Cytoskeleton-disrupting agent cytochalasin B reduces oxidative stress caused by high glucose in the human arterial smooth muscle.

The role of cytoskeleton dynamics in the oxidative stress toward human vasculature has been unclear. The current study examined whether the cytoskeleton-disrupting agent cytochalasin B reduces oxidative stress caused by high glucose in the human arterial smooth muscle. All experiments in the human omental arteries without endothelium or the cultured human coronary artery smooth muscle cells were performed in d-glucose (5.5 mmol/L). The exposure toward d-glucose (20 mmol/L) for 60 min reduced the relaxation or hyperpolarization to an ATP sensitive K+ channel (KATP) opener levcromakalim (10-8 to 3 × 10-6 mol/L and 3 × 10-6 mol/L, respectively). Cytochalasin B and a superoxide inhibitor Tiron, restored them similarly. Cytochalasin B reduced the NADPH oxidase activity, leading to a decrease in superoxide levels of the arteries treated with high d-glucose. Also, cytochalasin B impaired the F-actin constitution and the membrane translocation of an NADPH oxidase subunit p47phox in artery smooth muscle cells treated with high d-glucose. A clinical concentration of cytochalasin B prevented human vascular smooth muscle malfunction via the oxidative stress caused by high glucose. Regulation of the cytoskeleton may be essential to keep the normal vascular function in patients with hyperglycemia.

Involvement of superoxide generated by NADPH oxidase in the shedding of procoagulant vesicles from human monocytic cells exposed to bupivacaine.

It is known that a variety of sized procoagulant vesicles that express tissue factor are released from several types of cells including monocytes by mechanisms related to the induction of apoptosis, while it has not yet been evaluated whether superoxide is involved in the production of such vesicles. Here, we report that a local anesthetic bupivacaine induces apoptosis in human monocytic cells THP-1 within a short observation period, where the shedding of procoagulant vesicles is associated. The property as procoagulant vesicles was evaluated using flow cytometry by the binding of FITC-conjugated fibrinogen to vesicles in the presence of fresh frozen plasma and the suppression of this binding by heparin. Bupivacaine (1 mg/ml) increased the apoptotic cells and procoagulant vesicles. LY294002 (100 µM), that inhibits the recruiting of intracellular component of NADPH oxidase to construct the activated form of this enzyme complex, or superoxide dismutase (1500 unit/ml) suppressed bupivacaine-provoked induction of apoptosis and the increase of procoagulant vesicles. We suggest that this simple experimental system is useful to explore the molecular mechanisms of action of superoxide in the shedding of procoagulant vesicles from human monocytic cells.

Isoflurane pretreatment preserves adenosine triphosphate-sensitive K(+) channel function in the human artery exposed to oxidative stress caused by high glucose levels.

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.

Detection of the full-length transcript variant for neurokinin-1 receptor in human whole blood associated with enhanced reinforcement of clot by substance-P.

We have recently reported that a neurotransmitter for pain, substance-P (SP), promotes platelet-dependent clot formation through neurokinin-1 receptors (NK1Rs), in which leukocytes appear to be involved (J Thromb Thrombolysis 2009;27:280-6). Two naturally occurring splice isoforms of NK1R with different signal transduction potency, namely the full-length and the truncated NK1Rs are identified. It is known that human leukocytes express truncated NK1Rs, while in vivo expression of the full-length NK1R has not yet been fully clarified. Modulatory effects of alternative splicing for NK1Rs on clot formation also remain to be evaluated. Expression of the transcript variant mRNA for NK1Rs in human whole blood (n = 20) was evaluated by real-time reverse transcription polymerase chain reaction (RT-PCR). A 15 min time series of the strength of clot, formed after reloading of calcium in citrated whole blood with or without SP (10 nM) and a NK1R antagonist Spantide (1 µM), was measured by using oscillating-probe viscoelastometry. The full-length transcript variant was detected in 5 samples among 20. SP significantly increased the clot strength while Spantide suppressed the SP-derived change. The extent of modulation by SP/NK1R pathway in a subgroup with expression of the full-length transcript variant was three times as potent as those in another subgroup without expression. We conclude that expression of the full-length transcript variant for NK1R can be detected in human whole blood and that such expression is associated with the enhanced reinforcement of clot by SP. Further study is required to nominate this mRNA as a biomarker for prothrombotic risks in painful conditions such as perioperative period.

Molecular mechanisms of the inhibitory effects of clonidine on vascular adenosine triphosphate-sensitive potassium channels.

BACKGROUND: We investigated the effects of the imidazoline-derived α2-adrenoceptor agonist clonidine on vascular adenosine triphosphate-sensitive potassium (K(ATP)) channel activity in rat vascular smooth muscle cells and recombinant vascular K(ATP) channels transiently expressed in COS-7 cells. METHODS: Using the patch-clamp method, we investigated the effects of clonidine on the following: (1) native vascular K(ATP) channels; (2) recombinant K(ATP) channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits; (3) SUR-deficient channels derived from a truncated isoform of the Kir6.2 subunit (Kir6.2ΔC36 channels); and (4) mutant Kir6.2ΔC36 channels with diminished sensitivity to ATP (Kir6.2ΔC36-K185Q channels). RESULTS: Clonidine (≥3 × 10(-8) M) inhibited native K(ATP) channel activity in cell-attached configurations with a half-maximal inhibitory concentration value of 1.21 × 10(-6) M and in inside-out configurations with a half-maximal inhibitory concentration value of 0.89 × 10(-6) M. With similar potency, clonidine (10(-6) or 10(-3) M) also inhibited the activities of various recombinant SUR/Kir6.0 K(ATP) channels, the Kir6.2ΔC36 channel, and the Kir6.2ΔC36-K185Q channel. CONCLUSIONS: Clinically relevant concentrations of clonidine inhibit K(ATP) channel activity in vascular smooth muscle cells. This inhibition seems to be the result of its effect on the Kir6.0 subunit and not on the SUR subunit.

The modulation of vascular ATP-sensitive K+ channel function via the phosphatidylinositol 3-kinase-Akt pathway activated by phenylephrine.

The present study examined the modulator role of the phosphatidylinositol 3-kinase (PI3K)-Akt pathway activated by the alpha-1 adrenoceptor agonist phenylephrine in ATP-sensitive K(+) channel function in intact vascular smooth muscle. We evaluated the ATP-sensitive K(+) channel function and the activity of the PI3K-Akt pathway in the rat thoracic aorta without endothelium. The PI3K inhibitor 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) (10(-5) M) augmented relaxation in response to the ATP-sensitive K(+) channel opener levcromakalim (10(-8) to 3 x 10(-6) M) in aortic rings contracted with phenylephrine (3 x 10(-7) M) but not with 9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin F(2alpha) (U46619; 3 x 10(-8) M), although those agents induced similar contraction. ATP-sensitive K(+) channel currents induced by levcromakalim (10(-6) M) in the presence of phenylephrine (3 x 10(-7) M) were enhanced by the nonselective alpha-adrenoceptor antagonist phentolamine (10(-7) M) and LY294002 (10(-5) M). Levels of the regulatory subunits of PI3K p85-alpha and p55-gamma increased in the membrane fraction from aortas without endothelium treated with phenylephrine (3 x 10(-7) M) but not with U46619 (3 x 10(-8) M). Phenylephrine simultaneously augmented Akt phosphorylation at Ser473 and Thr308. Therefore, activation of the PI3K-Akt pathway seems to play a role in the impairment of ATP-sensitive K(+) channel function in vascular smooth muscle exposed to alpha-1 adrenergic stimuli.

Continuous But Not Pulsed Radiofrequency Current Generated by NeuroTherm NT500 Impairs Mitochondrial Membrane Potential in Human Monocytic Cells THP-1.

BACKGROUND: The application of pulsed radiofrequency (PRF) current to peripheral nerves with conditions related to neuropathic pain is considered to be clinically safe, while it has been reported that the destruction of mitochondria after PRF application was observed by electron microscopy. If it occurs reproducibly, PRF applied to peripheral nerves should provoke neurolysis because the impairment of mitochondria is known as the primary cause of apoptosis. METHODS: Human monocytic cells THP-1 loaded with 100 nM tetramethylrhodamine methyl ester (TMRM), a fluorescent dye that proves the mitochondrial membrane potential (MMP), were exposed to the electric field of continuous radiofrequency (CRF) or PRF current. The TMRM-related fluorescence from THP-1 cells was measured by flow cytometry. RESULTS: The exposure of THP-1 cells to a PRF electric field generated by NeuroTherm NT500 for 15 min with maximum power did not decrease MMP in these cells, nor did it cause the induction of apoptosis. By contrast, the application of CRF current at 70 °C for 3 min significantly decreased MMP and induced apoptosis within 10 min after CRF application. CONCLUSION: We conclude from these findings that PRF application does not provoke mitochondrial injury in various types of mammalian cells because the size and the subcellular structure of the plasma membrane or mitochondria are similar among those. However, the present results cannot address the effect of PRF current on organic structure around the nervous system. Further study is required to solve the question of whether PRF current causes neurolysis or not.

Beneficial effect of propofol on arterial adenosine triphosphate-sensitive K+ channel function impaired by thromboxane.

BACKGROUND: It is not known whether thromboxane A2 impairs adenosine triphosphate (ATP)-sensitive K channel function via increased production of superoxide in blood vessels and whether propofol as a nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor restores this modification. METHODS: Rat aortas without endothelium were used for isometric force recording, measurements of membrane potential, and superoxide production and Western immunoblotting. Vasorelaxation to an ATP-sensitive K channel opener levcromakalim was obtained during contraction to phenylephrine (3 x 10(-7) M) or a thromboxane A2 analogue U46619 (3 x 10(-7) M). In some experiments, aortas were incubated with an ATP-sensitive K channel antagonist glibenclamide, a superoxide inhibitor Tiron, a nonselective NADPH oxidase inhibitor apocynin, a hydrogen peroxide scavenger catalase, a xanthine oxidase inhibitor allopurinol, a thromboxane receptor antagonist SQ29548 or propofol (3 x 10(-7) to 3 x 10(-6) M). RESULTS: Levcromakalim-induced vasorelaxation was abolished by glibenclamide in rings contracted with either vasoconstrictor agent. Tiron, apocynin, and propofol, but not catalase, augmented the vasodilator response as well as the hyperpolarization by levcromakalim in aortas contracted with U46619. Tiron, apocynin, SQ29548, and propofol, but not allopurinol, similarly reduced in situ levels of superoxide within aortic vascular smooth muscle exposed to U46619. Protein expression of a NADPH oxidase subunit p47phox increased in these arteries, and this augmentation was abolished by propofol. CONCLUSIONS: Thromboxane receptor activation induces vascular oxidative stress via NADPH oxidase, resulting in the impairment of ATP-sensitive K channel function. Propofol reduces this stress via inhibition of a NADPH oxidase subunit p47phox and, therefore, restores ATP-sensitive K channel function.

The role of 20-hydroxyeicosatetraenoic acid in cerebral arteriolar constriction and the inhibitory effect of propofol.

BACKGROUND: We conducted this study to examine, in cerebral parenchymal arterioles, whether 20-hydroxyeicosatetraenoic acid (20-HETE) induces constrictor responses via superoxide and whether propofol reduces this constriction. METHODS: Electrical field stimulation or 20-HETE was applied to rat brain slices monitored by computer-assisted microscopy. In some experiments, a Na(+) channel antagonist tetrodotoxin, a 20-HETE synthesis inhibitor HET0016, a superoxide scavenger, Tiron, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors diphenyleneiodonium (DPI) and gp91ds-tat, or propofol was added. The superoxide level in the brain slice and the production rate in the absence of slices were evaluated by dihydroethidium fluorescence or cytochrome c reduction with a superoxide-generating system, respectively. RESULTS: Electrical stimulation induced constriction of the cerebral parenchymal arteriole, whereas this response was abolished by tetrodotoxin, HET0016, Tiron, or DPI. 20-HETE (10(-8)-10(-6) mol/L) produced arteriolar constriction, which was inhibited by Tiron or DPI. Propofol reduced the constriction induced by electrical stimulation or 20-HETE. 20-HETE induced superoxide production in the brain slice, which was reduced by Tiron, gp91ds-tat, or propofol. However, propofol did not alter the superoxide production rate in the absence of brain slices. CONCLUSIONS: Either neuronal transmission-dependent or exogenous 20-HETE seems to induce cerebral parenchymal arteriolar constriction via superoxide production resulting from NADPH oxidase activation. Propofol is likely to prevent this constriction via inhibition of NADPH oxidase, but not by its scavenging effect on superoxide.

Prothrombotic roles of substance-P, neurokinin-1 receptors and leukocytes in the platelet-dependent clot formation in whole blood.

A number of types of non-neuronal cells including leukocytes have been confirmed to possess substance-P and its specific neurokinin-1 receptor (NK1R), while the pathophysiological roles of substance-P in these cells remain to be established. Effects of substance-P through NK1R on platelet-dependent clot formation were evaluated by using an oscillating-probe viscoelastometer. The clot signal, indicative of the clot strength in blood-derived samples, was measured after the stimulation with celite and Ca(2+). Substance-P (10 nM) increased the clot signal of whole blood obtained from healthy volunteers, especially modulating the platelet-dependent distinctive peak in traces of the signal. A NK1R antagonist Spantide (500 nM) blocked such substance-P derived change, suggesting the involvement of platelets in the action of substance-P. In contrast, substance-P did not increase the clot signal of platelet-containing but leukocyte-removed plasma. From these, we conclude that substance-P promotes platelet-dependent clot formation through NK1R, in which leukocytes appear to be involved.

Propofol restores brain microvascular function impaired by high glucose via the decrease in oxidative stress.

BACKGROUND: Vascular dysfunction induced by hyperglycemia has not been studied in cerebral parenchymal circulation. The current study was designed to examine whether high glucose impairs dilation of cerebral parenchymal arterioles via nitric oxide synthase, and whether propofol recovers this vasodilation by reducing superoxide levels in the brain. METHODS: Cerebral parenchymal arterioles in the rat brain slices were monitored using computer-assisted videomicroscopy. Vasodilation induced by acetylcholine (10 to 10 m) was obtained after the incubation of brain slices for 60 min with any addition of l-glucose (20 mm), d-glucose (20 mm), or propofol (3 x 10 or 10 m) in combination with d-glucose (20 mm). Superoxide production in the brain slice was determined by dihydroethidium (2 x 10 m) fluorescence. RESULTS: Addition of d-glucose, but not l-glucose, reduced arteriolar dilation by acetylcholine, whereas the dilation was abolished by the neuronal nitric oxide synthase inhibitor S-methyl-l-thiocitrulline (10 m). Both propofol and the superoxide dismutase mimetic Tempol (10 m) restored the arteriolar dilation in response to acetylcholine in the brain slice treated with d-glucose. Addition of d-glucose increased superoxide production in the brain slice, whereas propofol, Tempol, and the nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase inhibitor apocynin (1 mm) similarly inhibited it. CONCLUSIONS: Clinically relevant concentrations of propofol ameliorate neuronal nitric oxide synthase-dependent dilation impaired by high glucose in the cerebral parenchymal arterioles via the effect on superoxide levels. Propofol may be protective against cerebral microvascular malfunction resulting from oxidative stress by acute hyperglycemia.

[New frontier in perioperative blood component therapy--preface and comments].

The latest revision of Japanese practical guidelines for the blood component therapy, edited by the Ministry of Health, Labour and Welfare of Japan in 2005, consisted of several crucial points including: emergency red cell transfusion for critically ill patients; the computer crossmatch; and non-erythrocyte blood component therapy based on diagnosis for coagulopathy. The guidelines issued by the Japanese Society of Anesthesiologists as well as the Japan Society of Transfusion Medicine and Cell Therapy (2008) further focused on the strategy for perioperative massive blood loss. Seven feature articles following this opening article summarizes the topics for the new frontier in perioperative blood component therapy in Japan.

[Diagnosis and transfusion algorithm for the management of perioperative coagulopathy].

The present article reviewed the management of coagulopathy in the perioperative setting, following the Japanese practical guidelines for the blood component therapy, edited by the Ministry of Health, Labour and Welfare of Japan in 2005. The threshold concentrations of platelets, prothrombin time international normalized ratio (PT-INR) and activated partial thromboplastin time (APTT) were optimized for the perioperative critical care under active and/or microvascular bleeding, based on currently available randomized controlled trials. Discontinuation or modification of anticoagulants as well as antiplatelets is essential for the safe perioperative care. Several factors, including normothermia, normovolemia, as well as the maintenance of plasma calcium levels within normal range, are important for the management of coagulopathy. Platelet counts, PT, APTT, and if possible, other point-of-care testing including thromboelastography and its modified techniques should be performed following visual inspection of abnormal bleeding. The transfusion algorithms based on causal diagnosis of coagulopathy optimize the risk/ benefit ratio of perioperative transfusion therapy.

Enhanced expression of gene coding for ß-endorphin in human monocytic cells exposed to pulsed radio frequency electric fields through thermal and non-thermal effects.

BACKGROUND: The enhanced expression of endogenous opioid peptides, including ß-endorphin, has been implicated in the mechanism of action of pulsed radio frequency (PRF) application in pain modulation. Because thermal effects cannot be separated from the physical property of PRF application to biological tissues, we evaluated whether temperatures higher than that of the normal body temperature (37°C) modulate mRNA expression for the precursor of ß-endorphin, proopiomelanocortin (POMC) in human monocytic cells THP-1. We also attempted to examine whether mechanisms other than thermal effects also modulate such gene expression. METHODS AND RESULTS: The mRNA for POMC in THP-1 cells increased by a 15-minutes incubation at 42°C, 45°C, or 70°C without PRF application as compared with that in cells incubated at 37°C. On the other hand, gene expression for POMC in cells incubated at 20°C as well as at 37°C with PRF application for 15 minutes increased as compared to that in cells incubated at 37°C without PRF application. Continuous radio frequency at 70°C but not PRF provoked apoptotic cell death at 1-2 hour, and necrotic cell death at 24 hours after the RF application. CONCLUSION: A simple experimental system using human monocytic cells in culture demonstrated that a 15 minute elevation of temperature above 37°C enhanced gene expression for POMC in THP-1 cells, while a 15 minute application of PRF to these cells incubated at 37°C or lower, also enhanced gene expression, indicating that temperature-independent mechanisms as well as thermal effects may be involved in such gene expression.

Human serum albumin and oxidative stress in preeclamptic women and the mechanism of albumin for stress reduction.

AIMS: The present study to address one of the mechanisms in preeclampsia, examined whether levels of oxidative stress, human serum albumin, and endothelial function correlate in pregnant women and whether human serum albumin reduces levels of superoxide produced by NADPH oxidase activation in the human vascular smooth muscle cells. MATERIALS AND METHODS: Pregnant women with (Preeclampsia group, n = 33) and without preeclampsia (Normal group, n = 37) were recruited to determine levels of reactive oxygen species (serum diacron-reactive oxygen metabolite [d-ROM]), and the flow-mediated dilation (FMD). Human coronary arterial smooth muscle cells or omental arteries were subjected to evaluate isometric force recordings, levels of superoxide, western immunoblotting, and immunohistochemistry. The superoxide scavenging assay was also performed in a cell-free system. KEY FINDINGS: Women in the preeclampsia group demonstrated lower FMD and higher serum d-ROM values than those in the normal group. There were the inverse correlations between serum levels of d-ROM and the degree of FMD and between serum levels of albumin and those of d-ROM. D-glucose reduced the levcromakalim-induced dilation of human omental arteries, and it increased levels of superoxide and the recruitment of the NADPH oxidase subunit p47phox in human coronary arterial smooth muscle cells. Human serum albumin (0.05 to 0.5 g/dL) prevented these alterations whereas it exerted no superoxide scavenging effect. SIGNIFICANCE: Serum albumin relates to oxidative stress inversely, but to the endothelial function positively, in pregnant women. Human serum albumin appears to reduce oxidative stress via NADPH oxidase inhibition in the human vascular smooth muscle, indicating that the serum level may be a critical determinant of vascular oxidative stress in some human diseases.

Inhibitory effect of high concentration of glucose on relaxations to activation of ATP-sensitive K+ channels in human omental artery.

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.

Use of the laryngeal mask airway in combination with regional anesthesia facilitates induction and emergence from general anesthesia in patients undergoing colorectal surgery.

The laryngeal mask airway (LMA) is selected as an alternative to the endotracheal tube (ETT) when rapid recovery from general anesthesia is considered. However, the clinical significance of this airway for abdominal surgery is unclear. Thus, we evaluated whether the LMA, in combination with regional anesthesia, facilitates the induction of and emergence from general anesthesia in patients undergoing elective colorectal surgery. Anesthesia-controlled time in a ETT/Epidural Anesthesia (EA) group [n = 11; general anesthesia, combined with epidural anesthesia, was maintained by sevoflurane (< 3%) supplemented with a fixed rate of propofol (3 mg/kg/h) under controlled ventilation using the ETT] was compared with that in a LMA/Combined Spinal-Epidural Anesthesia (CSEA) group [n = 10; in combination with spinal-epidural anesthesia, general anesthesia was maintained as the same protocol as the ETT/EA under spontaneous ventilation using the LMA]. Time for airway placement in the LMA/CSEA group was significantly shorter than that in the ETT/EA group. Intervals from the end of surgery until the removal of the airway or the decision to exit the operating room in the LMA/CSEA group were shorter than those in the ETT/EA group. No practical sign of aspiration pneumonia and/or atelectasis was found in patients in either group. Under the circumstance of regional anesthesia being requested for post-surgical pain management, we concluded that the LMA facilitated the emergence from as well as the induction of anesthesia without any practical complication when used for patients in colorectal surgery.

Comparative benefit of preemptively applied thiopental for propofol injection pain: the advantage over lidocaine.

Propofol is one of the most frequently applied intravenous anesthetics for the induction of general anesthesia. However, pain on injection of this agent is a considerable problem in daily anesthesia practice because of its severity. Administration of lidocaine prior to propofol injection is a standard technique for reducing the pain on injection. However, this method provides insufficient pain relief. To evaluate whether pretreatment with an ultra-short acting barbiturate, thiopental, is more effective than with lidocaine, a randomized and single-blinded trial was conducted. Patients (20-65 years old, n = 137) were allocated into six groups, and applied with physiological saline, thiopental (25, 50, 75, or 100 mg), or lidocaine (40 mg) at 30 second prior to propofol injection (1 mg/kg, 1200 ml/h). The patient was interviewed about the degree of pain just after propofol was totally injected. Both thiopental (> or =25 mg) and lidocaine decreased the severity of pain in comparison with physiological saline as evaluated by a six-graded pain score. Lidocaine failed to influence the incidence of pain (from 86% to 55%), although thiopental significantly decreased it to 40% (25 mg), 21% (50 mg), 12% (50 mg), and 0% (100 mg), respectively. Thiopental (> or =50 mg) decreased both the severity and incidence of pain more effectively than lidocaine. A Hill plot analysis of these data, after rearrangement by patient's body weight, estimated that the half-effective dose (ED50) and the ED99 of this drug to block pain on injection of propofol were 0.6 and 1.4 mg/kg, respectively.

Protective effects of anesthetics on vascular function related to K⁺ channels.

K(+) channels play an essential role in the membrane potential of arterial smooth muscle, and also in regulating contractile tone. Especially, in vascular smooth muscle, the opening of adenosine triphosphate (ATP)-sensitive K(+) (KATP) channels leads to membrane hyperpolarization, resulting in muscle relaxation and vasodilation. This activation also plays a role in tissues during pathophysiologic events such as ischemia, hypoxia, and vasodilatory shock. In this review, we will describe the physiological and pathophysiological roles of vascular smooth muscle KATP channels in relation to the effects of anesthetics. Although accumulated evidence suggests that many anesthetics modify the above function of K(+) channels as a metabolic sensor, further studies are certainly needed to resolve certain issues, especially in clinical settings of anesthesia use.