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We examined the relationships between recall of dreaming during anesthesia and postoperative nausea and vomiting (PONV). We found a relationship between PONV within 24 h and age <50 years, use of postoperative epidural analgesia with morphine, and female gender. We also found a relationship between PONV lasting more than 24 h and dream recall. As serotonin plays an important role for both inducing PONV and dream recall, results of the present study may suggest a possible relationship between dream recall and PONV.

Background: Emergency surgery itself induces high risk for postoperative mortality and morbidities; however, it remains unknown which concomitant pathological conditions of emergency surgeries are causative factors of deteriorating outcomes. This study examined the causal factors of postoperative mortality and morbidity in cases of emergency surgery., Methods: Patients undergoing emergency surgery from January to December 2007 were enrolled in this retrospective cohort study. Causal relationships were analyzed by stepwise multivariate logistic regression analysis between possible independent factors (sex, age, kind of surgical department, timing of surgery, duration of surgery, blood transfusion, deteriorated consciousness level, shock state, abnormal coagulate state, and history of hypertension, diabetes, ischemic heart disease, chronic obstructive pulmonary disease, renal failure, and anemia) and postoperative mortality or morbidities (failure of removal of tracheal tube after operation, tracheotomy, cerebral infarction, massive hemorrhage, severe hypotension, severe hypoxemia, and severe arrhythmia during or after surgery)., Results: Shock, deteriorated consciousness level, chronic obstructive lung disease, and ischemic heart disease were significant risk factors for mortality (OR 14.2, 7.9, 6.4, and 3.8, respectively), and deteriorated consciousness level, blood transfusion, shock, chronic obstructive lung disease, diabetes, cardiovascular surgery, and operation longer than 2 h were significant risk factors for morbidity (OR 19.1, 3.3, 3.0, 2.5, 2.4, 2.4, and 1.8, respectively)., Conclusion: State of shock, deteriorated consciousness level, chronic obstructive lung disease, ischemic heart disease, hemorrhage requiring blood transfusion, age over 80 years, cardiovascular surgery, surgeries at night, and surgeries of duration more than 2 h cause patients to be strongly susceptible to postoperative mortality or morbidity in emergency surgeries.

Objective: This study examined the hypothesis that ipsilateral upper extremity elevation for muscle-sparing thoracotomy procedures contributes to the postoperative shoulder pain., Design: Prospective observational study., Setting: Medical center., Participants: ASA physical status 1-2 patients undergoing elective lung surgeries including pneumonectomy, lobectomy, and segmentectomy performed through either the anterolateral approach or video-assisted thoracotomy surgery., Interventions: Postoperative observation of ipsilateral shoulder pain., Measurements and Main Results: Postoperative examinations of sites of shoulder pain (clavicle, anterior, lateral,or posterior aspect of acromion, posterior neck, supraspinatus, infraspinatus, and these entire areas) with or without trigger points, visual analog scale score of wound pain, and requested counts of analgesics. The number of patients who suffered from postoperative shoulder pain was 37 of 70 (52.9%). Demographic data, anterolateral/VATS ratio, VAS scores, and requested counts of rescue analgesics requirement were similar in the groups of patients with and without postoperative shoulder pain. The segmentectomy caused a significantly higher incidence of postoperative shoulder pain compared with other procedures (p < 0.05). The supra- and infraspinatus were significantly higher areas of painful regions compared to the other sites. The 16 of 37 patients (43.2%) with shoulder pain showed defined trigger points in their painful areas., Conclusion: These results supported the hypothesis that myofascial involvement contributed, to some extent, to shoulder pain after muscle-sparing thoracotomy with ipsilateral upper extremity elevation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Adenosine triphosphate (ATP)-sensitive K(+) channels contribute to significant regulatory mechanisms related to organ blood flow in both physiological and pathological conditions. High glucose impairs arterial ATP-sensitive K(+) channel activity via superoxide production. However, the effects of anesthetics on this pathological process have not been evaluated in humans. In the present study, we investigated whether pretreatment with the volatile anesthetic isoflurane preserves ATP-sensitive K(+) channel activity in the human artery exposed to oxidative stress caused by high glucose., Methods: All experiments were performed using human omental arteries without endothelium in the presence of d-glucose (5.5 mmol/L). Some arteries were treated with isoflurane (1.15% or 2.3%) in combination with d- or l-glucose (20 mmol/L) for 60 minutes, and then only isoflurane was discontinued. Relaxation and hyperpolarization of arterial segments in response to an ATP-sensitive K(+) channel opener levcromakalim were evaluated using the isometric force recording or electrophysiological study, respectively. Superoxide production was determined by dihydroethidium fluorescence. Immunohistochemical analysis for a subunit of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p47phox was performed. Data were evaluated using repeated-measures analysis of variance or a factorial analysis of variance as appropriate, followed by Scheffé test., Results: The ATP-sensitive K(+) channel antagonist glibenclamide (10(-6) mol/L) abolished relaxation induced by cumulative addition of levcromakalim (10(-8) to 10(-5) mol/L) in arteries treated with l-glucose (20 mmol/L). Incubation with d-glucose (20 mmol/L) impaired the vasorelaxation induced by levcromakalim. The selective NADPH oxidase NOX2 inhibitor gp91ds-tat (10(-6) mol/L) and pretreatment with isoflurane (1.15% and 2.3%) restored relaxation in response to levcromakalim in arteries treated with d-glucose (20 mmol/L). Isoflurane (2.3%), gp91ds-tat (10(-6) mol/L), and their combination similarly restored hyperpolarization in response to levcromakalim (3 × 10(-6) mol/L) in arteries treated with d-glucose (20 mmol/L). Along with these results, isoflurane (2.3%) reduced superoxide production and the intracellular mobilization of the cytosolic NOX2 subunit p47phox toward smooth muscle cell membrane in arteries treated with d-glucose (20 mmol/L)., Conclusions: We have demonstrated for the first time a beneficial effect from the pretreatment with isoflurane on the isolated human artery. Pretreatment with isoflurane preserves ATP-sensitive K(+) channel activity in the human omental artery exposed to oxidative stress induced by high glucose, whereas the effect seems to be mediated by NADPH oxidase inhibition. Volatile anesthetics may protect human visceral arteries from malfunction caused by oxidative stress.

Background: We sought to determine the effect of remifentanil on sinus node function and the atrial-His (AH) interval in pediatric patients undergoing radiofrequency catheter ablation., Methods: Sixty pediatric patients with Wolff-Parkinson-White syndrome were prospectively enrolled in this study. General anesthesia was induced and maintained with a continuous infusion of propofol. We recorded the calculated sinoatrial conduction time (CSACT), corrected sinus node recovery time (CSNRT), and AH interval when the patients were in a stable anesthetic state and compared the values before and during remifentanil administration at a moderate dose (0.2 μg · kg(-1) · min(-1)) or a high dose (0.4 μg · kg(-1) · min(-1)). Data are expressed as mean (95% confidence interval)., Results: At the moderate dose, remifentanil prolonged CSNRT (from 177 [117-237] milliseconds to 245 [167-322] milliseconds after administration; P=0.016), but had no effect on either CSACT (P=0.59) or AH interval (P=0.11). However, high-dose remifentanil prolonged both CSNRT (from 201 [144-260] milliseconds to 307 [232-382] milliseconds after administration; P=0.019) and CSACT (from 48 [31-65] milliseconds to 78 [59-96] milliseconds after administration; P=0.038), but had no effect on the AH interval (P=0.058). The interaction in CSNRT between remifentanil administration and its dose was not different (P=0.44)., Conclusion: Remifentanil may inhibit both intraatrial conduction and sinus node automaticity, but it has no effect on conduction through the atrioventricular node. Dose dependency was not observed within the range of 0.2 to 0.4 μg · kg(-1) · min(-1) of remifentanil., (© 2011 International Anesthesia Research Society)

Methemoglobinemia is a fatal complication of local anesthesia. We describe a case report of female neonate who developed severe methemoglobinemia after extraction of neonatal teeth conducted with general anesthesia plus local injection of Citanest-Octapressin(®) (propitocaine of approximately 10 mg/kg). Central cyanosis appeared within an hour after surgery. The percentage of methemoglobin reached up to 43.9%. Not only pediatric dentists but also anesthesiologists generally agree with the idea that local anesthesia provides various benefits in painful procedures in neonates. However, this case may serve as a warning when using Citanest-Octapressin(®), which is still commercially available for neonatal patients.

Background: In some types of pediatric supraventricular tachycardia, reentrant mechanisms are sensitive to enhanced vagal tone. Propofol is a feasible anesthetic for pediatric electrophysiological study and radiofrequency catheter ablation. Although fentanyl and propofol infusions both enhance cardiac vagal tone, it is unclear whether the combination of propofol and fentanyl has a potential to enhance it. In this study, we evaluated the hypothesis that fentanyl combined with propofol could alter cardiac electrophysiological activities in pediatric patients undergoing electrophysiological study and radiofrequency catheter ablation., Methods: Twenty-seven pediatric patients (9 Wolff-Parkinson-White syndrome, 7 concealed accessory pathway and 11 atrioventricular nodal reentry tachycardia) were enrolled in this study. Anesthesia was induced with propofol 2.0 mg/kg and was maintained with a continuous infusion of propofol at a rate of 100-167 microg x kg(-1) x min(-1). During a stable anesthetic state, the calculated sinoatrial conduction time and corrected sinus node recovery time (CSNRT) were measured before and after fentanyl administration. The fentanyl dose consisted of an initial 2.0 microg/kg IV bolus and subsequent continuous infusion of 0.075 microg x kg(-1) x min(-1)., Results: Bispectral Index scores and systemic blood pressure remained unchanged throughout the examinations. Fentanyl administration significantly prolonged CSNRT (P = 0.005) but not calculated sinoatrial conduction time (P = 0.35)., Conclusion: Since an enhanced cardiac vagal tone is one of the causative factors for prolonged CSNRT, our findings greatly support the hypothesis that fentanyl combined with propofol has a potential to enhance cardiac vagal tone.

The present study was designed to examine roles of the phosphatidylinositol 3-kinase-Akt pathway and reduced nicotinamide-adenine dinucleotide phosphate oxidases in the reduced ATP-sensitive K(+) channel function via superoxide produced by high glucose in the human artery. We evaluated the activity of the phosphatidylinositol 3-kinase-Akt pathway, as well as reduced nicotinamide-adenine dinucleotide phosphate oxidases, the intracellular levels of superoxide and ATP-sensitive K(+) channel function in the human omental artery without endothelium. Levels of the p85-alpha subunit and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits, including p47phox, p22phox, and Rac-1, increased in the membrane fraction from arteries treated with D-glucose (20 mmol/L) accompanied by increased intracellular superoxide production. High glucose simultaneously augmented Akt phosphorylation at Ser 473, as well as Thr 308 in the human vascular smooth muscle cells. A phosphatidylinositol 3-kinase inhibitor LY294002, as well as tiron and apocynin, restored vasorelaxation and hyperpolarization in response to an ATP-sensitive K(+) channel opener levcromakalim. Therefore, it can be concluded that the activation of the phosphatidylinositol 3-kinase-Akt pathway, in combination with the translocation of p47phox, p22phox, and Rac-1, contributes to the superoxide production induced by high glucose, resulting in the impairment of ATP-sensitive K(+) channel function in the human visceral artery.

Background: C-reactive protein is a crucial risk factor for cardiovascular diseases. Previous studies demonstrated that in patients with obstructive sleep apnea syndrome (OSAS), levels of this protein elevate dependently on the degree of upper airway obstruction. However, it has not been determined whether the surgery for OSAS reduces the levels of C-reactive protein by restoring the airway opening. Therefore, we evaluated the effect of uvulopalatopharyngoplasty (UPPP) on levels of serum C-reactive protein in patients with this syndrome., Methods: Fifteen adult patients with mild to severe OSAS were enrolled in this study. Levels of serum C-reactive protein and sleep parameters including apnea-hypopnea index a month before and 3 months after UPPP were evaluated using peripheral venous blood and polysomnography, respectively., Results: Uvulopalatopharyngoplasty significantly restored sleep parameters, accompanying with decreased levels of C-reactive protein (from 0.21 +/- 0.17 to 0.10 +/- 0.16 mg/dL, P < .05)., Conclusions: In patients with OSAS, UPPP appears to decrease levels of serum C-reactive protein. Surgical therapy may reduce inflammatory response in these patients.

The present study was designed to examine whether in the human artery, synthetic peroxisome proliferator-activated receptor (PPAR)-gamma agonists restore vasorelaxation as well as hyperpolarization via ATP-sensitive K+ channels impaired by the high concentration of D-glucose and whether the restoration may be mediated by the antioxidant capacity of these agents. The isometric force and membrane potential of human omental arteries without endothelium were recorded. The production rate of superoxide was evaluated using a superoxide-generating system with xanthine-xanthine oxidase in the absence of smooth muscle cells. Glibenclamide abolished vasorelaxation and hyperpolarization in response to levcromakalim. Addition of D-glucose (20 mM) but not L-glucose (20 mM) reduced this vasorelaxation and hyperpolarization. Synthetic PPAR-gamma agonists (troglitazone and rosiglitazone) and/or an inhibitor of superoxide generation (4,5-dihydroxy-1,3-benzene-disulfonic acid, Tiron), but not a PPAR-alpha agonist (fenofibrate), restored vasorelaxation and hyperpolarization in response to levcromakalim in arteries treated with D-glucose. Troglitazone and rosiglitazone, but not fenofibrate, decreased the production rate of superoxide without affecting uric acid generation. These findings suggest that synthetic PPAR-gamma agonists recover the function of ATP-sensitive K+ channels reduced by the high concentration of glucose in human vascular smooth muscle cells and that the effect of these agonists may be mediated in part by their antioxidant capacity.

Purpose: Beta-adrenergic receptor antagonists (beta-antagonists) have long been used to control perioperative tachyarrhythmias. The effects of a beta(1)-antagonist, landiolol, on perioperative hemodynamics are unknown. We aimed to determine the appropriate dosage of landiolol for the treatment of hemodynamic changes in response to endotracheal intubation., Methods: Sixty-four patients without heart disease or hypertension, were assigned to receive saline (group C) or landiolol (0.1 or 0.3 mg.kg(-1); groups L1 and L3). Anesthesia was induced with propofol (2 mg.kg(-1) iv) followed by saline or landiolol iv. After ventilation with facemask using 2% sevoflurane in 100% oxygen for 90 sec, endotracheal intubation was performed. After intubation, anesthesia was maintained using 1% sevoflurane in combination with 50% nitrous oxide. Values of heart rate and mean arterial blood pressure were recorded before induction to five minutes after intubation., Results: In group C, heart rate and mean blood pressure increased simultaneously after tracheal intubation, compared with baseline values. Heart rate values were attenuated immediately before as well as after intubation in group L3, compared with groups C and L1. Heart rate did not increase after tracheal intubation in group L1, compared with baseline. In contrast, mean arterial blood pressure values did not differ among groups., Conclusions: The newly developed beta(1)-antagonist landiolol (0.1 and 0.3 mg.kg(-1)) may help prevent tachycardia without affecting blood pressure during the induction of anesthesia.

Objective: The present study was designed to examine in the human omental artery whether high concentrations of D-glucose inhibit the activity of ATP-sensitive K+ channels in the vascular smooth muscle and whether this inhibitory effect is mediated by the production of superoxide., Methods and Results: Human omental arteries without endothelium were suspended for isometric force recording. Changes in membrane potentials were recorded and production of superoxide was evaluated. Glibenclamide abolished vasorelaxation and hyperpolarization in response to levcromakalim. D-glucose (10 to 20 mmol/L) but not l-glucose (20 mmol/L) reduced these vasorelaxation and hyperpolarization. Tiron and diphenyleneiodonium, but not catalase, restored vasorelaxation and hyperpolarization in response to levcromakalim in arteries treated with D-glucose. Calphostin C and Gö6976 simultaneously recovered these vasorelaxation and hyperpolarization in arteries treated with D-glucose. Phorbol 12-myristate 13 acetate (PMA) inhibited the vasorelaxation and hyperpolarization, which are recovered by calphostin C as well as Gö6976. D-glucose and PMA, but not l-glucose, significantly increased superoxide production from the arteries, whereas such increased production was reversed by Tiron., Conclusions: These results suggest that in the human visceral artery, acute hyperglycemia modulates vasodilation mediated by ATP-sensitive K+ channels via the production of superoxide possibly mediated by the activation of protein kinase C.

Background: Carbon dioxide is an important vasodilator of cerebral blood vessels. Cerebral vasodilation mediated by adenosine triphosphate (ATP)-sensitive K+ channels has not been demonstrated in precapillary microvessel levels. Therefore, the current study was designed to examine whether ATP-sensitive K+ channels play a role in vasodilation induced by mild hypercapnia in precapillary arterioles of the rat cerebral cortex., Methods: Brain slices from rat cerebral cortex were prepared and superfused with artificial cerebrospinal fluid, including normal (Pco2 = 40 mmHg; pH = 7.4), hypercapnic (Pco2 = 50 mmHg; pH = 7.3), and hypercapnic normal pH (Pco2 = 50 mmHg; pH = 7.4) solutions. The ID of a cerebral parenchymal arteriole (5-9.5 microm) was monitored using computerized videomicroscopy., Results: During contraction to prostaglandin F2alpha (5 x 10(-7) m), hypercapnia, but not hypercapnia under normal pH, induced marked vasodilation, which was completely abolished by the selective ATP-sensitive K+ channel antagonist glibenclamide (5 x 10(-6) m). However, the selective Ca2+-dependent K+ channel antagonist iberiotoxin (10(-7) m) as well as the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (10(-4) m) did not alter vasodilation. A selective ATP-sensitive K+ channel opener, levcromakalim (3 x 10(-8) to 3 x 10(-7) m), induced vasodilation, whereas this vasodilation was abolished by glibenclamide., Conclusion: These results suggest that in parenchymal microvessels of the rat cerebral cortex, decreased pH corresponding with hypercapnia, but not hypercapnia itself, contributes to cerebral vasodilation produced by carbon dioxide and that ATP-sensitive K+ channels play a major role in vasodilator responses produced by mild hypercapnia.

Unlabelled: Cerebral microemboli can occur during arthroplasty with the use of bone cement. Astroglial S-100B protein is a sensitive marker of cerebral damage. Therefore, we designed this study to determine the effect of bone cement on the brain by investigating serum levels of S-100B protein in patients undergoing bone surgery with or without bone cement. Fourteen patients undergoing knee arthroplasty (n = 7) or reamed intramedullary nailing for tibial fracture (n = 7) requiring a pneumatic tourniquet were enrolled in this study. Bone cement containing polymethyl methacrylate and methyl methacrylate was used for every patient undergoing knee arthroplasty. Serum samples were obtained from venous blood before the induction of general anesthesia, 15 min after deflation of a pneumatic tourniquet, and 3 days after the operation. The serum level of S-100B protein was significantly increased 15 min after a pneumatic tourniquet deflation in the knee arthroplasty group compared with the tibial fracture group (0.41 and 0.08 ng/mL, respectively; P < 0.05). In all patients studied, no neurological abnormalities were noted in the postoperative period. These results suggest that, in patients undergoing knee arthroplasty, bone cement may transiently induce astroglial injury, although it does not alter neurological outcome., Implications: Serum S-100B protein was significantly increased 15 min after a pneumatic tourniquet deflation in patients undergoing knee arthroplasty with bone cement, but not in those undergoing reamed intramedullary nailing for tibial fracture without bone cement. These results suggest that bone cement may transiently induce astroglial injury.

Unlabelled: Hypoxia induces vasodilation, partly via the activation of K(+) channels. Lidocaine impairs vasorelaxation mediated by a K(+) channel opener, suggesting that this antiarrhythmic drug may inhibit hypoxia-induced vasodilation mediated by K(+) channels. We designed the current study to determine whether, in the carotid artery, K(+) channels contribute to vasorelaxation in response to hypoxia and whether lidocaine modulates vasorelaxation induced by K(+) channels via pathophysiological and pharmacological stimuli. Rings of rat common carotid artery without endothelium were suspended for isometric force recording. During contraction to phenylephrine, hypoxia-induced vasorelaxation or concentration-response to an adenosine triphosphate-sensitive K(+) channel opener was obtained changing control gas to hypoxic gas and the cumulative addition of levcromakalim, respectively. Hypoxia-induced vasorelaxation was significantly reduced by glibenclamide (5 micro M) but not by iberiotoxin (0.1 micro M), apamin (0.1 micro M), BaCl(2) (10 micro M), or 4-aminopyridine (1 mM). Levcromakalim-induced vasorelaxation was completely abolished by glibenclamide. Lidocaine (10-100 micro M) concentration-dependently inhibited this vasodilation, whereas it did not affect hypoxia-induced vasodilation. These results suggest that adenosine triphosphate-sensitive K(+) channels play a role in hypoxia-induced vasodilation in the rat carotid artery and that lidocaine differentially modulates vasodilation via these channels activated by pathophysiological and pharmacological stimuli., Implications: In rat carotid artery, levcromakalim produced vasorelaxation mediated by adenosine triphosphate (ATP)-sensitive K(+) channels, whereas hypoxia induced it partly via these channels. Lidocaine inhibited vasorelaxation induced by an ATP-sensitive K(+) channel opener but not by hypoxia, indicating the differential mechanisms of modulatory effects of this antiarrhythmic drug on vasodilation via ATP-sensitive K(+) channels activated by pathophysiological and pharmacological stimuli.

Unlabelled: The modification of vasodilation through adenosine triphosphate (ATP)-sensitive K(+) channels induced by antiarrhythmic drugs has not been studied in chronic hypertension. We designed the present study to examine whether mexiletine modulates vasorelaxation via these channels in hypertensive rat aortas. Normotensive and hypertensive rat aortas without endothelium were suspended for isometric force recording. Mexiletine (3 x 10(-5) M) increased vasorelaxation induced by levcromakalim (10(-8)-10(-5) M) in normotensive, but not hypertensive, rat aortas. Mexiletine (10(-5) to 3 x 10(-5) M) also augmented vasorelaxation to sodium nitroprusside (10(-10)-10(-5) M) only in normotensive rat aortas, whereas mexiletine (3 x 10(-5) M) did not affect this vasodilation in aortas treated with an ATP-sensitive K(+) channel antagonist glibenclamide (10(-5) M). A nitric oxide scavenger (carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide; 10(-3) M) abolished augmented vasorelaxation to sodium nitroprusside induced by mexiletine (3 x 10(-5) M) in normotensive rat aortas, whereas a soluble guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo [4,3,-a]quinoxaline-1-one; 10(-5) M) failed to alter this augmentation of vasorelaxation. These results suggest that mexiletine induces augmentation of vasodilation via ATP-sensitive K(+) channels activated by the opener as well as a nitric oxide donor only in normotensive rat aortas. The vasodilator effects of mexiletine are partly caused by the soluble guanylate cyclase-independent action of nitric oxide on these channels., Implications: Mexiletine induces augmentation of vasodilation mediated by adenosine triphosphate (ATP)-sensitive K(+) channels activated by the opener as well as a nitric oxide donor in normotensive, but not hypertensive, rat aortas, partly by the soluble guanylate cyclase-independent action of nitric oxide on ATP-sensitive K(+) channels of vascular smooth muscle cells.

Purpose: The present study was designed to examine the effects of halothane and isoflurane on acetylcholine-induced, endothelium-dependent vasodilation in rat mesenteric arterial beds perfused at a constant flow both in vitro and in situ., Methods: In the in-vitro preparation, the mesenteric artery was cannulated and perfused (5 ml x min(-1)). The perfusion pressure was continuously monitored. Under active tone induced by methoxamine, the effects of halothane and isoflurane on the vasodilator response to acetylcholine in either the presence or absence of NG-nitro-L-arginine (L-NA), tetraethylammonium (TEA), or KCl (30 mM)-depolarization were examined. All experiments in these preparations were performed in the presence of indomethacin (10 mM). In the in-situ experimental model, rats were anesthetized with pentobarbital and the lungs were mechanically ventilated via a tracheostomy with a ventilator. The superior mesenteric artery was cannulated and used for the monitoring of the perfusion pressure. Blood shunting with constant flow (2 ml x min(-1)) from the carotid artery to the superior mesenteric artery was introduced with clamping at the immediately distal portion of the mesenteric artery branching. Following 20-min ventilation with halothane or isoflurane at 1 minimum alveolar concentration (MAC) in oxygen, acetylcholine was given from the mesenteric artery, under active tone induced by norepinephrine (100 mg x kg(-1) x hr(-1))., Results: In the in-vitro preparation, the nitric oxide synthase inhibitor, L-NA (100 microM) did not affect vasodilations to acetylcholine (1, 10 nM), while the K+ channel inhibitor TEA (10 mM), as well as KCl (30 mM), significantly reduced these vasodilations. However, only in the presence of L-NA, TEA and KCl completely abolished the vasodilations produced by acetylcholine. The higher concentrations of halothane (2.0%, 3.0%), but neither isoflurane (3.0%) nor the lower concentration of halothane (1.0%), significantly impaired vasodilator responses to acetylcholine in the presence of L-NA, whereas the volatile anesthetics did not affect these vasodilations in the absence of L-NA. Halothane (2.0%) did not alter the vasodilation produced by acetylcholine in the presence of TEA or KCl. In the in-vivo preparation, the vasodilator effects of acetylcholine (1 and 10 nmol) were not affected by the inhalation of halothane (1.0%) or isoflurane (1.3%)., Conclusion: These results suggest that, in resistance arteries in conditions of constant flow, halothane and isoflurane do not affect vasodilations in response to an endothelium-dependent agonist. However, in these preparations, once the enzymatic activity of nitric oxide synthase is inhibited, higher concentrations of halothane, but neither isoflurane nor the lower concentration of halothane, appear to impair endothelium-dependent relaxations, probably mediated by TEA-sensitive K+ channels.

Background: The effect of ketamine on vasodilation mediated by adenosine triphosphate (ATP)-sensitive K(+) channels has not been studied. The present study was designed to determine whether ketamine might stereoselectively affect vasorelaxation induced by an ATP-sensitive K(+) channel opener in the isolated rat aorta., Methods: Rings of the rat aorta with or without endothelium were suspended for isometric force recording. During contraction to phenylephrine (3 x 10(-7) M), vasorelaxation in response to an ATP-sensitive K(+) channel opener levcromakalim (10(-8) to 10(-5) M) or a nitric oxide donor sodium nitroprusside (10(-10) to 10(-5) M) was obtained. Glibenclamide (10(-5) M), S(+) ketamine (10(-4) M), or ketamine racemate (10(-5) to 10(-4) M) was applied 15 min before addition of phenylephrine., Results: Vasorelaxation induced by levcromakalim was completely abolished by an ATP-sensitive K(+) channel antagonist glibenclamide (10(-5) M) in the aorta with or without endothelium. Ketamine racemate (3 x 10(-5) to 10(-4) M) significantly inhibited this vasorelaxation in a concentration-dependent fashion, whereas S(+) ketamine did not affect the relaxation. However, the highest concentration of ketamine racemate and S(+) ketamine used in the present study did not alter vasorelaxation in response to sodium nitroprusside in the aorta without endothelium., Conclusion: In the isolated rat aorta, clinically relevant concentrations of ketamine racemate can inhibit relaxation induced by an ATP-sensitive K(+) channel opener, whereas S(+) ketamine did not produce any inhibitory effect on this vasorelaxation. These results suggest that ketamine stereoselectively alters vasodilation ATP-sensitive K(+) channels in the conduit artery.

Unlabelled: Studies in cardiac myocytes have shown that cibenzoline reduces adenosine triphosphate (ATP)-sensitive K(+) currents, suggesting that this class Ia antiarrhythmic drug may modify the activity of ATP-sensitive K(+) channels in these preparations. The effects of class Ia antiarrhythmic drugs on vasodilation mediated by ion channels have not been studied. Therefore, we designed this study to examine whether cibenzoline may produce changes in vasorelaxation in response to a selective ATP-sensitive K(+) channel opener, levcromakalim, in the isolated rat carotid artery. Rings of rat carotid arteries without endothelium were suspended for isometric force recording. Concentration-response curves were obtained in a cumulative fashion. During submaximal contraction to phenylephrine (3 x 10(-7) M), vasorelaxation in response to levcromakalim (10(-8) to 10(-5) M) or 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7; 10(-10) to 10(-5) M) was obtained. During contraction to phenylephrine, levcromakalim induced concentration-dependent vasorelaxation. A selective ATP-sensitive K(+) channel antagonist, glibenclamide (5 x 10(-6) M), completely abolished vasorelaxation in response to levcromakalim, whereas a selective Ca(2+)-dependent K(+) channel antagonist, iberiotoxin (5 x 10(-8) M), did not affect the relaxation. Cibenzoline (10(-6) to 10(-5) M) significantly reduced vasorelaxation to levcromakalim in a concentration-dependent fashion. In contrast, cibenzoline (10(-5) M) did not alter vasorelaxation to a nitric oxide donor, NOC-7. These results suggest that from the clinically relevant concentrations, a novel class Ia antiarrhythmic drug, cibenzoline, impairs carotid vasodilation mediated by ATP-sensitive K(+) channels., Implications: In isolated rat carotid artery, cibenzoline (10(-6) to 10(-5) M) reduced vasorelaxation to levcromakalim in a concentration-dependent fashion. These results suggest that from the clinically relevant concentrations, a novel class Ia antiarrhythmic drug, cibenzoline, impairs carotid vasodilation mediated by adenosine triphosphate-sensitive K(+) channels.

Hydrogen peroxide and peroxynitrite induce relaxations via ATP-sensitive K+ channels, indicating that oxygen-derived free radicals may activate these channels. Levels of free radicals are increased throughout the arterial wall in animal models of atherosclerosis, and therefore, vasorelaxation via ATP-sensitive K+ channels may be augmented in chronic hypertension. The present study was designed to determine whether relaxations to an ATP-sensitive K+ channel opener, levcromakalim, are increased in the aorta from spontaneously hypertensive rats (SHR) and whether free radical scavengers reduce these relaxations. Rings of aortas without endothelium taken from age-matched Wistar-Kyoto rats (WKY) and SHR were suspended for isometric force recording. Relaxations to levcromakalim (10(-8) to 10(-5) M), which are abolished by glibenclamide (10(-5) M), were augmented in the aorta from SHR, compared to those in the aorta from WKY. In the aorta from SHR, catalase (1200 U/ml), but neither superoxide dismutase (150 U/ml) nor deferoxamine (10(-4) M), reduced relaxations to levcromakalim, whereas in the aorta from WKY, the free radical scavengers did not affect these relaxations. These results suggest that in chronic hypertension, vasorelaxation to an ATP-sensitive K+ channel opener is augmented and that hydrogen peroxide produced in smooth muscle cells may partly contribute to these relaxations.

The present study was designed to examine the role of basally released nitric oxide in relaxations to an ATP-sensitive K+ channel opener. Whether relaxations to levcromakalim are modulated by endothelial removal or the inhibitors of vasodilator effects of endothelium-derived nitric oxide, were investigated in the rat aorta. During contractions to phenylephrine (3 x 10(-7) to 10(-6) M), levcromakalim (10(-8) to 10(-5) M) or a nitric oxide donor, 1-hydroxy-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7, 10(-9) to 10(-5) M), was added in a cumulative fashion. Relaxations to levcromakalim (10(-8) to 10(-5) M) were significantly reduced by the endothelium-removal. In aortas with endothelium, relaxations in response to levcromakalim were decreased by selective inhibitors of nitric oxide synthase (N(G)-nitro-L-arginine methyl ester, 10(-4) M) and soluble guanylate cyclase (1H-[1,2,4]oxadiazolo[4,3-a]quinoxaline-1-one; ODQ, 10(-5) M) and a scavenger of nitric oxide (carboxy-PTIO, 10(-3) M). Relaxations to levcromakalim in aortas treated with these inhibitors are comparable to those seen in aortas without endothelium. KCl (30 mM) and an ATP-sensitive K+ channel inhibitor, glibenclamide (10(-5) M), abolished relaxations to levcromakalim in aortas with or without endothelium, whereas glibenclamide did not alter relaxations to NOC-7 (10(-9) to 10(-5) M) in aortas without endothelium. These results suggest that in rat aortas, inhibition of vasodilator effects of basally released nitric oxide can reduce relaxations via ATP-sensitive K+ channels, although these channels do not mediate relaxations to exogenously applied nitric oxide.

Unlabelled: Stimulation of nonadrenergic noncholinergic (NANC) nerves elicits relaxation of canine cerebral arteries via the nitric oxide (NO)-cGMP pathway. The purpose of this study was to investigate the effects of halothane and isoflurane on the relaxant response of isolated canine cerebral arteries to NANC nerve stimulation. The isometric tension of isolated canine cerebral arteries, which had been denuded of endothelium, was measured in a tissue bath. The application of transmural electrical stimulation (TES) at a frequency of 5 Hz elicited a transient relaxation of arteries partially contracted with prostaglandin F2alpha. This effect was abolished by treatment with N(G)-nitro-L-arginine (3 x 10[-5] M), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10[-5] M), or tetrodotoxin (10[-6] M). Treatment with halothane (2.3%) or isoflurane (2.3% and 3.5%) attenuated the relaxant response to TES (P < 0.05). Halothane (2.3%) but not isoflurane (2.3% and 3.5%) attenuated relaxation induced by s-nitro-N-acetylpenicillamine. We suggest that halothane and isoflurane inhibit cerebroarterial vasodilation mediated via NO-cGMP pathway activated by stimulation of the NANC nerves. The sites of action of halothane and isoflurane on the NO-cGMP pathway may differ., Implications: Nonadrenergic noncholinergic nerves play a role in the regulation of vascular tone in cerebral arteries via the nitric oxide-cGMP pathway. This study showed that, in isolated canine cerebral arteries, halothane and isoflurane inhibit the relaxation caused by nonadrenergic noncholinergic nerve stimulation, but their sites of action may differ.

Purpose: The effect of halothane was compared on acetylcholine (ACh)-induced relaxation of the mesenteric artery and the aorta in rats., Methods: The responses of isolated rat aortic and mesenteric arterial ring segments precontracted with phenylephrine to ACh (10(-8)-10(-5) M), in the presence of halothane 0-3%, were compared using isometric force tension recordings. Effects of NG-nitro-l-arginine (L-NOARG, 3 x 10(-5), methylene blue (MB, 5 x 10(-6) M), oxyhaemoglobin in (OxyHB, 10(-7) M), and various potassium channel inhibitors; tetraethylammonium (TEA, 10(-5) M, 10(-3) M), apamin (AP, 10(-7) M), charybdotoxin (ChTx, 10(-7) M) and glibenclamide (GC, 10(-5) M) on ACh-induced relaxation in mesenteric artery were tested. Using radioimmunoassay, ACh (10(-6) M)-induced guanosine 3':5'-cyclic monophosphate (cGMP) accumulation of mesenteric arterial rings pretreated with L-NAORG were also measured., Results: L-NOARG partially inhibited ACh-induced relaxation in mesenteric arterial rings (P < 0.05, maximum relaxation reduced by approximately 50%), whereas it abolished them in aortic rings. The remaining relaxation resistant to L-NOARG in mesenteric arterial rings was insensitive to additional MB or OxyHB, and was not accompanied by increases in cGMP contents of rings. Halothane inhibited endothelium-dependent relaxation in aorta and mesenteric arterial rings. This inhibitory effect was larger in aorta. Halothane also inhibited NO independent EDHF-dependent relaxation in the mesenteric arterial rings,, Conclusion: Despite a similar inhibitory effect on the EDHF relaxing pathway, halothane has a larger effect on endothelium-dependent relaxation in the aorta (NO dependent mainly) than in the mesenteric rings (NO and EDHF dependent).

Background: The objective of this study was to characterize the effects of halothane on the agonist-induced nitric oxide-cyclic GMP (NO-cGMP) mechanisms by comparing the intracellular signal transduction mediating isoproterenol- and acetylcholine-induced nitric oxide formation., Methods: Isoproterenol-induced relaxations of rat aortic rings with and without endothelia were examined in the absence and presence of halothane. Studies were also done in the presence of inhibitors of nitric oxide-synthase, adenylyl cyclase, calmodulin, protein kinase A, and intracellular Ca2+ release mechanism. The relaxations under some of these conditions were compared with those induced by acetylcholine. Cyclic nucleotide contents of the rings were also measured., Results: Isoproterenol relaxed aortic rings via the endothelium-dependent nitric oxide-cyclic GMP mechanism. Inhibition of adenylyl cyclase or of protein kinase A attenuated the isoproterenol-induced relaxations significantly but did not affect those induced by acetylcholine. Inhibition of intracellular Ca2+ release abolished the acetylcholine-induced relaxations but did not affect those induced by isoproterenol. Calmodulin inhibition attenuated both agonist-induced relaxations significantly. Unlike acetylcholine-induced relaxation, that induced by isoproterenol was not affected by halothane. Isoproterenol increased both the cyclic adenosine monophosphate and cGMP contents of rings significantly when endothelia were intact. Inhibition of nitric oxide synthase attenuated the isoproterenol-induced cGMP content increases significantly but did not affect the cyclic adenosine monophosphate content increases. Halothane (2%) did not affect isoproterenol-induced increases in nucleotide content., Conclusions: Isoproterenol-induced nitric oxide formation requires the activation of constitutive nitric oxide synthase, but the Ca2+ release mechanism is not involved in activating this enzyme. Halothane can inhibit the nitric oxide-cyclic GMP mechanism only when Ca2+ release is greatly involved in the activation of constitutive nitric oxide synthase.

Caffeine (10(-4)-10(-3) M) induced concentration-dependent relaxations of phenylephrine-precontracted rat aortic rings with endothelium. Endothelial denudation significantly, but only partially, attenuated caffeine-induced relaxation. Pretreatment with NG-nitro-L-arginine, oxyhemoglobin, and methylene blue attenuated the relaxations to an extent similar to endothelial denudation. Guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) contents of aortic strips with endothelium increased significantly after exposure to caffeine (10(-3) M). Endothelial denudation attenuated caffeine-induced cGMP increase. Pretreatment with ryanodine (2 x 10(-5) M), which has been shown to combine with receptors on endoplasmic reticulum (ER) of endothelium, attenuated caffeine-induced relaxation and cGMP content increase of rings with endothelium. Pretreatment with caffeine potentiated sodium nitroprusside-induced relaxations and cGMP increase of rings without endothelium. These results demonstrated that caffeine-induced relaxation comprises two components. In the endothelium-dependent mechanism, caffeine promotes nitric oxide synthesis in endothelium by release of Ca2+ from ER through a ryanodine-sensitive Ca2+ channel, and the suppression of cGMP degradation also contributes to the relaxation. In the endothelium-independent mechanism, caffeine acts as a 3',5'-cyclic-nucleotide phosphodiesterase inhibitor.

We describe a patient with myotonic dystrophy who underwent cholecystectomy, and developed severe respiratory depression following epidural administration of morphine to provide postoperative analgesia. At preoperative assessment, he demonstrated near normal vital capacity and maximal voluntary ventilation, but the presence of chronic ventilatory failure with a resting value of PaCO2 51 mmHg. Anaesthesia was produced by a combination of epidural and light general anaesthesia without intravenous anaesthetics, narcotics or neuromuscular relaxants. Five hours after epidural administration of 2 mg morphine, the patient developed severe respiratory depression with a PaCO2 of 93 mmHg. Intravenous naloxone resulted in transient improvement in minute volume, suggesting that epidural morphine was responsible for the depression. Epidural morphine can cause unexpected respiratory depression, even at a small dose, because of the sensitivity of the respiratory centre to morphine in patients with myotonic dystrophy.