Atomic-resolution imaging in liquid by frequency modulation atomic force microscopy using small cantilevers with megahertz-order resonance frequencies.

In this study, we have investigated the performance of liquid-environment FM-AFM with various cantilevers having different dimensions from theoretical and experimental aspects. The results show that reduction of the cantilever dimensions provides improvement in the minimum detectable force as long as the tip height is sufficiently long compared with the width of the cantilever. However, we also found two important issues to be overcome to achieve this theoretically expected performance. The stable photothermal excitation of a small cantilever requires much higher pointing stability of the exciting laser beam than that for a long cantilever. We present a way to satisfy this stringent requirement using a temperature controlled laser diode module and a polarization-maintaining optical fiber. Another issue is associated with the tip. While a small carbon tip formed by electron beam deposition (EBD) is desirable for small cantilevers, we found that an EBD tip is not suitable for atomic-scale applications due to the weak tip-sample interaction. Here we show that the tip-sample interaction can be greatly enhanced by coating the tip with Si. With these improvements, we demonstrate atomic-resolution imaging of mica in liquid using a small cantilever with a megahertz-order resonance frequency. In addition, we experimentally demonstrate the improvement in the minimum detectable force obtained by the small cantilever in measurements of oscillatory hydration forces.

Schwannoma of the esophagus: a case exhibiting high 18F-fluorodeoxyglucose uptake in positron emission tomography imaging.

Esophageal schwannoma is rare and it is difficult preoperatively to confirm a definitive diagnosis, even using current imaging techniques. We present a case of a benign esophageal schwannoma that was surgically excised and confirmed by immunohistochemical staining. Conventional radiological studies, including barium meal, computed tomography and endoscopic examination had shown a solid submucosal tumor of the upper thoracic esophagus but had been unable to confirm the diagnosis. Positron emission tomography was carried out to evaluate the malignant potential and showed a high uptake of 18F-fluorodeoxyglucose (FDG) into the tumor in both the early and delayed phase, suggesting that the tumor was a potentially malignant tumor such as a gastrointestinal stromal tumor. This is the first reported case of esophageal schwannoma that indicated a high FDG uptake. Although consensus has not been reached regarding the precise mechanism of FDG accumulation in schwannomas, we discuss our clinicopathological findings and review other studies of the subject.

Neonatal tactile stimulation reverses the effect of neonatal isolation on open-field and anxiety-like behavior, and pain sensitivity in male and female adult Sprague-Dawley rats.

It is well known that early life events induce long-lasting psychophysiological and psychobiological influences in later life. In rodent studies, environmental enrichment after weaning prevents the adulthood behavioral and emotional disturbances in response to early adversities. We compared the behavioral effect of neonatal isolation (NI) with the effect of NI accompanied by tactile stimulation (NTS) to determine whether NTS could reverse or prevent the effects of NI on the adulthood behavioral and emotional responses to environmental stimuli. In addition, we also examined the sex difference of the NTS effect. Measurements of body weights, an open-field locomotor test, an elevated plus maze test, a hot-plate test, and a contextual fear-conditioning test were performed on postnatal day 60. As compared with rats subjected to NI, rats subjected to NTS showed significantly higher activity and exploration in the open-field locomotor test, lower anxiety-like behavior in the elevated plus maze test, and significantly prolonged latencies in the hot-plate test, and this effect was equal among males and females. In the contextual fear-conditioning test, whereas NTS significantly reduced the enhanced freezing time due to NI in females, no significant difference in the freezing time between NI and NTS was found in males. These findings indicate that adequate tactile stimulation in early life plays an important role in the prevention of disturbances in the behavioral and emotional responses to environmental stimuli in adulthood induced by early adverse experiences.

Initial distribution volume of glucose is correlated with intrathoracic blood volume in hypovolaemia and following volume loading in dogs.

BACKGROUND AND OBJECTIVE: Initial distribution volume of glucose (IDVG) reliably measures the central extracellular fluid volume in the presence of fluid gain or loss. We hypothesized that IDVG has a close relationship with intrathoracic blood volume (ITBV), which has recently been used as an indicator of cardiac preload. We therefore examined whether IDVG can correlate with ITBV in various fluid volume states. METHODS: Fourteen anaesthetized mongrel dogs were mechanically ventilated. ITBV and cardiac output were measured by single transpulmonary thermodilution technique. IDVG and indocyanine green derived plasma volume (PV-ICG) were determined by the administration of 100 mg kg(-1) glucose and 0.5 mg kg(-1) indocyanine green solutions, respectively, and calculated by applying a one-compartment model. Three sets of measurements were performed before and after haemorrhage (30 mL kg(-1) and subsequent fluid volume loading (90 mL kg(-1) of lactated Ringer's solution). RESULTS: A linear correlation was observed between IDVG and ITBV (r2 = 0.52, n = 42, P < 0.001) and between PV-ICG and ITBV (r2 = 0.44, n = 42, P < 0.001) throughout the procedures. A linear correlation was also observed between changes in IDVG and those in ITBV (r2 = 0.76, n = 28, P < 0.001). The ITBV/IDVG ratio during normovolaemia was 0.26 +/- 0.04, which remained unchanged during the procedure. CONCLUSION: Results showed that that IDVG has a linear correlation with ITBV, and support the concept that IDVG measurement has potential as a surrogate measure of ITBV in various fluid volume states.

Isoflurane increases norepinephrine release in the rat preoptic area and the posterior hypothalamus in vivo and in vitro: Relevance to thermoregulation during anesthesia.

General anesthetics modulate autonomic nervous system function including thermoregulatory control, which resides in the preoptic area of the anterior hypothalamus. However, the mechanism by which anesthetics modulate hypothalamic function remains unknown. We hypothesized that isoflurane increases norepinephrine release in the preoptic area and in the posterior hypothalamus causing hypothermia during anesthesia. To test this hypothesis, we performed a series of in vivo and in vitro studies in rats. In vivo studies: 1) Norepinephrine release was measured by microdialysis in the preoptic area or the posterior hypothalamus (n=9 each) before, during (30 min), and after (50 min) rats were anesthetized with 2% isoflurane. 2) In five rats, blood gases and arterial pressure were measured. 3) Body temperature changes (n=6 each) were measured after prazosin (0, 0.05, 0.5 microg), norepinephrine (0, 0.1, 1.0 microg), or 0.5 microg prazosin with 1.0 microg norepinephrine injection into the preoptic area. In vitro study: Norepinephrine release was measured from anterior or posterior hypothalamic slices (n=10 each) incubated with 0, 1, 2, or 4% isoflurane in Ca2+-containing buffer or with 4% isoflurane (n=10) in Ca2+-free buffer. Data were analyzed with repeated measures or factorial ANOVA and Student-Newman-Keuls tests. P<0.05 was significant. During anesthesia, norepinephrine release in the preoptic area was increased approximately 270%, whereas the release in the posterior hypothalamus remained unchanged. During emergence, posterior hypothalamic norepinephrine release increased by approximately 250% (P<0.05). Rectal temperature changes correlated with norepinephrine release from the preoptic area. Norepinephrine in the preoptic area enhanced isoflurane-induced hypothermia, while prazosin reversed it. Norepinephrine release from anterior hypothalamic slices increased at all isoflurane concentrations, but only at the highest concentration in posterior hypothalamic slices. Under Ca2+-free conditions, 4% isoflurane increased norepinephrine from both regions. These results suggest that augmentation of norepinephrine release in the preoptic area is responsible for hypothermia during general anesthesia.

Repeatability of measurements of the initial distribution volume of glucose in haemodynamically stable patients.

AIMS: The initial distribution volume of glucose (IDVG) has been proposed to provide a useful tool to estimate the central extracellular fluid volume. The purpose of this study was to determine the repetition interval of two consecutive measurements in haemodynamically stable patients without presence of recent changes in fluid status. METHODS: Twenty-nine patients admitted to the general intensive care unit of the University of Hirosaki Hospital were entered into this study. After achieving a haemodynamically stable state in each patient regardless of an infusion of vasoactive drugs, two glucose challenges at an interval of either 30 or 60 min, were carried out to calculate the IDVG. The IDVG was calculated using a one-compartment model after intravenous administration of glucose (5 g) followed by serial arterial blood sampling. RESULTS: Although plasma glucose levels immediately before the second glucose challenge in either group were increased compared with those of the first challenge (P < 0.001, respectively), the bias of the IDVG measurements was 0.08 +/- 0.32 L (SD) for the 30-min group and -0.19 +/- 0.28 L for the 60-min group. CONCLUSIONS: Our results indicate that IDVG determinations can be reliably repeated within a minimum interval of 30 min.

Pool of dust particles over the Asian continent: balloon-borne optical particle counter and ground-based lidar measurements at Dunhuang, China.

Measurements of aerosols were made in 2001 and 2002 at Dunhuang (40 degrees 00'N, 94 degrees 30'E), China to understand the nature of atmospheric particles over the desert areas in the Asian continent. Balloon-borne measurements with an optical particle counter suggested that particle size and concentration had noticeable peaks in super micron size range not only in the boundary mixing layer but also in the free troposphere. Super-micron particle concentration largely decreased in the mid tropopause (from 5 to 10 km; above sea level, a.s.l.). Lidar measurements made during August 2002 at Dunhuang suggested the possibility that mixing of dust particles occurred from near the ground to about 6 km even under calm weather conditions, and a large depolarization ratio of particulate matter was found in the aerosol layer. The top of the aerosol layer was found at heights of nearly 6 km (a.s.l.). It is strongly suggested that nonspherical dust particles (Kosa particles) frequently diffused in the free atmosphere over the Taklamakan desert through small-scale turbulences and are possible sources of dust particles of weak Kosa events that have been identified in the free troposphere not only in spring but also in summer over Japanese archipelago. Electron microscopic experiments of the particles collected in the free troposphere confirmed that coarse and nonspherical particles observed by the mineral particle were major components of coarse mode (diameter larger than 1 microm) below about 5 km over Dunhuang, China.

Performance of bispectral index and auditory evoked potential monitors in detecting loss of consciousness during anaesthetic induction with propofol with and without fentanyl.

BACKGROUND AND OBJECTIVE: To investigate and compare the performance of bispectral index (BIS) and auditory evoked response index (AAI) in detecting the transition from consciousness to unconsciousness during anaesthesia induction by propofol, alone and in combination with fentanyl. METHODS: Anaesthesia was induced with either an intravenous infusion of 30 mg kg(-1)h(-1) of propofol plus 2 microg kg(-1) of fentanyl (Group PF, n = 20) or an intravenous infusion of 30 mg kg(-1) h(-1) of propofol plus normal saline (Group P, n = 20). BIS, AAI and the doses of propofol administered were recorded at the end-point of unresponsiveness to verbal commands. The propofol plasma concentration was also measured. RESULTS: The propofol dose and plasma propofol concentration required to achieve loss of consciousness were significantly lower in patients pretreated with fentanyl (P < 0.001). The mean BIS value at loss of consciousness was significantly different between the two groups (74.10 in Group PF vs. 60.80 in Group P) (P < 0.001). However, no difference in the AAI was seen between the two groups at loss of consciousness (32.90 in Group PF vs. 31.80 in Group P) (P > 0.05). In both groups, the regression analysis values (r-values) between BIS and plasma propofol concentrations at the onset of unconsciousness were higher than those between AAI and propofol concentrations (0.553 vs. 0.180 in Group P; 0.432 vs. 0.308 in Group PF). CONCLUSIONS: These results show that a fentanyl bolus is effective in augmenting the hypnotic effect of propofol during anaesthesia induction. AAI appears to be able to measure the transition from consciousness to unconsciousness at similar values, regardless of whether or not fentanyl pretreatment is used whereas the BIS values were not independent of fentanyl pretreatment. This suggests that AAI may be a better indicator of conscious status during propofol/fentanyl anaesthesia, where it appears to be independent of the anaesthesia regimen.

Orexinergic neurons and barbiturate anesthesia.

Orexins (OXs) regulate sleep with possible interactions with brain noradrenergic neurons. In addition, noradrenergic activity affects barbiturate anesthesia. As we have also recently reported that OXs selectively evoke norepinephrine release from rat cerebrocortical slices we hypothesized that barbiturate anesthesia may result from of an interaction with central orexinergic systems. To test this hypothesis, we performed a series of in vivo and in vitro studies in rats. In vivo, the effects of i.c.v. OX A, B and SB-334867-A (OX1 receptor antagonist) on pentobarbital, thiopental or phenobarbital-induced anesthesia times (loss of righting reflex) was assessed. In vitro effects of barbiturates and SB-334867-A on OX-evoked norepinephrine release from cerebrocortical slice was examined. In Chinese hamster ovary cells expressing human OX1/OX2 receptors OX A- and B-evoked increases in intracellular Ca2+ were measured with and without barbiturates. OX A and B significantly decreased pentobarbital, thiopental and phenobarbital anesthesia times by 15-40%. SB-334867-A increased thiopental-induced anesthesia time by approximately by 40%, and reversed the decrease produced by OX A. In vitro, all anesthetic barbiturates inhibited OX-evoked norepinephrine release with clinically relevant IC50 values. A GABAA antagonist, bicuculline, did not modify the inhibitory effects of thiopental and the GABAA agonist, muscimol, did not inhibit norepinephrine release. In addition there was no interaction of barbiturates with either OX1 or OX2 receptors. Collectively our data suggest that orexinergic neurons may be an important target for barbiturates, and GABAA, OX1 and OX2 receptors may not be involved in this interaction.

Effects of nicardipine and diltiazem on the bispectral index and 95% spectral edge frequency.

BACKGROUND AND OBJECTIVE: Previous studies have shown that L-type voltage-sensitive Ca2+ channel blocking agents increased and the L-type Ca2+ channel activator Bay K 8644 reduced the general anaesthetic potency in animals. As the bispectral index correlates with the depth of sedation, we examined whether L-type Ca2+ channel blocking agents affect the bispectral index. METHODS: Thirty hypertensive patients (systolic arterial pressure >160 mmHg) presenting for total intravenous anaesthesia with propofol, fentanyl and ketamine were recruited. Bispectral index monitoring was commenced directly the patients arrived in the operating theatre. All patients were given either nicardipine or diltiazem intravenously at the discretion of the anaesthesiologist in charge. RESULTS: Twenty-three and seven patients received nicardipine or diltiazem, respectively. The bispectral index level (mean (95% confidence interval)) did not change with either drug. In the nicardipine group, the bispectral index at 0, 5, 10 and 15 min was 55 (52-58), 55 (51-59), 55 (52-59) and 56 (53-59), respectively. In the diltiazem group, values were 59 (48-71), 60 (51-70), 61 (52-71) and 61 (50-72), respectively. Both L-type Ca2+ channel blocking agents significantly decreased arterial pressure. CONCLUSIONS: Clinical doses of nicardipine and diltiazem do not alter the bispectral index during general anaesthesia.

Effects of propofol on bronchoconstriction and bradycardia induced by vagal nerve stimulation.

BACKGROUND: Vagolysis has been considered as a mechanism by which propofol produces bronchodilation. However, it has also been suggested that propofol-induced bradycardia may result from increased vagal tone. In this study, we have determined whether propofol has vagolytic effects on both the airway and cardiovascular system. METHODS: Mongrel dogs were anesthetized with pentobarbital. Bronchoconstriction was assessed by measuring changes in a bronchial cross-sectional area (BCA) using a bronchoscopic method. Heart rate (HR) and direct arterial blood pressure were also monitored. Vagal nerve stimulation (VNS) was performed for 60 s to produce both bronchoconstriction and bradycardia. To determine the effect of propofol on VNS-induced bronchoconstriction and bradycardia (n = 7), 0 (saline), 2.0 and 20 mg/kg propofol were administered intravenously at 20-min intervals with VNS commenced 5 min later. In addition, to determine if propofol-induced bradycardia is due to a vagomimetic action, two groups of six dogs were given 20 mg/kg propofol with or without 0.2 mg/kg atropine pre-treatment. HR was measured before and 5 min after propofol. RESULTS: Propofol 20 mg/kg significantly inhibited VNS-induced bronchoconstriction. Although propofol per se significantly reduced HR (24%) and blood pressure (37%), the reduction in HR produced by VNS after 20 mg/kg propofol did not differ from that after saline or the lower dose of propofol (2 mg/kg). As atropine pre-treatment did not attenuate propofol-induced bradycardia, this response is unlikely to be simply due to vagomimetic actions. CONCLUSION: Propofol has vagolytic effects on the airway but does not worsen bradycardia produced by parasympathetic stimulation.

Differential effects of thiopental on methacholine- and serotonin-induced bronchoconstriction in dogs.

BACKGROUND: Thiopental sometimes causes bronchospasm during induction of anaesthesia. In addition, we have reported previously that thiopental produced transient bronchospasm, which was blocked by atropine pretreatment, and worsened histamine-induced bronchoconstriction in dogs. Previous in vitro reports suggest that synthesis of contractile cyclooxygenase products, such as thromboxane A(2), may be involved in the mechanism of bronchospasm. However, the in vivo spastic effects have not been defined comprehensively. METHODS: Twenty-seven mongrel dogs were anaesthetized with pentobarbital. Bronchoconstriction was elicited with methacholine (0.5 microg kg(-1)+5.0 microg kg(-1) min(-1); Mch group, n=7) or serotonin (10 microg kg(-1)+1 mg kg(-1) h(-1); 5HT group, n=20), and assessed as percentage changes in bronchial cross-sectional area (BCA, basal=100%) using a bronchoscope. In the 5HT group, dogs were subdivided into four groups of five each: S-5HT, I-5HT, 5HT-S and 5HT-A. In the S-5HT and I-5HT groups, 30 min before serotonin infusion dogs were given saline and indomethacin respectively at 5 mg kg(-1) i.v. In all groups, 30 min after bronchoconstrictor infusion started, dogs were given thiopental at doses between 0 (saline) and 20 mg kg(-1). In the 5HT-S and 5HT-A groups, dogs were given saline or atropine 0.2 mg kg(-1) i.v. 5 min after thiopental 20 mg kg(-1). RESULTS: Methacholine and serotonin reduced BCA by about 50 and 40% respectively. Thiopental 20 mg kg(-1) increased and decreased BCA by about 20 and 10% in the Mch and 5HT groups respectively. Indomethacin and atropine did not attenuate the potentiation of serotonin bronchoconstriction produced by thiopental. CONCLUSION: The present study indicates that thiopental may attenuate or worsen bronchoconstriction induced by muscarinic or serotonin receptor stimulation, respectively. The synthesis of contractile cyclooxygenase products and cholinergic stimulation may not be involved in the contractile effect of thiopental on serotonin bronchoconstriction.

Effects of three different L-type Ca2+ entry blockers on airway constriction induced by muscarinic receptor stimulation.

BACKGROUND: The crucial role of L-type Ca(2+) channels in airway smooth muscle contraction suggests that these channels could be an important therapeutic target. There are three separate drug binding sites on this channel: those for dihydropyridines, benzothiazepines and phenyl alkylamines. In this study, we examined the effects of the dihydropyridines nifedipine and nicardipine, the benzothiazepine diltiazem, and the phenylalkylamine verapamil on airway constriction. METHODS: Tension of guinea-pig tracheal strips was measured isometrically in vitro with a force displacement transducer. Strips were precontracted with carbachol 10(-7) M with or without 4-aminopyridine 10(-3) M, a voltage-sensitive K(+ )channel blocker. Then, nifedipine 10(-8)-10(-4) M, diltiazem 10(-8)-3 x 10(-4) M or verapamil 10(-8)-3 x 10(-4) M was added cumulatively to the organ bath (n=6 each). The bronchial cross-sectional area of pentobarbital-anaesthetized dogs was assessed using a bronchoscopy method. Bronchoconstriction was elicited with methacholine 0.5 micro g kg(-1) plus 5 micro g kg(-1) min(-1), and then nicardipine 0-1000 micro g kg(-1), diltiazem 0-3000 micro g kg(-1) or verapamil 0-3000 micro g kg(-1) were given i.v. (n=7 each). RESULTS: In the in vitro experiments, nifedipine and diltiazem fully reversed carbachol-mediated tracheal contraction with logIC(50) values of 4.76 (SEM 0.22) (mean 17.5 micro M) and 4.60 (0.33) (mean 24.8 micro M), respectively. Although verapamil 10(-6)-10(-4) M reversed the contraction by 87.2%, strip tension re-increased by 18.1% following maximal relaxation with verapamil 3 x 10(-4 )M. This re-increase was almost fully abolished by pretreatment with 4-aminopyridine. In the in vivo experiments, nicardipine and diltiazem dose-dependently reversed methacholine-induced bronchoconstriction, with logID(50) values of 3.22 (0.05) (mean 0.60 mg kg(-1)) and 1.85 (0.32) (mean 14.0 mg kg(-1)), respectively. Verapamil worsened methacholine-induced bronchoconstriction. CONCLUSIONS: Although supraclinical doses of dihydropyridines and benzothiazepines can produce airway relaxant effects, these agents are unlikely to be used in the treatment of bronchoconstriction. In addition, verapamil may aggravate airway constriction.

Flurbiprofen does not change the bispectral index and 95% spectral edge frequency during total intravenous anaesthesia with propofol and fentanyl.

BACKGROUND AND OBJECTIVE: Previous studies have shown that general anaesthetic agents modulate the production of hypothalamic prostaglandins (PG) D2 and E2, which are mediators of sleep and wakefulness respectively. Although flurbiprofen, a cyclo-oxygenase inhibitor, is used clinically as a non-steroidal anti-inflammatory agent and postoperative analgesic, it reduces prostaglandin production. Thus, this agent may affect the depth of sedation during general anaesthesia. In this study, we examined if flurbiprofen affects the bispectral index, which correlates with sedation levels. METHODS: Fifteen patients who underwent elective surgery under total intravenous anaesthesia with propofol and fentanyl were studied. The sedation level was monitored using a bispectral index monitor. On attainment of stable haemodynamics and a bispectral index, patients were given flurbiprofen axetil 50 mg intravenously. A bispectral index and 95% spectral edge frequency were recorded before and 5, 10, 15, 20 and 30 min after flurbiprofen axetil intravenously. RESULTS: Bispectral indexes of 51.7 (95% CI: 47.3-56.8), 51.7 (47.1-56.3), 51.3 (46.3-56.3), 50.3 (45.8-54.2), 48.9 (43.6-54.1) and 50.3 (45.5-55.2) at 0, 5, 10, 15, 20, 30 min after flurbiprofen axetil intravenously were observed. There was no change in this or 95% spectral edge frequency. CONCLUSIONS: Clinical dose of flurbiprofen axetil does not alter the bispectral index and 95% spectral edge frequency under total intravenous anaesthesia with propofol and fentanyl.

Ketamine and the inhibition of albumin extravasation in chemical peritonitis in rat.

BACKGROUND AND OBJECTIVE: It was previously reported that topical ketamine inhibits albumin extravasation in a rat chemical peritonitis model. Using the same model, the present study investigated whether intravenous ketamine inhibited this extravasation. METHODS: Twenty-four rats anaesthetized with pentobarbital (75 mg kg(-1)) were randomly assigned to two groups: ketamine and a 0.9% NaCl (saline) group (n = 12 each). Ketamine 1% or saline 0.1 mL kg(-1) min(-1) was given intravenously for 60 min to the respective group. After the abdomen had been opened, peritonitis was elicited by topically applying a filter paper containing 0.02 M HCl 0.07 mL onto the surface of the appendix or caecum for 5 min. Fifteen minutes after removal of the filter paper, Evans' blue dye (50 mg kg(-1)) was injected intravenously. The extravasated dye was colorimetrically quantified by a spectrophotometer at 620 nm. RESULTS: The infusion of ketamine significantly reduced Evans' blue extravasation: 5.26 (range 4.18-6.34) microg per 100 mg tissue compared with the saline group control: 6.81 (5.93-7.69) microg per 100 mg tissue (P < 0.05). CONCLUSIONS: It is suggested that ketamine anaesthesia may reduce albumin extravasation in inflammatory tissues.

Spasmolytic effects of colforsin daropate on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

BACKGROUND: We have previously found that agents increasing intracellular cAMP levels of smooth muscles, such as PDE3 inhibitors, aminophylline and prostaglandin E1, produce both bronchodilation and pulmonary vasodilation in serotonin-induced pulmonary hypertension and bronchoconstriction models. In the present study we have simultaneously evaluated the spasmolytic effects of colforsin daropate, a novel forskolin derivative, on serotonin-induced pulmonary hypertension and bronchoconstriction. METHODS: Ten mongrel dogs were anesthetized with pentobarbital. The pulmonary hypertension and bronchoconstriction were elicited with serotonin (10 microg/kg + 1 mg x kg(-1) x h(-1)) and assessed as percentage changes in pulmonary vascular resistance (PVR) and bronchial cross-sectional area (BCA) (basal = 100%). Initially, the relaxant effects of colforsin daropate (0-300 microg/kg) were determined. The PVR and BCA were assessed before and 30 min after serotonin infusion began and 5 min after each dose of colforsin daropate. To determine whether colforsin daropate-induced relaxation is independent of plasma catecholamine, propranolol 0.4 mg/kg was given following colforsin daropate 300 microg/kg i.v. RESULTS: Colforsin daropate reversed both pulmonary hypertension and bronchoconstriction dose-dependently: -logED50 (95% confidence intervals, mean ED50) for pulmonary hypertension and bronchoconstriction 5.44 (5.08-5.80, 3.6 microg/kg) and 4.90 (4.06-5.20, 12.5 microg/kg), respectively. However, colforsin daropate (>or= 30 microg/kg) produced a more pronounced systemic than pulmonary vasodilation. Although colforsin daropate (>or= 30 microg/kg) significantly increased plasma catecholamines, propranolol did not reverse the relaxant effects. CONCLUSIONS: Colforsin daropate may attenuate bronchoconstriction and pulmonary hypertension. In addition, as beta-blockade did not change the attenuation, the relaxant effects may be independent of plasma catecholamines.

Unventilated airway is time-dependently constricted in paralyzed dogs.

BACKGROUND: Apnea has been reported to produce bronchoconstriction and to cause hypoxia, hypercapnia, and modulation of vagal afferent nerves, which also change airway tone. In this study, the authors determined the mechanism of apnea-induced bronchoconstriction. METHODS: Twenty-eight dogs anesthetized and paralyzed were assigned to four groups (n = 7 each): apnea after artificial ventilation with 50% and 100% O2 groups (apnea-50% O2 and apnea-100% O2 groups, respectively), an apnea plus vagotomy group (fraction of inspired oxygen [FiO2] = 1.0), and a one-lung ventilation group (FiO2 = 1.0). The trachea was intubated with a single- or double-lumen tube in the three apnea groups or the one-lung ventilation group, respectively. The bronchial cross-sectional area (BCA) was assessed by the authors' bronchoscopic method. In the apnea-100% O2 and apnea plus vagotomy groups, a respirator was turned off for 5 min to produce apnea. In the apnea-50% O2 group, apnea was produced for 3 min. In the one-lung ventilation group, the right lumen was blocked for 5 min, and 15 min later, the left lumen was blocked for 5 min. BCA, arterial oxygen tension (PaO2), and arterial carbon dioxide tension (PaCO2) were assessed every minute. RESULTS: The BCA in intact dogs time-dependently decreased by approximately 20% and 40% at 3 and 5 min after apnea started, respectively, whereas they did not in vagotomized dogs. In the apnea-50% O2 and apnea-100% O2 groups, bronchoconstriction could occur without hypoxemia, although hypercapnia was observed in all dogs. In the one-lung ventilation group, despite the fact that PaCO2 increased by only 2 mmHg without hypoxemia, unventilated BCA time-dependently decreased by 33.6 +/- 10.3%, whereas ventilated BCA did not. CONCLUSION: The current study suggests that the unventilated airway may constrict spontaneously. In addition, the airway constriction could be vagally mediated but not due to hypoxia and hypercapnia.

Orexin A and B evoke noradrenaline release from rat cerebrocortical slices.

1. Orexin A and B, recently identified in the rat hypothalamus are endogenous neuropeptide agonists for the G-protein coupled orexin-1 (OX1) and orexin-2 (OX2) receptors. 2. In the present study, we have examined the effects of orexin A, B and raised extracellular K(+) on noradrenaline release from the rat cerebrocortical slice. We have compared this with other sleep-wake-related (excitatory) neurotransmitters; dopamine, glutamate, serotonin and histamine. 3. Neurotransmitter release studies were performed in rat cerebrocortical slices incubated in modified Krebs buffer (with and without Ca(2+)+EGTA 1 mM) with various concentrations of orexin A, B and K(+) for various times. 4. Orexin A and B-evoked (10(-7) M) noradrenaline release was time-dependent reaching a maximum some 10 min after stimulation. K(+) (40 mM) evoked release was also time dependent but reached a maximum after 6 min. Orexin A, B and K(+) stimulation of release was concentration dependent with pEC(50) and E(max) (% of basal) values of 8.74+/-0.32 (1.8 nM) and 263+/-14% and 8.61+/-0.38 (2.4 nM) and 173+/-7% and 1.43+/-0.02 (37 mM) and 1430+/-70%, respectively. Orexin-evoked release was partially extracellular Ca(2+) dependent. 5. Of the other transmitters studied there was a weak orexin A and B stimulation of glutamate release. In contrast K(+) evoked dopamine, glutamate, histamine and serotonin release with pEC(50) and E(max) (% of basal) values of 1.47+/-0.05 (34 mM) and 3430+/-410%, 1.38+/-0.04 (42 mM) and 1240+/-50%, 1.47+/-0.02 (34 mM) and 480+/-10% and 1.40+/-0.05 (40 mM) and 560+/-60% respectively. 6. We conclude that the neuropeptides orexin A and B evoke noradrenaline release from rat cerebrocortical slices.