Primary Human Lung Alveolus-on-a-chip Model of Intravascular Thrombosis for Assessment of Therapeutics.

Pulmonary thrombosis is a significant cause of patient mortality; however, there are no effective in vitro models of thrombi formation in human lung microvessels that could also assess therapeutics and toxicology of antithrombotic drugs. Here, we show that a microfluidic lung alveolus-on-a-chip lined by human primary alveolar epithelium interfaced with endothelium and cultured under flowing whole blood can be used to perform quantitative analysis of organ-level contributions to inflammation-induced thrombosis. This microfluidic chip recapitulates in vivo responses, including platelet-endothelial dynamics and revealed that lipopolysaccharide (LPS) endotoxin indirectly stimulates intravascular thrombosis by activating the alveolar epithelium, rather than acting directly on endothelium. This model is also used to analyze inhibition of endothelial activation and thrombosis due to a protease activated receptor-1 (PAR-1) antagonist, demonstrating its ability to dissect complex responses and identify antithrombotic therapeutics. Thus, this methodology offers a new approach to study human pathophysiology of pulmonary thrombosis and advance drug development.

Diabetes attenuates the minimum anaesthetic concentration (MAC) and MAC-blocking adrenergic response reducing actions of clonidine in rats.

BACKGROUND: It is well known that clonidine, an alpha2 agonist, reduces anaesthetic requirement and attenuates haemodynamic responses against noxious stimuli. However, the diabetic state is known to affect several functions of alpha2 adrenoceptors. We investigated the effects of streptozotocin (STZ)-induced diabetes mellitus (DM) on these beneficial actions of clonidine in halothane-anaesthetized rats. METHODS: The rats were randomly assigned to one of three groups: diabetes (n=24, induced by 50 mg x kg(-1) IV STZ), diabetes treated with insulin (n=24), or control (n=24). We evaluated the effects of clonidine on minimum anaesthetic concentration (MAC) and minimum concentration of halothane needed to suppress cardiovascular responses evoked by a noxious stimulus (MAC-blocking adrenergic responses: MAC-BAR) in each group. MAC and MAC-BAR of halothane were determined by the tail clamp method. MAC-BAR was defined as the MAC which attenuated haemodynamic responses within 10% following the tail clamp. RESULTS: The diabetic state decreased MAC of halothane by approximately 10%, while MAC-BAR of halothane had been little affected. In the diabetes group, MAC reducing action of clonidine (30 and 100 microg x kg(-1), IV) was completely abolished and MAC-BAR reducing action of clonidine was partially reduced (30 but not 100 microg x kg(-1), IV). Insulin treatment preserved these actions of clonidine. CONCLUSION: It is suggested that the diabetic state attenuates the beneficial actions of clonidine and that insulin treatment of diabetes preserves these actions of clonidine.

[Transthoracic radical esophagectomy after extensive myocardial infarction].

We experienced the perioperative management of a 47 year-old patient for transthoracic esophagectomy after myocardial infarction. He was admitted to our hospital and diagnosed as having advanced esophageal cancer and he developed extensive myocardial infarction on the day of admission. Revascularization with PTCA was not successful, and circulatory support (IABP) was required for 7 days. Complete occlusion of the right coronary artery and extensive akynesis of the right ventricle occurred. Two months later, transthoracic esophagectomy was scheduled. The patient was monitored with pulmonary artery catheter during perioperative period. The postoperative course was uneventful and the patient was discharged 64 th day after the operation.

[Monitoring of cerebral oxygenation status with near-infrared spectroscopy during inferior vena caval reconstruction under extracorporeal circulation].

We report two cases of anesthetic management with monitoring by near-infrared spectroscopy in patients with renal cell carcinoma and with adrenal cortical carcinoma, who had tumor thrombus invading into the inferior vena cava. In inferior vena caval reconstruction, extracorporeal circulation such as veno-veno bypass or cardiopulmonary bypass is frequently required. The hemodynamic unstability under extracorporeal circulation may lead to severe cerebral damage, especially in elderly patients. We monitored cerebral oxygenation state during reconstruction of the vena cava by near-infrared spectroscopy. One patient underwent surgery with veno-veno bypass and another patient with partial cardiopulmonary bypass. Oxygenated hemoglobin decreased during extracorporeal circulation, especially during the use of partial cardiopulmonary bypass compared with veno-veno bypass. However, these decreased oxygenated hemoglobin was restored rapidly at the end of extracorporeal circulation. Both patients showed no post-operative neurological complication. We concluded that near-infrared spectroscopy, which is continuous and non-invasive monitoring of cerebral oxygenation status, is one of the useful monitors during extracorporeal circulation.

A study of 13 patients with gastric tube in place after esophageal resection: use of omeprazole to decrease gastric acidity and volume.

STUDY OBJECTIVE: To investigate whether oral omeprazole 20 mg decreases the risk of aspiration pneumonia in patients with gastric tube reconstruction. DESIGN: Consecutive study. SETTING: Operation room of cancer center. PATIENTS: Thirteen patients with gastric tube reconstruction for esophageal cancer. INTERVENTIONS: Oral omeprazole 20 mg was given the night before surgery. A rapid-sequence induction with cricoid pressure was employed for induction of anesthesia. After tracheal intubation, a nasogastric catheter was inserted into the gastric tube and the contents were aspirated. MEASUREMENTS AND MAIN RESULTS: The pH and volume of the gastric contents were measured. The pH and volume of the gastric tube contents were 4.5 +/- 1.6 (range from 2.5 to 7.0) and 9.5 +/- 10.2 mL (range from 0 to 30 mL), respectively. Food residue was recognized in nine patients. There was no patient with a pH below 2.5 and a volume of 25 mL or greater. CONCLUSIONS: Omeprazole 20 mg decreased the acidity and volume of the gastric tube contents and reduced the risk of aspiration pneumonia in patients with a gastric tube in place.

[Usefulness of a simple expiratory gas monitor during sedation under spinal anesthesia].

We introduce a simple expiratory gas monitor during sedation under spinal anesthesia. A small extension tube for infusion used as a gas sampling line is placed in the nasal vestibule. It is necessary to make it sure that the point of the tube should not contact with the mucous membrane of the nose. Our method needs no special equipments such as Capnoxygen or Nazorcap, but a cheap extension tube available in any operating room. Therefore this is a simple method. Expiratory gas monitor can detect apnea early, airway obstruction and stenosis and predict PaCO2 during sedation. The change of fractional concentration of oxygen in inspired gas predicts the change of tidal volume. Increase in the former reflects a decrease in the latter under the administration of oxygen. It is possible to evaluate whether sedation became steady with analysis of respiratory pattern. However, nasal discharge may interrupt monitoring expiratory gas. Our simple method to monitor expiratory gas is useful during sedation under regional anesthesia.

Premedication modifies the quality of sedation with propofol during regional anesthesia.

PURPOSE: To determine the effects of diazepam or clonidine on the quality of sedation with propofol during regional anesthesia. METHODS: In a prospective randomised, controlled, double-blinded study, 60 patients undergoing elective gynecological surgery were studied. They were given premedication with 0.15-mg clonidine (Group-CL, n=20), 5-mg diazepam (Group-DZ, n = 20), or placebo (Group-P, n = 20) po. After spinal anesthesia was established, sedation was provided with propofol and controlled using a five-point sedation score at 3, "eyes closed but rousable to command", and 4, "eyes closed but rousable to mild physical stimulation". During sedation, blinded anesthesiologist recorded occurrence of complications. At two hours after end of sedation, patients were asked if they had intraoperative dream and memory. RESULTS: The loading dose, steady-state infusion rate, and overall mean infusion rate in Group-CL were 0.80 mg x kg(-1), 2.35 mg x kg(-1) x hr(-1) and 2.89 mg x kg(-1) x hr(-1), compared with 0.97 mg x kg(-1), 3.13 mg x kg(-1) x hr(-1) and 3.59 mg x kg(-1) x hr(-1) in Group-DZ, and 1.38 mg x kg(-1), 4.10 mg x kg(-1) x hr(-1) and 4.36 mg x kg(-1) x hr(-1) in Group-P, respectively. Indices of both Group-CL (P < 0.001) and Group-DZ (P < 0.05) were smaller than those of Group-P Moreover, clonidine reduced the incidence of uncontrolled movement (P < 0.01), while diazepam reduced the incidence of intraoperative memory and increased the incidence of dream (P < 0.05). Premedication did not affect the incidence of other complications. CONCLUSION: Both premedicants reduced propofol requirements and exerted beneficial effects on the incidence of some complications during sedation with propofol as an adjunct to regional anesthesia.

Arrhythmogenic effect of hypercapnia in ducks anesthetized with halothane.

OBJECTIVE: To determine effects of hypercapnia on arrhythmias in ducks anesthetized with halothane. ANIMALS: 12 ducks, 6 to 8 months old, weighing 1.1 to 1.6 kg. PROCEDURES: Each duck was anesthetized with a 1.5% mixture of halothane in oxygen, and anesthetic depth was stabilized during a 20-minute period. We added CO2 to the inspired oxygen to produce CO2 partial pressures of 40, 60, and 80 mm Hg in the inspired gas mixture.The CO2 partial pressure was increased in a stepwise manner. When arrhythmias were not evident during inhalation of the gas mixture at a specific CO2 partial pressure, the CO2 partial pressure was maintained for 10 minutes before a sample was collected for blood gas analysis. When arrhythmias were detected, a sample for blood gas analysis was collected after the CO2 partial pressure was maintained for at least 2 minutes, and CO2 inhalation then was terminated. RESULTS: During the stabilization period, PaCO2 (mean +/- SD) was 33 +/- 5 mm Hg,and arrhythmias were not detected. In 6 ducks, arrhythmias such as unifocal and multifocal premature ventricular contractions developed during inhalation of CO2. Mean PaCO2 at which arrhythmias developed was 67 +/- 12 mm Hg. In 5 of 6 ducks with arrhythmias, the arrhythmias disappeared after CO2 inhalation was terminated. CONCLUSION AND CLINICAL RELEVANCE: Analysis of data from this study indicated that hypercapnia can lead to arrhythmias in ducks during halothane-induced anesthesia. Thus, ventilatory support to maintain normocapnia is important for managing ducks anesthetized with halothane.

[Perioperative management for radical esophagectomy in a patient with polycythemia vera].

We experienced perioperative management of a 75 year-old patient with polycythemia vera (PV) who underwent transthoracic esophagectomy. After treatment for 14 days of ranimustine and hydroxycarbamid, the preoperative hemoglobin, hematocrit values and platelet count were 17.9 g.dl-1, 58% and 54 x 10(4).mm-3 respectively. During the perioperative period, phlebotomy, elastic stockings, intermittent pneumatic compression, infusion of nafamostat, and early extubation (the day of operation) were performed to prevent deep venous thrombosis. The postoperative course was uneventful and the patient was discharged 34 days after the operation.

[Effects of infusion methods of propofol on quality of sedation and ease of sedation control during gynecological laparotomy under spinal anesthesia].

Twenty patients were prospectively and randomly studied to investigate effects of infusion methods of propofol on quality of sedation and ease of sedation control during gynecological laparotomy under spinal anesthesia. After establishment of spinal anesthesia, patients were randomly assigned to one of the following two groups, i.e. conventional continuous infusion group (Cont group) and target-controlled infusion group (TCI group). In the Cont group, propofol was started at a rate of 6 mg.kg-1.hr-1 until response to command disappeared. In the TCI group, the initial target concentration of propofol was set at 1.2 micrograms.ml-1 until response to command disappeared. Thereafter infusion rate or target concentration was adjusted to maintain Mackenzie's score at 3 or 4. Predicted concentration of propofol was 1.2 +/- 0.01 micrograms.ml-1 at induction of sedation and 1.2 +/- 0.11 micrograms.ml-1 during stable sedation in the TCI group. Satisfaction VAS, anxiety VAS, discomfort VAS, sedation score and times of changing infusion condition were similar in both groups. Total dose of propofol was significantly less in the TCI group. In conclusion, quality of sedation and ease of control of sedation were comparable in both groups and continuous infusion method is simple.

[Anesthesia for MIDCAB (minimally invasive direct coronary bypass) in a patient with Tangier disease: a case report].

Tangier disease is a rare, autosomally-inherited disorder of lipoprotein metabolism characterized by absence or marked deficiency of normal high density lipoprotein (HDL) cholesterol in plasma resulting in the accumulation of cholesteryl esters in various organs. The patient was a 55-yr-old male diagnosed as Tangier disease 16 years before. He had angina on exercise and his coronary angiogram revealed triple vessel disease including left main trunk (LMT) lesion. Stenosis of the right coronary artery was treated by percutaneous transluminal coronary angioplasty (PTCA). He was scheduled for a MIDCAB for further PTCA to be performed to relieve the stenosis of LMT. Preoperative laboratory data and physical examination showed total cholesterol 36 mg.dl-1, HDL-cholesterol 2 mg.dl-1, apoprotein A-I not-detected, pancytopenia, hyperplastic orange tonsils, splenomegaly and hepatomegaly. Clonidine 0.225 mg was orally given as a preanesthetic medication. Anesthesia was induced with fentanyl and midazolam and maintained with propofol, sevoflurane and supplemental fentanyl. Nitroglycerin and diltiazem were infused continuously. ST segment was elevated transiently during the clamping of the left anterior descending branch. Hemodynamic parameters were stable during the operation. He was extubated 2 hours after the end of the operation. No significant changes were found in postoperative EKG, total cholesterol, HDL-cholesterol and triglyceride. Perioperative course was uneventful.

Supraspinal, not spinal, alpha(2) adrenoceptors are involved in the anesthetic-sparing and hemodynamic-stabilizing effects of systemic clonidine in rats.

UNLABELLED: Clonidine, an alpha(2) agonist, reduces the anesthetic requirement and attenuates harmful hemodynamic responses to noxious stimuli. We examined the responsible sites of action in the central nervous system for the minimum alveolar anesthetic concentration (MAC) and MAC blocking adrenergic response (MAC-BAR) reducing effects of systemically administered clonidine in halothane-anesthetized rats. The MAC for halothane was determined by the tail clamp method, and MAC-BAR was defined as the MAC which attenuated hemodynamic responses within 10% after the tail clamp. We examined the effect of IV clonidine in the presence of rauwolscine, an alpha(2) antagonist given through IV, intrathecal (IT), intracisternal (IC), or intracerebroventrical (ICV) routes. IV clonidine reduced MAC and MAC-BAR dose-dependently. IV and ICV rauwolscine antagonized the MAC-reducing effect of clonidine, whereas IC and IT rauwolscine did not. In comparison, IV, ICV, and IC rauwolscine antagonized the MAC-BAR-reducing effect of clonidine; IT rauwolscine had no effect. Our data demonstrate that the alpha(2) adrenoceptors in the regions above mesencephalon and both the regions above mesencephalon and the lower brainstem are responsible for the MAC and MAC-BAR-reducing effect of systemic clonidine in rats, respectively. However, the spinal alpha(2) adrenoceptors were not involved in these effects of clonidine. IMPLICATIONS: In the regions above mesencephalon, alpha(2) adrenoceptors were the most responsible for the minimum alveolar concentration-reducing effect and both the lower brainstem and regions above mesencephalon were involved in the minimum alveolar concentration blocking adrenergic response-reducing effect of clonidine. The spinal alpha(2) adrenoceptors did not significantly contribute to these effects of clonidine.

Midazolam premedication reduces propofol requirements for sedation during regional anesthesia.

PURPOSE: Propofol is often used for sedation during spinal anesthesia. We investigated the effects of midazolam premedication on the propofol requirements and incidence of complications during sedation. METHODS: In a prospective randomized, controlled, and single-blinded study, 50 patients undergoing elective gynecological surgery were randomly divided into control and midazolam groups. Patients in the midazolam group received 2 mg midazolam im 30 min before arrival at the operation room. After spinal anesthesia was instituted with intrathecal injection of hyperbaric tetracaine, we provided sedation using continuous infusion of propofol. The level of sedation was controlled at a level between "eyes closed but rousable to command" and "eyes closed but rousable to mild physical stimulation" by adjusting the infusion rate. During sedation, the propofol requirements and complications were recorded and patients were asked, two hours after the end of operation, whether they remembered intraoperative events. RESULTS: In the midazolam group, the loading dose, steady state infusion rate, and overall infusion rate of propofol were 0.74 mg x kg(-1), 2.86 mg x kg(-1) x hr(-1), and 3.32 mg x kg(-1) x hr(-1), respectively, which were about 17% lower than those in the control group (P<0.05). Moreover, midazolam premedication reduced the incidence of intraoperative memory (P < 0.05), but had no effects on other complications. CONCLUSION: Midazolam premedication reduced propofol requirements and the incidence of intraoperative memory during sedation. These effects on sedation using propofol during spinal anesthesia are considered beneficial for patients.

Cooperation of fibronectin with lysophosphatidic acid induces motility and transcellular migration of rat ascites hepatoma cells.

We have previously shown that the transcellular migration of rat ascites hepatoma (AH130-MM1) cells through a cultured mesothelial cell monolayer (MCL) is triggered with lysophosphatidic acid (LPA) that stimulates actin polymerization and myosin light chain phosphorylation through the activation of Rho-ROCK (Rho-kinase) cascade. When, however, the motility of MM1 cells on a glass surface was tested by phagokinetic track motility assay, LPA failed to induce the motility. Nevertheless, when the glass had been coated with fibronectin (FN), LPA could induce phagokinetic motility which was accompanied by transformation of MM1 cells to fusiform-shape and assembly of focal adhesion. beta1 integrin, the counter receptor of FN, was expressed on MM1 cells. Anti-FN antibody, anti-beta1 integrin antibody and cyclo-GRGDSPA remarkably suppressed LPA-induced phagokinetic motility. These antibodies suppressed LPA-induced transcellular migration through MCL, as well. These results indicate that actin polymerization and phosphorylation of myosin light chain through Rho activation are insufficient for inducing motility but the cooperative FN/beta1 integrin-mediated adhesion is necessary for both the phagokinetic motility and transcellular migration of MM1 cells.

Oral clonidine reduces the requirement of prostaglandin E1 for induced hypotension.

PURPOSE: To determine the effects of preanesthetic oral clonidine on the dose of prostaglandin EI (PGEI) required to produce hypotension during anesthesia. METHOD: Oral placebo, 75 microg or 150 microg clonidine were administered 60 min prior to induction of anesthesia. Anesthesia was maintained with O2:N2O (30:70) and isoflurane 1.0%. After hemodynamic stabilization, an infusion of prostaglandin EI was started (0.05 microg x kg(-1) x min(-1)) and the rate of infusion was adjusted to maintain mean arterial pressure (MAP) between 60-70 mm Hg during operation. RESULTS: Duration of hypotension in placebo, 75 microg and 150 microg preanesthetic oral clonidine treated groups were 132+/-46, 117+/-37 and 129+/-56 min, respectively. The PGEI requirement in each group were 1563+/-180 (28.6+/-3.2), 594+/-197 (10.8+/-3.6) and 283+/-30 (5.5+/-3.6) microg (microg x kg(-1)), respectively. In addition, blood loss in each group were 1461+/-389, 805+/-240 and 931+/-40 ml, respectively. CONCLUSION: Preanesthetic oral clonidine decreased the dose of PGEI required to produce hypotension, and decreased the blood loss during operation.

Phosphodiesterase type III inhibitor, cilostazol, inhibits colon cancer cell motility.

Metastasis of cancer cells is initiated by the cellular migration into extracellular matrix and surrounding vessels. We previously showed that elevation of cAMP levels in cancer cells suppressed trans-cellular migration in vitro. Drugs that can elevate cAMP levels in cancer cells effectively may be applied to prevent metastasis in cancer patients. Cilostazol, an oral anti-platelet drug, is a specific cAMP phosphodiesterase type III inhibitor and has been clinically used to treat thrombosis patients. In chemotaxis assay, cellular migration of human colon cancer cells, DLD- 1, was induced by 10 microg/ml of soluble fibronectin or 10% of fetal bovine serum (FBS). Treatment with cilostazol (50 microM) suppressed 92.3% or 84.6% of the migration in control cells, respectively. When DLD-1 cells were stimulated by soluble fibronectin in phagokinetic assay, migration assessed by the area of gold particle phagocytosis track was induced and cilostazol also decreased 67.3% of the cellular migration in control cells. Furthermore, in the trans-cellular migration assay, cilostazol suppressed cancer cell invasion induced by FBS. Thus, cilostazol can suppress colon cancer cell motility and might be effective as an anti-metastasis drug for cancer patients.

Incidence of venous and paradoxical air embolism in neurosurgical patients in the sitting position: detection by transesophageal echocardiography.

BACKGROUND: Venous air embolism (VAE) and paradoxical air embolism (PAE) are serious complications associated with the sitting position for neurosurgery. Although PAE is the result of VAE, the incidence of PAE according to the severity of VAE has not been investigated systematically in humans. METHODS: Twenty-one patients scheduled for neurosurgery in the sitting position were investigated prospectively. VAE and PAE were continuously monitored by cardiac two-dimensional 4-chamber view using transesophageal echocardiography (TEE) and the severity of VAE and PAE was quantitatively graded from 0 to 3 by the microbubbles score. Haemodynamic parameters and end-tidal CO2 concentration (PETCO2) during VAE and PAE were also recorded. RESULTS: Microbubbles in the right atrium appeared in all patients and the number of patients involved in grades 0, 1, 2 and 3 of VAE was 0, 10, 3 and 8, respectively. PAE occurred in 3 patients and only followed grade 3 of VAE. PAE always appeared from 20 to 30 s after the most severe VAE. A reduction of PETCO2 and an increase of pulmonary artery pressure were noted during all episodes of grades 2 and 3 VAE. In contrast, a significant reduction of systemic blood pressure occurred in 1 case of grade 2 and 3 cases of grade 3. CONCLUSIONS: VAE detected by TEE appeared in all patients undergoing neurosurgery in the sitting position and PAE only occurred following the most severe grade of VAE. To prevent growth of VAE is an important prophylactic for PAE.

The effects of preanesthetic oral clonidine on total requirement of propofol for general anesthesia.

STUDY OBJECTIVE: To investigate the effects of preanesthetic oral clonidine on total propofol requirement for uniform minor surgery (breast conservative surgery: breast cancer removal with axillary lymph node dissection), and to compare the action of clonidine with that of preanesthetic oral diazepam, a commonly used benzodiazepine. DESIGN: Randomized double-blinded study. SETTING: Operating room ASA physical status I and II room and recovery room of the cancer center. PATIENTS: 80 breast cancer patients scheduled for surgery. INTERVENTIONS: Patients were randomized to one of four treatment groups (placebo, clonidine 75 micrograms, or 150 micrograms of clonidine, or 10 mg of diazepam were orally administered 60 min before induction of anesthesia); n = 20 per group. After evaluating the sedation and anxiety levels of patients using a visual analog scale, anesthesia was induced with propofol (1.5 mg/kg), and maintained with oxygen (O2): nitrous oxide (N2O) (30:70) with a continuous infusion of propofol. The propofol infusion was started at 10 mg/kg/h for 10 minutes, then decreased to 8 mg/kg/h, and 6 mg/kg/h thereafter, and the rate of infusion was adjusted to obtain adequate anesthesia (maintaining hemodynamic parameters within 20% of that prior to premedication). Fentanyl 0.2 mg (each 0.1 mg was given for intubation and axillary lymph node dissection, respectively) was administered. MEASUREMENTS AND MAIN RESULTS: Preanesthetic oral clonidine (150 micrograms) and diazepam (10 mg) induced anxiolysis without sedation. The total requirement (the mean infusion rates) of propofol in placebo, clonidine 75 micrograms, clonidine 150 micrograms, and 10 mg of diazepam groups were 841 +/- 70 (9.0 +/- 0.3), 720 +/- 63 (7.1 +/- 0.4), 491 +/- 39 (5.6 +/- 0.2), and 829 +/- 77 mg (7.9 +/- 0.4 mg/kg/h), respectively. The cost of propofol in these groups was $51.0 +/- 3.8, $45.5 +/- 3.2, $33.5 +/- 2.3, and $50.5 +/- 4.4, respectively. CONCLUSIONS: Preanesthetic oral clonidine (150 micrograms) but not diazepam (10 mg) reduced the total requirement of propofol while stabilizing hemodynamic parameters. In addition, 150 micrograms of oral clonidine attenuates the hemodynamic responses associated with tracheal intubation.

The effect of imidazoline receptors and alpha2-adrenoceptors on the anesthetic requirement (MAC) for halothane in rats.

BACKGROUND: Recent evidences have documented that several pharmacologic actions of alpha2-adrenoceptor agonists are mediated via activation of not only alpha2-adrenoceptors, but also by imidazoline receptors, which are nonadrenergic receptors in the central nervous system. However, the effect of imidazoline receptors on the anesthesia is not well known, and it is important to clarify the effects of both receptors on anesthesia. METHODS: Seventy-two rats were anesthetized with halothane, and the anesthetic requirement for halothane was evaluated as minimum alveolar concentration (MAC). The MAC for halothane was determined in the presence of dexmedetomidine (0, 10, 20, and 30 microg/kg, intraperitoneally [IP]), a selective alpha2-adrenoceptor agonist with weak affinity for imidazoline receptors. Then, the authors evaluated the inhibitory effect of rauwolscine (20 mg/kg, IP), an alpha2-adrenoceptor antagonist with little affinity for imidazoline receptors, on the MAC-reducing action of dexmedetomidine (30 microg/kg). Further, the effect of rilmenidine (20, 50, 100, 1000 microg/kg, IP), a selective imidazoline receptor agonist, on the MAC for halothane was also investigated. RESULTS: Dexmedetomidine decreased the MAC for halothane dose-dependently, and this MAC-reducing action of dexmedetomidine was completely blocked by rauwolscine. Rilmenidine alone did not change the MAC for halothane. CONCLUSIONS: The present data indicate that the anesthetic sparing action of dexmedetomidine is most likely mediated through alpha2- adrenoceptors, and the stimulation of imidazoline receptors exerts little effect on the anesthetic requirement for halothane.