count (PTC) during onset and spontaneous offset, the changes of PTC during an intense neuromuscular blockade induced by vecuronium (0.08 mg.kg-1, i.v.) were measured using a neuromuscular transmission analyzer in 64 adult patients anesthetized with nitrous oxide and halothane. Furthermore, intubation score was evaluated when zero PTC was obtained. The obvious movement of diaphragm associated with endotracheal intubation was observed in 9 out of 20 patients (45%) even when it was performed after obtaining zero PTC. The difference of PTC responses between the onset and the offset was found. The difference was that, during the onset, a tetanic response was observed obviously and the height of the posttetanic single twitch was low, and during offset, even when no response was observed, the height of a posttetanic single twitch response was high with the same PTC. These facts indicate that the same PTC has different clinical significance during onset and offset.

Halothane-induced hyperpolarization and depression of postsynaptic potentials of guinea pig thalamic neurons in vitro.

Intralaminar thalamic nuclei have been considered to be a component of the non-specific sensory system which is involved in physiological functions related to consciousness and pain sensation. The effect of halothane on membrane potentials and synaptic properties of neurons of the parafascicular (Pf) nucleus in guinea pig brain slices was investigated using intracellular recording methods. Halothane at concentrations of 0.4-1.0 mM, which are in the range of clinical concentrations, produced hyperpolarizations of 2-8 mV in approximately 50% of the cells. The halothane-induced hyperpolarization was nullified at a membrane potential close to the K+ equilibrium potential. The amplitude of the hyperpolarization was dependent on the external K+ concentration, and was decreased by either Ba2+, or 4-aminopyridine, or intracellular injection of Cs+. All these results indicate that the hyperpolarization was due to an increase in K+ conductance. Halothane at clinical concentrations depressed both excitatory and inhibitory postsynaptic potentials in a concentration-dependent manner. On the other hand hyperpolarizing responses to exogenous gamma-aminobutyric acid (GABA) in the presence of bicuculline were suppressed by halothane, but depolarizing responses to L-glutamate were not altered. The results indicate that the depressant action of the anesthetic on the excitatory postsynaptic potential (EPSP) may occur presynaptically, whereas the blocking action on the inhibitory postsynaptic potential (IPSP) may occur postsynaptically.

MRI findings of DREZ-otomy lesions.

Pre- and postoperative MR findings in the spinal cord of 4 patients who underwent lesioning of the cervical dorsal root entry zone (DREZ-otomy) are reported. In 3 patients with root avulsion, MR images revealed spinal cord atrophy preoperatively and, after DREZ-otomy, long-lasting spinal cord enlargement and extensive intramedullary changes. In a case without root avulsion, the preoperative MR study showed no apparent abnormality and the only postoperative MR change was a discrete lesion well confined to the dorsal horn. The findings suggested basically different post-operative pathology among patients with root avulsion and those without. MRI can be a useful supplement to autopsy study in defining postoperative spinal cord changes after DREZ-otomy.

Common factors contributing to intractable pain and medical problems with insufficient drug uptake in areas to be treated, and their pathogenesis and treatment: Part I. Combined use of medication with acupuncture, (+) Qi gong energy-stored material, soft laser or electrical stimulation.

Most frequently encountered causes of intractable pain and intractable medical problems, including headache, post-herpetic neuralgia, tinnitus with hearing difficulty, brachial essential hypertension, cephalic hypertension and hypotension, arrhythmia, stroke, osteo-arthritis, Minamata disease, Alzheimer's disease and neuromuscular problems, such as Amyotrophic Lateral Sclerosis, and cancer are often found to be due to co-existence of 1) viral or bacterial infection, 2) localized microcirculatory disturbances, 3) localized deposits of heavy metals, such as lead or mercury, in affected areas of the body, 4) with or without additional harmful environmental electro-magnetic or electric fields from household electrical devices in close vicinity, which create microcirculatory disturbances and reduced acetylcholine. The main reason why medications known to be effective prove ineffective with intractable medical problems, the authors found, is that even effective medications often cannot reach these affected areas in sufficient therapeutic doses, even though the medications can reach the normal parts of the body and result in side effects when doses are excessive. These conditions are often difficult to treat or may be considered incurable in both Western and Oriental medicine. As solutions to these problems, the authors found some of the following methods can improve circulation and selectively enhance drug uptake: 1) Acupuncture, 2) Low pulse repetition rate electrical stimulation (1-2 pulses/second), 3) (+) Qi Gong energy, 4) Soft lasers using Ga-As diode laser or He-Ne gas laser, 5) Certain electro-magnetic fields or rapidly changing or moving electric or magnetic fields, 6) Heat or moxibustion, 7) Individually selected Calcium Channel Blockers, 8) Individually selected Oriental herb medicines known to reduce or eliminate circulatory disturbances. Each method has advantages and limitations and therefore the individually optimal method has to be selected. Applications of (+) Qi Gong energy stored paper or cloth every 4 hours, along with effective medications, were often found to be effective, as Qigongnized materials can often be used repeatedly, as long as they are not exposed to rapidly changing electric, magnetic or electro-magnetic fields. Application of (+) Qi Gong energy-stored paper or cloth, soft laser or changing electric field for 30-60 seconds on the area above the medulla oblongata, vertebral arteries or endocrine representation area at the tail of pancreas reduced or eliminated microcirculatory disturbances and enhanced drug uptake.(ABSTRACT TRUNCATED AT 400 WORDS)

Is the diagnosis of significant residual neuromuscular blockade improved by using double-burst nerve stimulation?

This study evaluated the use of double-burst stimulation (DBS) in the diagnosis of significant post-operative residual neuromuscular blockade. Ninety patients were allocated to three equal groups. In Group A the degree of residual neuromuscular blockade was assessed by clinical criteria (CC) only; in Group B by CC and manual evaluation of the response to train-of-four (TOF) nerve stimulation; and in Group C by CC, manual evaluation of the response to TOF, and DBS stimulation. Immediately after arrival in the recovery room mechanical twitch was recorded using TOF stimulation. The mean (+/- SD) TOF ratios were 0.53 +/- 0.19 in Group A, 0.67 +/- 0.11 in Group B and 0.81 +/- 0.08 in Group C. The incidence of a TOF ratio of less than 0.7 was 83.3% in Group A, 56.7% in Group B and 6.7% in Group C. It is concluded that the use of DBS enabled the anaesthetist to recognize significant residual block and thus reduced the incidence of post-operative residual neuromuscular blockade.