Biomedical subjects

Takashi Mashimo

Publications and source records attributed to Takashi Mashimo.

At least 37 records · Page 2Linked to original sources

PubMed2005

Identification of the central imidazoline receptor subtype involved in modulation of halothane-epinephrine arrhythmias in rats.

We previously reported that imidazoline receptors in the central nervous system are involved in modulation of halothane-epinephrine arrhythmias. These receptors have been subclassified as I1 and I2 subtypes, but it is not known which receptor subtype is involved in halothane-epinephrine-induced arrhythmias. We designed the present study to clarify the involvement of central imidazoline receptor subtype in the modulation of halothane-epinephrine-induced arrhythmias. Rats were anesthetized with halothane and monitored continuously for systemic arterial blood pressure and premature ventricular contractions. The arrhythmogenic dose of epinephrine was defined as the smallest dose that produces three or more premature ventricular contractions within a 15-s period. Intracisternal moxonidine dose-dependently inhibited the epinephrine-induced arrhythmias during halothane anesthesia. Intracisternal efaroxan, a selective I1 antagonist with little affinity for I2 subtype, but not rauwolscine, an alpha2 antagonist without affinity for imidazoline receptors, blocked the antiarrhythmic effect of moxonidine. Intracisternal BU 224 and 2-BFI, selective I2 ligands, also inhibited the epinephrine-induced arrhythmias dose-dependently; however, these effects were abolished by efaroxan. We conclude that central I1, but not I2, receptors play an important role in inhibition of halothane-epinephrine arrhythmia.

Animals↗

PubMed2005

Risk stratification for lung cancer surgery: impact of induction therapy and extended resection.

STUDY OBJECTIVES: Current surgical strategies for lung cancer are directed toward the following two distinct targets: the increased prevalence of early-stage lung cancer; and locally advanced lung cancer treated with induction therapy (IT). To establish the risk stratification for operative morbidity from this viewpoint, we evaluated the impact of IT and/or an extended surgical procedure on operative results. DESIGN: Retrospective study. SETTING: A 674-bed teaching hospital. PATIENTS AND METHODS: The morbidity and mortality of 758 consecutive patients who underwent surgery for the treatment of non-small cell lung cancer were analyzed. There were 666 patients who underwent surgery alone (S group; 560 standard lobectomies and 106 extended resections) and 92 patients who received IT (IT group; 35 standard lobectomies and 57 extended resections). Comparisons between the groups were performed using unpaired t tests or chi(2) tests. Univariate and multivariate logistic regression analyses were used to determine the risk factors for operative morbidity and mortality. RESULTS: IT and extended surgery were strong independent factors for predicting postoperative morbidity (p < 0.0001). Significant differences were observed for pathologic stage (p < 0.0001), preoperative hemoglobin and Dlco levels (p < 0.001), the ratio of extended resection (p < 0.0001), and operation time and intraoperative bleeding (p < 0.001) between the S and IT groups. The overall morbidity and mortality rates were 16.8% and 0.9%, respectively, in the S group, and 55.4% and 5.4%, respectively, in the IT group (p < 0.01). The overall morbidity and mortality rates were 63.2% and 7.0%, respectively, for extended resection after IT, and 12.8% and 0.3%, respectively, for those who underwent a standard resection without IT. CONCLUSIONS: The morbidity and mortality of lung resection are both significantly increased after IT, and the patients with the greatest risk are those who have undergone IT and extended resection. The impact of IT on risk stratification should be emphasized in perioperative care.

Adenocarcinoma↗

PubMed2005

Effects of gas leak on triggering function, humidification, and inspiratory oxygen fraction during noninvasive positive airway pressure ventilation.

OBJECTIVES: During noninvasive positive pressure ventilation (NPPV), the gas leak that commonly occurs around the mask can render NPPV ineffective. We evaluated the effects of gas leak on inspiratory trigger function during NPPV with bilevel pressure and ICU ventilators. In addition, we evaluated the effects of gas leak on fraction of inspired oxygen (Fio(2)) and humidification. METHODS: Air leak was created at the airway opening of a model lung by establishing several different-size holes in the circuit. During simulated spontaneous breathing, we evaluated inspiratory trigger performance of two bilevel pressure ventilators (BiPAP Vision and BiPAP S/T-D; Respironics; Murrysville, PA) and two ICU ventilators (Puritan-Bennett 7200ae and Puritan-Bennett 840; Tyco Healthcare; Mansfield, MA). Inspiratory delay time and inspiratory trigger pressure were analyzed. Fio(2) at the airway opening and inside the model lung were evaluated during BiPAP S/T-D ventilation at supplemental oxygen flows of 3, 6, 9, 12 and 15 L/min. Measured oxygen concentration was compared to mathematically predicted levels. Finally, using two heated humidifiers, we evaluated the effect of gas leak on humidification. RESULTS: The bilevel pressure ventilators triggered properly at all levels of gas leak, and inspiratory triggering was more effective than with the ICU ventilators. Delivered Fio(2) with the BiPAP S/T-D ventilator was affected by gas leak and could be predicted mathematically unless the gas leak was large. With large gas leaks, although relative humidity was maintained, absolute humidity decreased. CONCLUSION: Gas leak affected triggering of ICU ventilators, Fio(2) of the BiPAP S/T-D ventilator, and humidity with both types of humidifiers.

Equipment Design↗

PubMed2005

[A case of continuous infusion of milrinone during continuous venovenous hemofiltration causing high plasma concentration of milrinone].

A 79-year-old woman was undergoing chronic hemodyalysis. She received a continuous infusion of milrinone of 0.25 microg x kg(-1) x min(-1) for 77 hours, 0.2 microg x kg(-1) x min(-1) for 39 hours and 0.1 microg x kg(-1) x min(-1) for one hour due to heart failure after mitral valve repair. While receiving continuous infusion of milrinone, she was undergoing continuous venovenous hemofiltration. After infusion of milrinone for three days no arrhythmia was seen except atrial fibliration, but blood pressure remained low. After stopping infusion of milrinone, the plasma concentration of milrinone was 792.7 ng x ml(-1) (therapeutic plasma concentration: 100-200 ng x ml(-1)). Now few data are available regarding the pharmacokinetic of milrinone in patients with severe renal failure and during CVVH. Therefore we should design a dose modification for intravenous milrinone in renal failure patients.

Aged↗

PubMed2004

Xenon suppresses nociceptive reflex in newborn rat spinal cord in vitro; comparison with nitrous oxide.

Although analgesic action of xenon has been reported, little is known about the effect of xenon at the spinal cord, which plays a crucial role in nociceptive transmission. We studied the effect of xenon on nociceptive reflex (the slow ventral root potential) and the monosynaptic reflex in neonatal rat spinal cord in vitro in comparison with nitrous oxide. Xenon (30%) and nitrous oxide (30%) were applied for 17 min through superfusing artificial cerebrospinal fluid. Xenon and nitrous oxide significantly reduced the amplitude of nociceptive reflex by approximately 70% and approximately 25%, respectively. Xenon and nitrous oxide also significantly reduced the amplitude of the monosynaptic reflex by approximately 35% and approximately 15%, respectively. These results indicate that xenon suppressed the synaptic transmission at the spinal cord, especially those of the slow ventral root potential, which reflect nociceptive transmission.

Animals↗

PubMed2004

In vitro inhibition of recombinant ligand-gated ion channels by high concentrations of milnacipran.

RATIONALE: Tricyclic antidepressants are known to inhibit various ligand-gated ion-channel (LGIC) receptors, and some of their clinical features may be associated with this activity. The effects of milnacipran, a selective inhibitor of the reuptake of serotonin and noradrenaline, on LGIC receptors have not yet been investigated on such ion-channel receptors. OBJECTIVES: To determine the in vitro effect of milnacipran on four recombinant LGIC receptors, nicotinic acetylcholine, N-methyl-D-aspartate, gamma-amino butyric acid (GABA) and 5-hydroxytryptamine3A receptors. METHODS: Receptors were expressed in Xenopus oocytes and LGIC activity measured using a two-voltage clamp technique. RESULTS: There was no interaction at the GABA receptor. The results at the other LGIC receptors showed that they could be inhibited by high concentrations of milnacipran. CONCLUSIONS: At high concentrations, milnacipran can inhibit certain LGICs. It is, however, unlikely that these interactions have any clinical consequence under normal therapeutic conditions, since the concentrations required are considerably higher than those achieved in plasma of treated patients.

Animals↗

PubMed2004

Electroencephalographic bicoherence is sensitive to noxious stimuli during isoflurane or sevoflurane anesthesia.

BACKGROUND: The authors previously reported changes in electroencephalographic bicoherence during isoflurane anesthesia combined with epidural anesthesia. Here, they examined the influence of noxious stimuli on electroencephalographic bicoherence as well as on the Bispectral Index (BIS) and the 95% spectral edge frequency (SEF95). METHODS: The authors enrolled 48 elective abdominal surgery patients (aged 22-77 years; American Society of Anesthesiologists physical status I or II). Raw electroencephalographic signals as well as BIS and SEF95 were recorded on a computer using a BIS monitor (A-1050) and Bispectrum Analyzer (BSA) for BIS (the authors' original software). Using BSA for BIS, the authors evaluated the two peak heights of electroencephalographic bicoherence. Anesthesia was induced with 3 mg/kg thiopental and was maintained with, in air-oxygen, 1.0% isoflurane or 1.5% sevoflurane. After confirming the steady state, the authors recorded baseline values. In experiment 1, they administered 3 microg/kg fentanyl 5 min after incision and investigated the changes in electroencephalographic derivatives at 5 and 10 min after incision. In experiment 2, they administered a similar dose of fentanyl 5 min before incision and investigated the changes in electroencephalographic derivatives immediately before and 5 min after incision. RESULTS: In experiment 1, after incision, both peak heights of electroencephalographic bicoherence significantly decreased but returned to control values after fentanyl administration. By contrast, after incision, BIS and SEF95 showed individual variability. In experiment 2, although fentanyl itself did not affect all electroencephalographic derivatives before incision, the variables remained unchanged after incision. CONCLUSION: Noxious stimuli decreased the peak heights of electroencephalographic bicoherence, an effect that was counteracted by fentanyl analgesia.

Adult↗

PubMed2004

Inhibitory effect of glucocorticoids on human-cloned 5-hydroxytryptamine3A receptor expressed in xenopus oocytes.

BACKGROUND: Methylprednisolone, dexamethasone, and other glucocorticoids have been found effective against nausea and vomiting induced by chemotherapy and surgery. Although the specific 5-hydroxytriptamine3 (5-HT3) receptor antagonists such as ondansetron and ramosetron are used as antiemetics, reports show that the use of 5-HT3 receptor antagonists with some glucocorticoids brings additional effects. Glucocorticoids are reported to be antiemetic. The effect of glucocorticoids on 5-HT3 receptor, however, has not been well characterized. This study was designed to examine whether dexamethasone and methylprednisolone had direct effects on human-cloned 5-HT3A receptor expressed in Xenopus oocytes. METHODS: Homomeric human-cloned 5-HT3A receptor was expressed in Xenopus oocytes. The authors used the two-electrode voltage-clamping technique to study the effect of methylprednisolone and dexamethasone on 5-HT-induced current. RESULTS: Both dexamethasone and methylprednisolone concentration-dependently attenuated 5-HT-induced current. Dexamethasone inhibited 2 microm 5-HT-induced current, which was equivalent to EC30 concentration for 5-HT3A receptor, with an inhibitory concentration 50% of 5.29 +/- 1.02 microm. Methylprednisolone inhibited 2 microm 5-HT-induced current with an inhibitory concentration 50% of 1.07 +/- 0.15 mm. The mode of inhibition with either dexamethasone or methylprednisolone was noncompetitive and voltage-independent. When administered together with the 5-HT3 receptor antagonists, ramosetron or metoclopramide, both glucocorticoids showed an additive effect on 5-HT3 receptor. CONCLUSION: The glucocorticoids had a direct inhibitory effect on 5-HT3 receptors. The combined effect of glucocorticoids and the 5-HT3 receptor antagonists seems additive.

Animals↗

PubMed2004

Effects of peak inspiratory flow on development of ventilator-induced lung injury in rabbits.

BACKGROUND: A lung-protecting strategy is essential when ventilating acute lung injury/acute respiratory distress syndrome patients. Current emphasis is on limiting inspiratory pressure and volume. This study was designed to investigate the effect of peak inspiratory flow on lung injury. METHODS: Twenty-four rabbits were anesthetized, tracheostomized, ventilated with a Siemens Servo 300, and randomly assigned to three groups as follows: 1) the pressure regulated volume control group received pressure-regulated volume control mode with inspiratory time set at 20% of total cycle time, 2) the volume control with 20% inspiratory time group received volume-control mode with inspiratory time of 20% of total cycle time, and 3) the volume control with 50% inspiratory time group received volume-control mode with inspiratory time of 50% of total cycle time. Tidal volume was 30 ml/kg, respiratory rate was 20 breaths/min, and positive end-expiratory pressure was 0 cm H2O. After 6 h mechanical ventilation, the lungs were removed for histologic examination. RESULTS: When mechanical ventilation started, peak inspiratory flow was 28.8 +/- 1.4 l/min in the pressure regulated volume control group, 7.5 +/- 0.5 l/min in the volume control with 20% inspiratory time group, and 2.6 +/- 0.3 l/min in the volume control with 50% inspiratory time group. Plateau pressure did not differ significantly among the groups. Gradually during 6 h, Pao2 in the pressure regulated volume control group decreased from 688 +/- 39 to a significantly lower 304 +/- 199 mm Hg (P < 0.05) (mean +/- SD). The static compliance of the respiratory system for the pressure regulated volume control group also ended significantly lower after 6 h (P < 0.05). Wet to dry ratio for the pressure regulated volume control group was larger than for other groups (P < 0.05). Macroscopically and histologically, the lungs of the pressure regulated volume control group showed more injury than the other groups. CONCLUSION: When an injurious tidal volume is delivered, the deterioration in gas exchange and respiratory mechanics, and lung injury appear to be marked at a high peak inspiratory flow.

Air Pressure↗

PubMed2004

Prophylactic effect of intravenous nicorandil on perioperative myocardial damage in patients undergoing off-pump coronary artery bypass surgery.

Nicorandil, ATP sensitive potassium channel opener, is shown to reduce coronary events for patients with stable angina. The present study was designed to examine the protective potential of nicorandil for patients undergoing off-pump coronary artery bypass grafting. Twenty-four patients undergoing off-pump coronary artery bypass grafting were randomly assigned to two groups, one receiving continuous infusion of nicorandil (1.0 microg.kg(-1).min(-1)) (n = 12) through anesthesia to next day and the other receiving no nicorandil for control (n = 12). For assessing myocardial injury, heart type fatty acid binding protein, troponin T, and creatine kinase MB isoform were determined during the first 15 hours after reperfusion. The concentration of heart type fatty acid binding protein in the nicorandil group was significantly lower than that in the control group. On the other hand, the concentrations of troponin T and creatine kinase MB isoform in the nicorandil group were lower than those in the control group, but the differences did not reach statistical significance. Furthermore, nicorandil did not affect the patients' hemodynamic variables. Our data suggest that the infusion of nicorandil provides small myocardial protection without affecting hemodynamic parameters during perioperative treatment of patients undergoing off-pump coronary artery bypass grafting.

Aged↗

PubMed2003

The neuroprotective effect of ONO-1714 on NMDA-mediated cytotoxicity in vitro.

We report the effects of a newly developed NOS inhibitor on the neurotoxicity induced by NMDA on cultured fetal rat cortical neurons. To date, three different isoforms of NOS have been characterized. It has been considered that both neuronal NOS and inducible NOS activities are detrimental to the ischemic brain, whereas endothelial NOS plays a prominent role in maintaining cerebral blood flow and prevents neuronal injury during ischemia. ONO-1714 is a newly developed competitive NOS inhibitor that has selective inhibitory potency for iNOS than eNOS. However, its effect on nNOS has not been investigated yet. In this study, we investigated the neuroprotective effect of ONO-1714 on NMDA-induced neurotoxicity in our established model of primary cultured cortical neurons of rat foetus. Cortical neurons (prepared from E16 rat foetuses) were used after 13-14 days in culture. The cells were exposed to 30 muM NMDA for 24 h in the culture. To evaluate the neuroprotective effects of NOS inhibitors, ONO-1714 and L-NAME, neurons were exposed to various concentrations of an NOS inhibitor with 30 muM NMDA. The NMDA induced neurotoxicity was significantly attenuated by ONO-1714 in all concentrations, but not in low to moderate concentrations of L-NAME. These findings demonstrate that the neuroprotective effect of ONO-1714 was more potent than L-NAME. Moreover, ONO-1714 has a strong inhibitory effect on nNOS and would be a powerful tool for the protection of neurons against cerebral ischemia.

Amidines↗

PubMed2003

Does the tube-compensation function of two modern mechanical ventilators provide effective work of breathing relief?

OBJECTIVE: An endotracheal tube (ETT) imposes work of breathing on mechanically ventilated patients. Using a bellows-in-a-box model lung, we compared the tube compensation (TC) performances of the Nellcor Puritan-Bennett 840 ventilator and of the Dräger Evita 4 ventilator. MEASUREMENTS AND RESULTS: Each ventilator was connected to the model lung. The respiratory rate of the model lung was set at 10 breaths/min with 1 s inspiratory time. Inspiratory flows were 30 or 60 l/min. A full-length 8 mm bore ETT was inserted between the ventilator circuit and the model lung. The TC was set at 0%, 10%, 50%, and 100% for both ventilators. Pressure was monitored at the airway, the trachea, and the pleura, and the data were recorded on a computer for later analysis of the delay time, of the inspiratory trigger pressure, and of the pressure-time product (PTP). The delay time was calculated as the time between the start of inspiration and minimum airway pressure, and the inspiratory trigger pressure was defined as the most negative pressure level. The same measurements were performed under pressure support ventilation of 4 and 8 cmH2O. The PTP increased according to the magnitude of inspiratory flow. Even with 100% TC, neither ventilator could completely compensate for the PTP imposed by the ETT. At 0% TC the PTP tended to be less with the Nellcor Puritan-Bennett 840 ventilator, while at 100% TC the PTP tended to be less with the Dräger Evita 4 ventilator. A small amount of pressure support can be equally effective to reduce the inspiratory effort compared with the TC. CONCLUSION: Although both ventilators provided effective TC, even when set to 100% TC they could not entirely compensate for a ventilator and ETT-imposed work of breathing. The effect of TC is less than that of pressure support ventilation. Physicians should be aware of this when using TC in weaning trials.

Humans↗

PubMed2003

Long-lasting effect of transcutaneous electrical nerve stimulation on the thermal hyperalgesia in the rat model of peripheral neuropathy.

We demonstrate here unexpectedly long-lasting effect of transcutaneous electrical nerve stimulation (TENS) to alleviate thermal hyperalgesia in rats with peripheral neuropathy produced by constriction of sciatic nerve. For TENS groups, electrical stimulation for 16.7 min (1 Hz, paired current, 12 mA, 5-ms interval, 0.2-ms duration, 999 pairs), once a day, was delivered for 5 consecutive days, under halothane anesthesia (Hal-TENS group) or pentobarbital anesthesia (Pent-TENS group). For non-TENS groups, only the anesthesia was delivered (Hal-no TENS group, Pent-no TENS group). For the control group, neither anesthetics nor TENS was delivered. To evaluate hyperalgesia, paw withdrawal latency (PWL) to radiant heat was measured before nerve constriction and five times after the constriction; just before TENS and at 1, 3, 7, and 14 days after the completion of TENS. Compared to the non-TENS groups, rats in the TENS groups showed significantly reduced thermal hyperalgesia at least for 3 days (Pent-TENS group) or for 7 days (Hal-TENS group) after TENS. These results indicate a possible long-lasting therapeutic effect of TENS applied under general anesthesia.

Anesthetics, Inhalation↗

PubMed2003

Effects of deep hypothermia on nitric oxide-induced cytotoxicity in primary cultures of cortical neurons.

Nitric oxide (NO) is thought to play a major role during cerebral ischemia. However, the protective efficacy of hypothermia against NO-induced neurotoxicity remains to be examined. In the present study, the degree of neurotoxicity induced by NO was analyzed in two temperature groups (normothermia, 37 degrees C; deep hypothermia, 22 degrees C) of cultured E16 Wistar rat cortical neurons. Two different NO donors, 1-hydroxy-2-oxo-3-(N-ethyl-2-aminoethyl)-3-ethyl-1-triazene (NOC-12) and 1-hydroxy-2-oxo-3-(3-amynopropyl)-3-isopropyl-1-triazene (NOC-5), that have equal half-lives at 37 degrees C and 22 degrees C, respectively, were used. Cultured neurons in each temperature group were exposed to 30 and 100 micro M NOC for three different time courses, 6 hr, 12 hr, and 24 hr. The survival rates of neurons were evaluated by assessing viable neurons on photomicrographs before and after the experiments. The highest survival rate (approximately 93%) was seen in both temperature groups when neurons were exposed to 30 micro M NOC for 6 hr and 12 hr, and there was no significant difference observed between these two groups (P > 0.05). Almost equal survival rates were observed in both temperature groups following exposure to 30 micro M NOC for 24 hr (at 37 degrees C, 80.4% +/- 2.6%; at 22 degrees C, 83.2% +/- 1.6%; P > 0.05). During exposure to 100 micro M NOC, although the survival rate linearly decreased (approximately from 70% to 5%) in both temperature groups when exposed for 6-24 hr, there were no significant intergroup differences observed (P > 0.05). In conclusion, hypothermia does not provide adequate protection to the neurons by acting on the mechanisms evoked by NO, so we speculate that hypothermia may not confer neuroprotetcion once NO is released during ischemia.

Animals↗

PubMed2003

Evidence for the involvement of GABA(A) receptor blockade in convulsions induced by cephalosporins.

There is accumulating evidence that most beta-lactam antibiotics (i.e., cephalosporins and penicillins) have some degree of convulsive activity, both in laboratory animals as well as in clinical settings. The proposed mechanism is suppression of inhibitory postsynaptic responses, mainly mediated by gamma-amino butyric acid (GABA)(A)-receptors (GABA(A)-R). However, comprehensive studies on the convulsive activities of various beta-lactam antibiotics in vivo and in vitro have not been performed. We have therefore examined the convulsive activities of seven different cephalosporins using both in vivo and in vitro models: intracerebroventricular (ICV) administration in mouse; [(3)H]muscimol binding assay (BA) in mouse brain synaptosome; and inhibition of recombinant mouse alpha1beta2gamma2s GABA(A)-Rs in Xenopus oocyte (GR). The rank orders of convulsive activities in mouse (cefazolin>cefoselis>cefotiam>cefpirome>cefepime>ceftazidime>cefozopran) correlated with those of inhibitory potencies on [(3)H]muscimol binding and GABA-induced currents of GABA(A)-R in vitro, with correlation coefficients of ICV:GR, ICV:BA and BA:GR of 0.882, 0.821 and 0.832, respectively. In contrast, none of the antibiotics had affinities for N-methyl-D-aspartate (NMDA) receptors nor facilitatory actions on NMDA receptor-mediated current in oocytes. These results clearly demonstrate that the mechanism of cephalosporin-induced convulsions is mediated predominantly through the inhibition of GABA(A)-R function and not through NMDA receptor modulation.

Animals↗

PubMed2003

Local anaesthetics have different mechanisms and sites of action at the recombinant N-methyl-D-aspartate (NMDA) receptors.

(1) Although the principal pharmacological targets of local anaesthetics (LAs) are voltage-gated Na(+) channels, other targets have also been suggested. Here we examined the effects of LAs on the N-methyl-D-aspartate (NMDA) receptor, a receptor involved in the process of nociception. (2) LAs (bupivacaine, lidocaine, procaine, and tetracaine) reversibly and concentration-dependently inhibited recombinant epsilon1/zeta1 and epsilon2/zeta1 NMDA receptors expressed in Xenopus oocytes (IC(50)s for bupivacaine, lidocaine, procaine, and tetracaine were 1032.0, 1174.1, 642.1 and 653.8 micro M at the epsilon1/zeta1 receptor; and 1090.8, 1821.3, 683.0 and 662.5 micro M respectively (at the epsilon2/zeta1 receptor). Bupivacaine and procaine were non-competitive antagonists; bupivacaine possesses non-competitive and competitive actions when interacting with glycine, whereas procaine has only non-competitive action. (3) Mutation of asparagine residue at position 598 (Asp(598)) in the zeta1 subunit, a residue associated with the blockade site for Mg(2+) and ketamine, to glutamine or arginine reduced the sensitivity to procaine but not to bupivacaine. Thus, procaine may interact with sites of action that are closely related to those of Mg(2+) and ketamine blockade. (4) These results suggest that LAs inhibit the NMDA receptor by various mechanisms.

Anesthetics, Local↗

PubMed2003

Nitrous oxide and xenon inhibit the human (alpha 7)5 nicotinic acetylcholine receptor expressed in Xenopus oocyte.

The neuronal nicotinic acetylcholine (nACh) receptor is one of the ligand-gated ion channels that regulate the synaptic release of neurotransmitters in the central nervous system. Recently, neuronal nACh receptors have received attention as a potential target for general anesthetics because many general anesthetics inhibit their functions at clinical concentrations. Several general anesthetics are known to inhibit the homomeric (alpha(7))(5) nACh receptor, a subtype of neuronal nACh receptors, but the effects of two gaseous anesthetics, nitrous oxide (N(2)O) and xenon (Xe), remain unknown. Using the two-electrode voltage-clamping technique, we investigated the effects of N(2)O and Xe at the human (alpha(7))(5) nACh receptor expressed in Xenopus oocytes. At clinically relevant concentrations, N(2)O and Xe reversibly inhibited the ACh-induced currents of the (alpha(7))(5) nACh receptor in a concentration-dependent manner. The inhibitory actions of both anesthetics at the (alpha(7))(5) nACh receptor were noncompetitive and voltage-independent. Our results suggest that inhibition of the (alpha(7))(5) nACh receptor by N(2)O and Xe may play a role in their anesthetic effects.

Anesthetics, Inhalation↗

PubMed2003

A small preoperative test dose of intravenous fentanyl can predict subsequent analgesic efficacy and incidence of side effects in patients due to receive epidural fentanyl.

UNLABELLED: Because individual variation is a likely factor affecting both the incidence and severity of side effects and the analgesic efficacy of epidural opioids, assessment of individual variation could be useful in deciding optimal dosage. By evaluating the response to a small test dose of IV fentanyl, we designed this study to predict the degree of pain relief and the incidence of side effects in patients who would be receiving postoperative epidural fentanyl. Before the induction of anesthesia, 50 micro g of fentanyl was administered IV, and 2 min after fentanyl, the patient response was evaluated. Twenty-three patients, who reported nausea, sleepiness, dizziness, sensation of warmth, and other symptoms, were categorized as responders (Group R); the remaining 20 patients were categorized as nonresponders (Group NR). At the completion of surgery, infusion of epidural fentanyl was administered (0.3 mg/d in 0.25% bupivacaine) for 96 h. At postoperative Hours 6 and 24, Group R had significantly lower visual analog scale scores for postoperative pain intensity and required fewer analgesics than Group NR. The incidence of side effects, however, was 74% for Group R and 10% for Group NR (P < 0.05), and side effects were more serious in Group R. This study demonstrates that preoperative administration of a small dose of fentanyl during the induction of anesthesia enables prediction of the analgesic efficacy of postoperative epidural fentanyl and the incidence and severity of side effects. IMPLICATIONS: Preoperative administration of a small dose of fentanyl during the induction of anesthesia enables prediction of the analgesic efficacy of postoperative epidural fentanyl and the incidence and severity of side effects.

Aged↗