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.

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.

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.

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.

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.

Propofol-induced relaxation of rat aorta is altered by aging.

BACKGROUND: Propofol causes vasodilation via endothelium-dependent and -independent mechanisms. Because endothelial function is impaired with aging, the effects of propofol on endothelium-dependent vasodilation might be altered by aging. The aim of this study was thus to determine the effects of aging on vascular responses to propofol. METHODS: Young (4-6 weeks old) or adult (16-25 weeks old) rats were anesthetized with sevoflurane. The thoracic aorta was dissected and cut into pieces 3-4 mm in length. In some rings, the endothelium was deliberately removed. The ring segment of the aorta was mounted for isometric force recording at a resting tension of 0.5-1.0 g in a 2 ml organ bath, containing Krebs-Ringer bicarbonate buffer. Arteries were precontracted with phenylephrine, and the function of endothelium was confirmed with acetylcholine. Then, we studied the concentration-dependent effects of propofol in endothelium-intact (control group) and -denuded aortic rings (denuded group), as well as those treated with N(ω)-nitro-L-arginine methylester (L-NAME group). RESULTS: Relaxation due to propofol was observed in the control groups of both young and adult rats in a concentration-dependent manner, but the magnitude of relaxation was significantly greater in young rats. In addition, in young rats, relaxation due to propofol was significantly and equally reduced in both L-NAME and denuded groups at all propofol concentrations that we studied (10(-6)-10(-3) M). In adult rats, relaxation due to propofol was quite similar between control and L-NAME groups at all propofol concentrations, whereas it was significantly reduced in the denuded group. CONCLUSION: These results suggest that endothelium-derived nitric oxide plays an important role in propofol-induced vasodilation in young rats, but not in adult rats.

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.

Mechanisms of action of anesthetics for the modulation of perioperative thrombosis: evidence for immune mechanisms from basic and clinical studies.

Thrombotic events occurring in either arteries or veins are the primary causes of fatal perioperative cardiovascular events. Risk factors for deep vein thrombosis, several of which are evidently associated with specific surgical procedures, are quite different from those for arterial thrombosis (e.g., aging or atherosclerotic diseases). Thrombus formed in arteries consists mainly of platelets coated with fibrin (i.e., white thrombus), while venous thrombus formed at relatively lower shear stress consists of all blood components including erythrocytes as well as leukocytes infiltrated with fibrin (red thrombus). Clinical evidence indicates beneficial roles of neuraxial anesthesia/analgesia in the prevention of VTE for patients undergoing high risk surgical procedures. To date, mechanisms of action of drugs used for neuraxial anesthesia/analgesia to prevent venous thrombosis are uncertain. However, accumulation of clinical as well as experimental findings points to the involvement of immune cells (especially monocytes) in red thrombus generation and to the interaction of anesthetics with these cells. We also suggest that adhesion molecules associated with the formation of monocyte platelet aggregates as well as substance P: neurokinin-1 receptor (SP/NK1R) pathway that involves neurogenic inflammation are crucial. Local anesthetics and NK1R antagonists are candidate drugs that may possess the capability to prevent venous thrombotic disorders in perioperative settings.

The supine-to-prone position change induces modification of endotracheal tube cuff pressure accompanied by tube displacement.

STUDY OBJECTIVES: To determine whether the supine-to-prone position change displaced the endotracheal tube (ETT) and, if so, whether the displacement related to this change modified ETT cuff pressure. DESIGN: Prospective study. SETTING: Operating room of a university hospital. PATIENTS: 132 intubated, adult, ASA physical status 1, 2, and 3 patients undergoing lumbar spine surgery. INTERVENTIONS AND MEASUREMENTS: After induction of anesthesia, each patient's trachea was intubated. The insertion depth of each ETT was 23 cm for men and 21 cm for women at the upper incisors. In the supine position and after the supine-to-prone position change with the head rotated to the right, the length from the carina to ETT tip and ETT cuff pressure were measured. MAIN RESULTS: After the supine-to-prone position change, 91.7% patients had ETT tube displacement. Of these, 48% of patients' ETT moved ≥ 10 mm, whereas 86.3% of patients had changes in tube cuff pressure. There was a slight but significant correlation between ETT movement and change in cuff pressure. Depending on the position change, ETT cuff pressure decreased and the ETT tended to withdraw. CONCLUSIONS: After the supine-to-prone position change, patients had ETT tube displacement. Such ETT movement may be accompanied by a decrease in cuff pressure.

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.

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.

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.

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.

[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.