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Background Ischemic postconditioning (PostC) protects the liver against ischemia-reperfusion (IR) injury. Milrinone, a phosphodiesterase 3 inhibitor, has been reported to exhibit preconditioning properties against hepatic IR injury; however, its PostC properties remain unknown. This study investigated whether milrinone has PostC properties against hepatic IR injury and the roles of phosphatidylinositol 3-kinase (PI3K) and nitric oxide synthase (NOS). Materials and methods Male Wistar rats were separated into six groups: (1) group S: animals that underwent sham operation without ischemia, (2) group C: ischemia followed by reperfusion with no other intervention, (3) group M: milrinone administered immediately after reperfusion, (4) group MW: wortmannin, a PI3K inhibitor, injected before milrinone administration, (5) group MN: l-NAME, a NOS inhibitor, injected before milrinone administration, and (6) group MD, milrinone administered 30 min after reperfusion. Except for group S, all groups underwent 1 h of warm ischemia of median and left lateral lobes, followed by 5 h of reperfusion. Biochemical liver function analysis and histologic examination were performed. Results Serum aspartate aminotransferase, alanine aminotransferase, and lactic dehydrogenase levels, histologic damage scores, and apoptotic rate in group M were significantly lower than those in group C. The inhibition of PI3K or NOS prevented this protective effect. Milrinone administered 30 min after reperfusion did not show obvious protective effects. Conclusions Milrinone-induced PostC protects against hepatic IR injury when it is administered immediately after reperfusion, and PI3K and NOS may play an important role in this protective effect., Journal of Surgical Research, 186(1), pp.446-451; 2014

Peroral endoscopic myotomy (POEM) is a newly developed, less invasive treatment for esophageal achalasia that requires general anesthesia under positive pressure ventilation. In this retrospective case series, we describe the anesthetic management of 28 consecutive patients who underwent POEM for esophageal achalasia. Anesthesia was maintained with sevoflurane and remifentanil under positive pressure ventilation through a tracheal tube. Retained contents in the esophagus were evacuated just before anesthesia induction to prevent regurgitation into the trachea. The POEM procedure was performed using an orally inserted flexible fiberscope. Elevation of end-tidal carbon dioxide after initiating esophageal carbon dioxide insufflation was observed in all patients and was treated by minute adjustments to the ventilation volume. Scopolamine butylbromide-induced tachycardia in one patient was treated with landiolol hydrochloride, which is a short-acting beta 1-selective blocker. Minor subcutaneous emphysema around the neck was observed in one patient. POEM was successfully completed, and tracheas were extubated immediately after the procedure in all patients. Our findings suggest that prevention of aspiration pneumonia during anesthesia induction, preparation for carbon dioxide insufflation-related complications, and treatment of scopolamine butylbromide-induced tachycardia play important roles in safe anesthesia management of POEM for esophageal achalasia.

We investigated the effect of low-dose droperidol on heart rate-corrected QT (QTc) interval and interaction with propofol. Seventy-two patients undergoing upper limb surgery were included in this study. Patients were randomly allocated to one of three groups: group S (n = 24), which received 1 ml saline; group D1 (n = 24), which received 1.25 mg droperidol; or group D2 (n = 24), which received 2.5 mg droperidol. One minute later, fentanyl (3 μg/kg) was administered. Two minutes after fentanyl administration, anesthesia was induced using propofol (1.5 mg/kg) and vecronium. Tracheal intubation was performed 3 min after the administration of propofol. Heart rate, mean arterial pressure, bispectral index, and QTc interval were recorded at the following time points: immediately before the droperidol injection (baseline); 3 min after the saline or droperidol injection; 3 min after the propofol injection; and 2 min after tracheal intubation. Compared to baseline, the QTc interval in group S and group D1 was significantly shorter after propofol injection, but recovered after tracheal intubation. In group D2, the QTc interval was significantly prolonged after droperidol injection, but recovered after propofol injection, and was significantly prolonged after tracheal intubation. We found that saline or 1.25 mg droperidol did not prolong QTc interval, whereas 2.5 mg droperidol prolonged the QTc interval significantly, and that propofol injection counteracted the prolongation of the QTc interval induced by 2.5 mg droperidol.

Objective: To compare acute and long-term postoperative pain and side effects in patients undergoing mastectomy for breast cancer under general anesthesia induced with ketamine or thiamylal. Methods: Twenty four ASA physical status I-III patients undergoing mastectomy were randomly assigned to one of two groups. Ketamine group received intravenous ketamine, 1 mg/kg, and thiamylal group received intravenous thiamylal, 4 mg/kg, at the induction of general anesthesia. Anesthesia was maintained with sevoflurane, N2O and fentanyl. The intensity of pain was assessed by using visual analog scale (VAS) 3 and 16 hr and 2, 3 and 4 weeks after surgery. Postoperative side effects, including nausea, vomiting and hallucination were also recorded. Results: At 16 hr after surgery, VAS in ketamine group was significantly lower than that in thiamylal group. However, there were no statistically significant differences between the two groups in the VAS at 3 hr and 2, 3 and 4 weeks after surgery. There were no differences in the incidence of side effects such as nausea, vomiting and hallucination between the two groups. Conclusion: Intravenous ketamine at the induction of anesthesia could reduce acute postoperative pain but not long-term pain after mastectomy.

Journal of Clinical Anesthesia, 24(6), pp.513-516; 2012

Ultrasound-guided supraclavicular brachial plexus block carries a risk for puncture of vascular structures. In this study, we determined the frequency with which the transverse cervical artery (TCA) and the dorsal scapular artery (DSA) are detected by ultrasound evaluation at 3 probe positions during supraclavicular block.Ultrasound examinations of the supraclavicular region were performed in 53 healthy adult volunteers. Ultrasound images of the supraclavicular region were acquired at 3 probe positions: position A (the brachial plexus and the subclavian artery both lying on the first rib); position B (the brachial plexus on the first rib; the artery on the pleura); and position C (the brachial plexus between the anterior and middle scalene muscles). The primary outcome variables were the frequencies with which TCA and DSA were detected by 2-dimensional and color Doppler imaging at 3 specified probe positions.One hundred six supraclavicular regions were examined in 53 subjects. The subclavian artery was detected in all subjects. TCA was more often detected than DSA, 94 (88.7%, 95% confidence interval [CI] 80.7%-93.8%) and 36 (34%, 95% CI 25.3%-43.9%) of 106 scans, respectively (McNemar P value0.001). TCA was detected in 2 (1.9%, 95% CI 0.3%-7.3%), 31 (29.2%, 95% CI 20.9%-38.9%), and 61 (57.5%, 95% CI 47.5%-66.9%) of scans at probe positions A, B, and C, respectively, whereas DSA was detected in 3 (2.8%, 95% CI 0.7%-8.6%), 23 (21.7%, 95% CI 14.5%-30.9%), and 10 (9.4%, 95% CI 4.8%-17.0%) of scans at probe positions A, B, and C, respectively. Thus, the TCA and DSA were less likely to be present with probe position A (all P0.001).TCA was more often detected than DSA in the vicinity of the brachial plexus in the supraclavicular region. Both TCA and DSA were least likely to be present in probe position A. Color Doppler, particularly for probe position A, may help to reduce the risk for inadvertent vascular puncture during ultrasound-guided supraclavicular block.

麻酔の歴史の始まり以来，全身麻酔は医師のみでなく歯科医師によっても行われてきた．現在のわが国において，年間の全身麻酔件数は約200万件，歯科医師によって行われている件数は約1万5千件と推定される．歯科医師による全身麻酔の法的根拠は歯科医師法に拠っている．歯科医行為の範囲は「歯および口腔の組織臓器の診療」と解釈されるが，歯科医行為を行うための全身麻酔もその範囲と解釈されている．しかし医師が行う医行為に際して歯科医師が全身麻酔を行うと医師法に抵触する．現在のわが国では，歯科医師による医科麻酔は厚生労働省の研修ガイドラインに従う場合にのみ認められている．

Patients undergoing extensive cervical spine surgery (ECSS) occasionally require emergency reintubation due to postoperative airway complications. To avoid it, an endotracheal tube is retained in patients maintained under sedation overnight. This study was conducted to determine whether dexmedetomidine would be superior in sedative effects to propofol for postoperative sedation after ECSS.We studied 32 consecutive patients undergoing ECSS who required prophylactic intubation postoperatively under sedation overnight. The patients were randomly divided into two groups. Group D (n = 16) received dexmedetomidine 0.1 μg/kg/min for 10 min as a loading dose, followed by a continuous infusion at 0.4 μg/kg/h. Group P (n = 16) received propofol 0.1 mg/kg/min for 10 min as a loading dose, followed by a continuous infusion at 1 mg/kg/h. All patients received analgesia with buprenorphine. Ramsay sedation scale, extremity movement, and pain intensity were recorded every 2 h. Dexmedetomidine and propofol dosages were adjusted to maintain a desired sedation level. Nursing staff adjusted dopamine to maintain systolic blood pressure100 mmHg and administered atropine when the heart rate was50 bpm.The proportions of adequate sedation level, movement, and pain status were similar between groups. In group D, heart rates were lower, frequency of atropine use was greater, and dopamine dose was higher than in group P.Both sedatives are efficacious after ECSS; however, dexmedetomidine decreased heart rate and required higher dose of dopamine.

PURPOSE: When neostigmine is used to reverse muscle relaxants in patients with asthma without signs of airway inflammation, asthma attack is occasionally encountered. It is likely that abnormally increased electrical impulses traveling from the brain through cholinergic nerves to airway smooth muscles may be one of the pathogeneses of asthma attack. We applied continuous electrical field stimulation (c-EFS) or continuous electrical stimulation (c-ES) of low frequency to the vagal nerve of the rat in vitro and in vivo to determine the role of cholinergic nerve activation in inducing airway constriction. METHODS: Fifty-seven male Wistar rats were used. In an in vitro study we examined whether tetrodotoxin (TTX), an Na(+)-channel blocker, 4-DAMP, a muscarinic M(3) receptor antagonist, or neostigmine could affect c-EFS-induced contraction of the tracheal ring. In an in vivo study, we examined whether c-ES of the vagal nerve could increase maximum airway pressure (P (max)) and whether neostigmine could potentiate c-ES-induced P (max). RESULTS: TTX and 4-DAMP completely inhibited c-EFS-induced contraction whereas neostigmine potentiated c-EFS-induced contraction dose-dependently. P (max) was not increased by neostigmine. P (max) was not increased by 2-Hz c-ES, but was increased by the addition of neostigmine. P (max) was increased by 5-Hz c-ES, and further increased by the addition of neostigmine. CONCLUSION: The contractile response of the tracheal ring to c-EFS is potentiated by neostigmine. P (max) is increased by c-ES of the vagal nerve, and is potentiated by neostigmine. These data suggest that increased activity of the cholinergic nerve could be involved in asthma attack., Journal of Anesthesia, 26(1), pp.80-84; 2012

生体肝移植患者では肝機能障害に伴う凝固機能障害，門脈圧亢進症のため，手術中に大量出血することがある．今回，生体部分肝移植症例40例を対象とし，周術期ヘモグロビン値（Hb），血小板数，凝固機能検査と術中・術後の出血量，輸血量を後ろ向きに調査した．術中出血量に関しては執刀前のHb，活性化部分トロンボプラスチン時間（APTT）を含む回帰式が得られ，執刀前のHb，プロトロンビン時間（PT-INR），APTTは術中赤血球輸血量との関連性を示した．術後3日間の赤血球輸血量と終刀時凝固機能検査には相関を認めなかった．執刀前のHb，PT-INR，APTTは，術中出血量と輸血量の指標になると考えられる．

It is known that selective cyclooxygenase 2(COX-2) inhibitors increase mortality in patients with previous myocardial infarction, and it has been suggested that COX-2 plays an important role in cardioprotection against ischemia. The current study was carried out to determine whether COX-2 is involved in the mechanisms of sevoflurane- and olprinone-induced early-phase preconditioning (E-PreC) and postconditioning (PostC) in rat hearts., Journal of Cardiovascular Pharmacology and Therapeutics, 16(1), pp.72-78; 2011

PURPOSE: Deliberate mild hypothermia (MHT) is applied for cerebroprotection after cardiopulmonary resuscitation and during cardiac surgery. MHT has been shown to alter both contractility and relaxation of blood vessels in the brain. However, the effects of MHT on drug-induced vasodilation are not fully understood. The aim of this study was to clarify the effects of MHT on the coronary vasodilation induced by cromakalim (an ATP-sensitive K channel opener), S-nitroso acetyl-penicillamine (SNAP; a nitric oxide donor), and isoflurane in isolated rat hearts. METHODS: Male SD rat hearts were isolated and perfused with Krebs-Henseleit buffer. Coronary flow was measured with the coronary perfusion pressure kept at 60 mmHg, and coronary vascular resistance (CVR) was calculated. After cardiac arrest was induced by tetrodotoxin, the hearts were allocated to one of three temperature groups: 37, 34, and 31 degrees C (n = 7 for each). All groups received 0.01, 0.1, and 1.0 muM of either cromakalim or SNAP or were exposed to isoflurane at 1MAC and 2MAC. Finally, 50 mM of adenosine was administered to obtain maximal coronary vasodilation. RESULTS: CVR significantly increased after cardiac arrest, but did not change after the application of each temperature. Cromakalim, SNAP and isoflurane significantly decreased CVR in each temperature group. There were no significant differences in CVR among the three temperature groups with any of the test drugs. CONCLUSION: These results indicate that cromakalim-, SNAP-, and isoflurane-induced coronary vasodilation are not affected by MHT., Journal of Anesthesia, 24(4), pp.564-568; 2010

SUMMARY The aim of this study was to determine the effect of thiamylal and propofol on heart rate-corrected QT (QTc) interval during anaesthetic induction. We studied 50 patients undergoing lumbar spine surgery. Patients were administered 3 microgxkg(-1) fentanyl and were randomly allocated to receive 5 mgxkg(-1) thiamylal or 1.5 mgxkg(-1) propofol as an induction agent. Tracheal intubation was performed after vecuronium administration. Heart rate, mean arterial pressure, bispectral index score, and 12-lead electrocardiogram were recorded at the following time points: just before (T1) and 2 min after (T2) fentanyl administration; 2 min after anaesthetic administration (T3); 2.5 min after vecuronium injection (T4); and 2 min after intubation (T5). Thiamylal prolonged (p < 0.0001), but propofol shortened (p < 0.0001), the QTc interval.

A 43-year-old woman with pulmonary fibrosis secondary to pulmonary alveolar proteinosis was scheduled to undergo lung transplantation. Before the lung transplantation, she had undergone multiple whole-lung lavage procedures on extracorporeal circulation (ECC), which had caused scarring of the right femoral subcutaneous tissues. Preoperative examination revealed a double inferior vena cava (IVC) with interiliac communication, and the left IVC ended at the left renal vein. Surgical exposure of the right femoral vessels was performed immediately after anesthetic induction for emergent vascular access to establish an ECC. Cardiopulmonary collapse did not occur and the ECC was not required until lung resection. The lung transplantation was completed uneventfully. Congenital IVC anomaly is rare, but may make cannulation through the femoral vein difficult. Scarring of the subcutaneous tissue could result in a difficult "percutaneous" approach to the vessels. Evaluation of the vascular anatomy related to the establishment of an ECC is important before lung transplantation., Journal of anesthesia, 23(4), pp.583-586; 2009

PURPOSE: The authors examined whether olprinone, a phosphodiesterase type 3 inhibitor, or isoflurane, a volatile anesthetic, could protect the heart against myocardial infarction in type 2 diabetic rats and whether the underlying mechanisms involve protein kinase C (PKC), mitochondrial ATP-sensitive potassium (m-K(ATP)) channels, or the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. METHODS: All rats underwent 30 min of coronary artery occlusion followed by 2 h of reperfusion. Wistar rats received isoflurane or olprinone before ischemia with or without the PKC inhibitor chelerythrine (CHE), the m-K(ATP) channel blocker 5-hydroxydecanoic acid (5HD), or the PI3K-Akt inhibitor LY294002 (LY). Goto-Kakizaki (GK) rats were randomly assigned to receive isoflurane or olprinone. In another group, GK rats received LY before the olprinone. RESULTS: In the Wistar rats, both isoflurane (38 +/- 11%) and olprinone (40 +/- 11%) reduced infarct size as compared to the control group (59 +/- 8%). In the GK rats, olprinone (41 +/- 9%) but not isoflurane (53 +/- 11%) reduced infarct size as compared to the GK control group (58 +/- 14%). The beneficial effects of olprinone were blocked by LY (58 +/- 14%). In the Wistar rats, CHE, 5HD, and LY prevented isoflurane-induced reductions of infarct size. On the other hand, LY but not CHE or 5HD prevented olprinone-induced reductions of infarct size. CONCLUSIONS: Olprinone but not isoflurane protects the heart against myocardial infarction in type 2 diabetic rats. The olprinone-induced cardioprotective effect is mediated by the PI3K-Akt pathway but not PKC or m-K(ATP) channels., Cardiovascular Drugs and Therapy, 23(4), pp.263-270; 2009

PURPOSE: This study was designed to investigate the action of amitriptyline, a tricyclic antidepressant, on airway smooth muscle reactivity and its underlying mechanisms. METHODS: In isolated rat trachea, isometric force was recorded to examine the effects of amitriptyline on the contractile response to acetylcholine (ACh), electrical field stimulation (EFS), calyculin A (a myosin light chain phosphatase inhibitor), and sphingosylphosphorylcholine (SPC; a Rhokinase activator). In addition, inositol monophosphate (IP1) accumulation was measured to examine its effects on inositol 1, 4, 5-trisphosphate (IP(3)) production during stimulation with ACh. RESULTS: Amitriptyline inhibited the contractile responses to ACh, EFS, calyculin A, and SPC, with the concentrations of amitriptyline (mean +/- SD) required to exert 50% inhibition (IC(50)) being 4.3 +/- 1.3 microM, 3.2 +/- 1.6 microM, 256.4 +/- 106.4 microM, and 98.2 +/- 21.8 microM, respectively. In addition, amitriptyline (10 microM) eliminated the ACh (10 microM)-induced IP(1) accumulation. CONCLUSION: The results suggest that amitriptyline does not influence tracheal smooth muscle reactivity at clinical concentrations ( or =1 microM). The attenuated response to ACh brought about by amitriptyline is presumably due, at least in part, to the inhibition of phosphatidylinositol (PI) metabolism. The ability of amitriptyline to inhibit the calyculin Ainduced contraction suggests that amitriptyline also inhibits the Ca(2+)-calmodulin-myosin light chain pathway independently of the inhibition of PI metabolism. Finally, the difference between the IC(50) values for SPC-induced contraction and those for calyculin A-induced contraction suggests that amitriptyline may also inhibit the Rho-kinase pathway., Journal of anesthesia, 23(3), pp.385-391; 2009

心筋虚血再灌流傷害の制御は周術期管理における重要な課題である. 心筋酸素需給バランスを考慮した全身管理に加え, 薬理学的プレコンディショニング (PPC) の活用が不可欠である. PPCの機序にはアデノシン三リン酸感受性K (KATP) チャネル, mitochondrial permeability transition pore, 活性酸素種, プロテインキナーゼ, 一酸化窒素などが関与している. 吸入麻酔薬とニコランジルはいずれもKATPチャネルを開口させ, PPCによる心筋保護効果を発揮する. 周術期においては加齢, 糖尿病, ある種の麻酔薬など, プレコンディショニング効果を減弱させる多くの因子が影響するため, 複数のKATPチャネル開口薬の併用と周術期の継続的投与により, より確実な心筋保護対策を図るべきである.

エホバの証人に対する帝王切開術の麻酔を, 動脈圧心拍出量 (APCO) から算出した酸素供給量を指標として管理した. 患者は40歳代の女性. 身長150cm, 体重56kg. 子宮筋腫合併高齢出産であったが, 宗教的信条から輸血を拒否したため, 帝王切開術が予定された. 麻酔は0.5%高比重ブピバカインによる脊髄くも膜下麻酔で行い第4胸髄レベル以下の知覚低下を得た. 術後鎮痛は0.2%ロピバカインによる持続硬膜外麻酔で行った. 同種血および自己血輸血は行わず, 貧血による酸素供給量の減少に対して, 輸液および昇圧薬で心拍出量を増加させ代償した. APCOの測定は低侵襲であり, 酸素供給量を指標とした麻酔管理に有用であった.

STUDY OBJECTIVE: To determine the relationship between bispectral index (BIS) and sedation. DESIGN: Prospective, observational clinical study. SETTING: Intensive care unit of a public hospital in Japan. PATIENTS: 22 ASA physical status I, II, and III middle-aged (18-65 yrs) and elderly (>65 yrs) patients receiving postoperative sedation with midazolam. INTERVENTIONS: Patients were allocated to two groups: Group M was composed of middle-aged patients (65 yrs). Midazolam was administered at a bolus dose of 0.1 mg/kg, followed by a continuous dose of 0.04 mg/kg per hour, which was adjusted every two hours to achieve a target level of sedation at 3-6 on the Ramsay Sedation Scale (RSS); buprenorphine was administered at a constant rate (0.625 mug kg(-1) hr(-1)). MEASUREMENTS: BIS value, RSS, midazolam dose, body temperature (BT), heart rate, dopamine dose, and mean arterial pressure were recorded every two hours by an independent nurse. Data were analyzed using Spearman rank correlation and the Mann-Whitney U test. MAIN RESULTS: BIS values decreased depending on depth of sedation; a significant correlation was noted between groups in RSS and BIS. The BIS values at levels of RSS 5 and 6 were significantly lower in Group H than Group M. CONCLUSION: BIS correlated with sedation depth, with BIS scores in group H than group M at a deep sedation depth., Journal of Clinical Anesthesia, 20(7), pp.492-495; 2008

Background and objectiveThis study was carried out to clarify the effect of the combination of acute hypervolaemic haemodilution and hypotensive anaesthesia induced with sevoflurane on human middle cerebral artery flow velocity using transcranial Doppler ultrasonography.MethodsThirty patients who were maintained with N2O–O2–sevoflurane anaesthesia undergoing hip surgery were randomly divided into two groups (no controlled hypotension group, Group A, and controlled hypotension group, Group B). Haemodilution was produced by acute preoperative infusion of 1000 mL of hydroxyethylstarch without removing blood in both groups. Mean arterial pressure was maintained at approximately 95 mmHg in Group A and at 55 mmHg for 80 min by increasing the inspired concentration of sevoflurane in Group B. Middle cerebral artery flow velocity was measured before haemodilution, after haemodilution, 80 min after starting hypotension, and 60 min after recovery from hypotension.ResultsMiddle cerebral artery flow velocity significantly increased in both groups after haemodilution; by 28%, in Group A, P < 0.05 vs. before haemodilution and by 30% vs. before haemodilution in Group B, P < 0.05). During controlled hypotension, it decreased towards the pre-haemodilution value (P < 0.05 vs. after haemodilution).ConclusionsSevoflurane-induced hypotension to a mean arterial pressure of 55 mmHg would reduce middle cerebral artery flow that had been increased by acute hypervolaemic haemodilution, such as haematocrit value of 26%, whereas it could preserve the flow in pre-haemodilution condition during normocapnia.

PURPOSE: The aim of this study was to evaluate the effect of adhesiolysis followed by the injection of steroid and local anesthetic during epiduroscopy on sensory nerve function, pain, and functional disability in patients with chronic sciatica. METHODS: Epidural adhesiolysis, using epiduroscopy, followed by the injection of steroid and local anesthetic, was scheduled in 19 patients with chronic sciatica refractory to lumbar epidural block. Sensory nerve function in the legs was tested with a series of 2000-Hz (Abeta-fiber), 250-Hz (Adelta-fiber), and 5-Hz (C-fiber) stimuli, using the current perception threshold (CPT), and CPT values and intensity of pain and Roland Morris Disability Questionnaire (RMDQ) scores were assessed before and 1 and 3 months after the epiduroscopy. RESULTS: At all frequencies, the CPT values in the affected legs of patients before the epiduroscopy were significantly higher than those in the unaffected legs. Epidural adhesiolysis was successfully performed in 16 of the 19 patients. In these patients, the CPT values at 2000 and 250 Hz, and the pain and RMDQ scores 1 and 3 months after the epiduroscopy were significantly lower than those before the epiduroscopy, while the CPT value at 5 Hz did change. CONCLUSION: Epidural adhesiolysis followed by the injection of steroid and local anesthetic during epiduroscopy alleviated pain, and functional disability, and reduced dysfunction of Abeta and Adelta fibers in patients with chronic sciatica., Journal of anesthesia, 22(3), pp.242-247; 2008

OBJECTIVES: We assessed the effect of administration time for fasudil treatment of the stunned myocardium in 40 anesthetized open chest swine. MATERIALS AND METHODS: All swine were subjected to 12 min ischemia followed by reperfusion to generate stunned myocardium. Group A (n = 11) received saline in place of fasudil both before ischemia and after reperfusion. Group B (n = 10) received 30 min intravenous fasudil at a rate of 13 mug/kg/min starting 45 min before ischemia and received saline after reperfusion. Groups C (n = 10) and D (n = 9) received saline before ischemia, and received fasudil at a rate of 13 microg kg(-1) min(-1) starting just before reperfusion in group C and 30 min after reperfusion in group D. In both groups, treatment lasted 30 min. Myocardial contractility was assessed by percent segment shortening (%SS). RESULTS AND DISCUSSION: Three swine in group A, 2 swine in each of groups B and C, and one swine in group D had ventricular fibrillation or tachycardia after reperfusion and were excluded from further analysis. The changes of %SS from baseline at 90 min after reperfusion in groups B and C were 68 +/- 8% and 75 +/- 8%, respectively, which were significantly higher than in group A or D (47 +/- 10% or 43 +/- 8%). CONCLUSION: We conclude that fasudil administered before ischemia or just after reperfusion, but not 30 min after reperfusion, protects the stunned myocardium., Cardiovascular Drugs and Therapy, 22(4), pp.293-298; 2008

This study was performed to determine the prevalence and the prognostic significance of microalbuminuria in patients admitted to intensive care unit (ICU) after spontaneous intracerebral hemorrhage (ICH). From May 2004 to April 2006, we studied 59 consecutive ICH patients verified using computed tomography and admitted to our ICU within a day after stroke. General clinical, neurologic data, and Glasgow Coma Scale (GCS) were recorded at admission to ICU. Urine was collected at admission to ICU for measuring the urinary microalbumin/creatinine ratio. At hospital discharge, neurologic outcome was assessed using Glasgow Outcome Scale. Among 59 patients, 37 (63%) had unfavorable neurologic outcomes (death, persistent vegetative state, and severe disability). The prevalence rate of microalbuminuria was 85% [95% confidence interval (CI), 76-94]. The areas under the receiver operator characteristic curves showed that the urinary microalbumin/creatinine ratio [0.81 (95% CI, 0.70-0.92)] and the GCS score [0.78 (95% CI, 0.66-0.90)] at admission were significant predictors of unfavorable neurologic outcome at hospital discharge. The threshold value, sensitivity, specificity, and likelihood ratio for the urinary microalbumin/creatinine ratio were 200 mg/g, 51% (95% CI, 39-64), 96% (95% CI, 90-100), and 11.3 (95% CI, 7.9-16.0); and those for the GCS score were 11, 46% (95% CI, 36-61), 96% (95% CI, 90-100), and 10.1 (95% CI, 7.2-14.1), respectively. This study confirmed a high prevalence of microalbuminuria in ICH patients in ICU, and suggested that the urinary microalbumin/creatinine ratio >200 mg/g was comparable to the GCS score

PURPOSE: Gradually progressing contraction of airway smooth muscle is suggested to be due to the Rho-kinase signaling pathway. In our preliminary study in rat tracheas, landiolol, a beta(1)-adrenoceptor antagonist, at high doses caused gradually progressing contraction, and this contraction reached a plateau after 20 min. Therefore, this study was carried out to clarify whether landiolol could stimulate the Rho-kinase pathway or the phosphatidylinositol (PI) response in the rat trachea. METHODS: Seventy-eight male Wistar rats weighing 250-350 g were used for the experiments. Their tracheas were cut into 3-mm-wide ring segments or 1-mm-wide slices. Measurements of isometric tension and [(3)H] inositol monophosphate (IP(1)) production were conducted, using these tracheal rings or slices. Data values are expressed as means +/- SD, and statistical significance (P < 0.05) was determined using analysis of variance (ANOVA). RESULTS: Landiolol (700 microM)-induced contraction was completely inhibited by fasudil at 30 microM, while the landiolol-induced contraction was not inhibited by 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), ketanserin, or nicardipine. Landiolol did not stimulate IP(1) production. CONCLUSION: These results suggest that high concentrations of landiolol could cause airway smooth muscle contraction through the Rho-kinase pathway, but not through the PI response coupled with muscarinic M(3) receptors, 5-HT receptors or the activation of L-type Ca(2+) channels., Journal of anesthesia, 22(1), pp.21-26; 2008

脊髄小脳変性症患者の気管喉頭分離術の麻酔を経験した. 既往歴として声帯の外転障害による上気道の閉塞があり, 気道管理に配慮を要した. 喉頭展開時に観察された声門に異常は明らかでなかったが, 細径の気管チューブでなければ気管挿管は困難であった. 脊髄小脳変性症など多系統萎縮症では, 後輪状披裂筋の麻痺のため上気道の閉塞が起こることがある. 全身麻酔を行う場合には, 声門部の狭窄に注意し, 細径の気管チューブを準備するとともに, 経皮的気管穿刺や気管切開などの準備が必要である.

We aimed to investigate the optimal dose of continuous epidural ropivacaine for effective analgesia with minimal side effects after axillary muscle-sparing thoracotomy.Sixty patients undergoing thoracic surgery via the axillary approach were studied. Patients were given continuous epidural ropivacaine at 6 (group R-6), 9 (group R-9), 12 (group R-12) or 18 mg x h(-1) (group R-18) in a randomized double-blinded fashion after surgery. All of the patients received nonsteroidal anti-inflammatory drugs (NSAIDs) every 6 h for 24 h postoperatively. Pain intensity was assessed under three conditions (at rest, on moving, and while coughing), at 4, 8, 16, 24, and 48 h after surgery, and the extent of sensory block was evaluated at the same time points. The ability of a patient to walk unaided was assessed at 24 and 48 h after surgery.Pain intensity at rest and coughing was significantly higher in group R-6 than in the other groups at 16 h after surgery. Pain intensity during moving was significantly greater in group R-6 than in groups R-12 and R-18 at 16 h after surgery. Group R-18 exhibited a significantly greater extent of sensory block than the other groups. The number of patients who were not able to walk unaided 24 h after surgery was significantly greater in group R-18. There were no significant differences in the incidences of side effects among the groups.Our results showed that epidural analgesia using ropivacaine, at 12 mg x h(-1), provided the best analgesia with few side effects.

Ischemic preconditioning is mediated by the activation of phosphatidylinositol-3-OH kinase-Akt (PI3K-Akt) and by the inhibition of the opening of a mitochondrial permeability transition pore (mPTP) during early reperfusion. Preischemic administration of the phosphodiesterase type III inhibitor olprinone protects the myocardium against infarction, but its mechanism has not been fully clarified. We hypothesized that this olprinone-induced cardioprotective effect was mediated by the activation of PI3K-Akt and by the inhibition of mPTP during early reperfusion.Pentobarbital-anesthetized rats (n = 42) subjected to 30-min coronary occlusion followed by 2-h reperfusion, received olprinone (20 microg.kg(-1)) or saline (control) in the preischemic phase in the presence or absence of the PI3K-Akt inhibitor wortmannin (0.6 mg.kg(-1)) or the mPTP opener atractyloside (5 mg.kg(-1)) before 5 min of reperfusion. The myocardial infarct size was expressed as a percentage of the area at risk. All values were expressed as means +/- SD. Statistical comparisons within groups were made using repeated-measures analysis of variance (ANOVA), followed by a paired t-test, and comparisons among groups were analyzed using a two-way ANOVA, followed by the Tukey-Kramer test.Mean arterial pressure and heart rate showed no significant differences within or among groups. The preischemic administration of olprinone significantly reduced the infarct size (12 +/- 4%) as compared with that in the control group (43 +/- 4%). Wortmannin or atractyloside abolished the protective effect of olprinone (42 +/- 11% or 41 +/- 10%).The olprinone-induced cardioprotective effect could be exerted via the activation of PI3K-Akt and the inhibition of mPTP during early reperfusion.

It is not clear whether fentanyl affects a hyperresponsive airway. We examined the effects of fentanyl on the contractile response of ovalbumin (OA)-sensitized rat tracheas.Rats were sensitized with a single intraperitoneal injection of 10 mug of OA mixed with adjuvant. Fourteen days later, the trachea was cut into 3-mm-wide rings. The OA-induced tension was measured, and the effects of fentanyl were studied in the presence of naloxone. Second, the role of cholinergic nerves and serotonin in the contraction and the effects of fentanyl were examined using tetrodotoxin and ketanserin. Third, lungs of sensitized rats were ventilated, and respiratory system resistance was calculated before and after the administration of OA in the presence of fentanyl.Fentanyl dose-dependently attenuated the OA-induced contraction, and naloxone partly reversed it. Both tetrodotoxin and ketanserin attenuated the contraction. Fentanyl had no further effect on the contraction in the presence of tetrodotoxin, whereas the contraction was nearly abolished by fentanyl in the presence of ketanserin. OA increased respiratory system resistance in sensitized rats, and this effect was attenuated by fentanyl.Fentanyl attenuates the airway hyperresponsiveness of sensitized rat trachea through the inhibition of cholinergic nerves on the smooth muscle.

To determine the prevalence and the prognostic significance of microalbuminuria in patients after aneurysmal subarachnoid hemorrhage (SAH). Prospective and observational clinical study. Multidisciplinary intensive care unit. Fifty-one consecutive patients who underwent aneurysm clipping or endovascular surgery after SAH; 8 patients who underwent surgical clipping for unruptured intracerebral aneurysm served as control. None. General clinical and neurological data were recorded on admission. Urine was collected preoperatively and daily for up to 7 days postoperatively for measuring the urinary microalbumin/creatinine ratio. The Glasgow Coma Scale (GCS) score was also determined on admission and daily for up to 7 days after operation. Neurological outcome was assessed using the Glasgow Outcome Scale (GOS) at 3 months after stroke. The prevalence rates of microalbuminuria were 74.5% in SAH and 37.5% in the control. Among the 51 patients, 25 had unfavorable neurological outcome (GOS 1–3). The areas under the receiver operator characteristic curves showed that the highest urinary microalbumin/creatinine ratio and the lowest GCS score during the first 8 days were the significant predictors of unfavorable neurological outcome. The threshold value, sensitivity, specificity, and likelihood ratio for the highest urinary microalbumin/creatinine ratio were 200 mg/g, 60% [95% confidence interval (CI) 41–79], 96% (95% CI 88–100), and 15.6 (95% CI 9.1–26.7), respectively. This study confirms a high prevalence of microalbuminuria in the SAH patients, and it suggests that the highest urinary microalbumin/creatinine ratio > 200 mg/g during the first 8 days is a significant predictor of unfavorable neurological outcome.

Study Objectives To evaluate the effect of preadministration of flurbiprofen on the plasma concentrations of prostaglandin E2 (PGE2) and postoperative pain. Design Prospective, randomized, controlled and double-blind study. Setting Inpatient surgery at Nagasaki Rosai Hospital. Patients 32 ASA physical status I to II patients scheduled for total knee arthroplasty or open anterior cruciate ligament reconstruction. Interventions Patients were randomly assigned to two groups. Five minutes before tourniquet inflation (350 mmHg), group A (n = 16) received placebo (intralipid, one mL · kg −1 ), and group B (n = 16) received flurbiprofen one mg · kg −1 IV. Catheters were placed in the ipsilateral femoral vein for collection of local blood and in a cubital vein for sampling of systemic blood. Measurements Prostaglandin E2 (femoral vein and cubital vein) was measured before tourniquet inflation (T1), before tourniquet deflation (T2), and immediately after tourniquet deflation (T3). Postoperative analgesia was provided with intravenous buprenorphine, 0.1 mg, on patient demand. Pain (Visual Analog Scale) was assessed at 0.5, one, two, 4, 6, 12 and 24 hours after surgery. Main Results Visual Analog Scale and buprenorphine consumptions in group B were significantly lower than those in group A during the first 4 postoperative hours. In group A, PGE2 in femoral vein increased significantly at T2 (359 ± 105 pg mL −1 , P −1 ) and returned to control values at T3 (252 ± 77 pg mL −1 ), whereas PGE2 in the cubital vein showed no change. In group B, PGE2 in either the femoral vein or cubital vein showed no change throughout the time course. Conclusions Preadministration of flurbiprofen suppresses the local production of PGE2 during tourniquet ischemia, resulting in reduced early postoperative pain in patients undergoing knee surgery.

"Juci", one of the traditional acupuncture techniques, means contralateral acupuncture; i.e., implanting a needle into an acupoint to treat a given disease or disorder, but on the side of the body opposite to the diseased side. The aim of this study was: (1) to assess acupuncture effects on formalin-induced nociceptive behavior in the orofacial region in the rat, and (2) to evaluate the efficacy of Juci in the orofacial formalin test.Forty-four adult male Wistar rats were used in the present study. A 1.0% formalin solution (25 microl s.c., diluted in saline) was injected into the right upper lip. The rats were randomly assigned to five groups. (1) The control group (n = 9), which received formalin injection without acupuncture pretreatment; (2) the ipsilateral Ho-ku (see note below) acupuncture group (n = 10); (3) the contralateral Ho-ku acupuncture group (n = 11); (4) the acupuncture plus naloxone group (n = 9), where intraperitoneal naloxone (1.0 mgxkg(-1)) was injected immediately before acupuncture pretreatment; and (5) the sham acupuncture group (n = 5). "Ho-ku" is the term used for the "Large Intestine 4" acupoint, located between the first and second metacarpal bones.The injection of formalin produced the characteristic biphasic behavioral response. Acupuncture significantly inhibited the response in the early and late phases. Naloxone significantly reversed these effects. There were no statistically significant differences between the ipsilateral and Juci acupuncture groups. Sham acupuncture did not exert any significant effect on the formalin-induced behavior.Our results showed that the degree of effectiveness of Juci was similar to that of the ipsilateral acupuncture technique. Therefore, the Juci technique is also useful for the treatment of orofacial pain.

中心静脈カテーテル挿入は, 救急・集中治療領域において欠かすことのできない処置の一つであるが, 近年, そのカテーテル挿入・留置・管理に伴う事故はインシデント・アクシデントレポートとして取り上げられることも多い. 今回, 中心静脈カテーテルを挿入し, 4日後に椎骨動脈への誤挿入が判明した症例を経験した. 明らかな神経学的合併症を併発することはなかったが, 動脈穿刺, 動脈への薬剤誤注入などの機械的合併症は, 時に重篤な事態に至ることもある. そのため中心静脈カテーテルの挿入・留置に関する統一された適切な確認方法を確立し, また施行する医師も正しい知識, 合併症に対する認識を身につけることが重要である.

We must confirm "instructions for authors" in a medical journal before we submit a manuscript to the journal. Human studies must conform to ethical standards, and be approved by the appropriate Institutional Review Board (IRB). Most "instruction for authors" require to obey "WMA Declaration of Helsinki-Ethical Principles for Medical Research Involving Human Subjects", "Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication" etc. The editors of journal are concerned about appropriate IRB review and informed consent. Lack of appropriate consent or documentation may be grounds for rejection, and we must understand the necessary guidelines before starting a study.

We assessed the dose or timing effect of milrinone administered against myocardial stunning in 37 anesthetized open-chest swine.All swine were subjected to 12-min ischemia followed by reperfusion to produce myocardial stunning. Group A (n = 12) received saline in place of milrinone both before and after ischemia. Group B (n = 9) and C (n = 9) received intravenous milrinone at a rate of 5 microg/kg/min for 10 min followed by 0.5 microg/kg/min for 10 min and 10 microg/kg/min for 10 min followed by 1 microg/kg/min for 10 min, respectively, until 30 min before coronary occlusion. Group D (n = 7) received the same dose of milrinone as group B starting 1 min after reperfusion. Myocardial contractility was assessed by percentage segment shortening (%SS).Five swine in group A and two swine in groups B and C each had ventricular fibrillation or tachycardia after reperfusion, and were thus excluded from further analysis. The percentage changes of %SS from the baseline 90 min after reperfusion in groups B, C, and D were 78 +/- 9%, 82 +/- 13%, and 79 +/- 7%, respectively, which were significantly higher than those in group A (43 +/- 13%).We conclude that milrinone administered before ischemia or just after reperfusion attenuates myocardial stunning.

Aim: This study was carried out to determine the dose–response relationship of the effects of prostaglandin E1 (PGE1) on the nerve root blood flow and the neurologic symptoms after lumbar decompressive surgery using laser Doppler flowmetry. Methods: Fifty-four patients undergoing lumbar laminectomy were randomly assigned to one of three groups. Each group received intravenously one of three test solutions; 10 ml of saline in group A (N = 18), 10 ml of saline containing PGE1, 20 μg, in group B (N = 18), and 10 ml of saline containing PGE1, 50 μg, in group C (N = 18). After lumbar laminectomy, a probe of laser Doppler flowmetry was placed directly on the lumbar nerve root. Nerve root blood flow (RBF) velocity was measured before the injection of test solution (T1), at 5 min (T2) and 10 min (T3) after starting injection, and 10 min after the end of injection (T4). A visual analogue scale (VAS) and the walking distance were measured for assessment of neurologic symptoms before and after surgery. Resu...

Propofol is considered suitable for induction of anesthesia in patients with bronchial asthma. However, the mechanisms of its action on bronchi are not fully understood. We examined the effects of propofol on ovalbumin (OA)-induced contraction of OA-sensitized rat trachea. Male Wistar rats were sensitized by a single intraperitoneal injection of OA 10 microg mixed with aluminum hydroxide, 10 mg, as adjuvant. Fourteen days later, the experiment was performed using the tracheal rings. We observed the effects of ketanserin, a 5-HT2 receptor antagonist, and atropine on OA-induced contraction. Next, the effects of propofol on OA-, serotonin (5-HT)-, acetylcholine-, or electrical field stimulation-induced contractions were observed. OA-induced contraction was 90% attenuated by the combination of ketanserin and atropine. Propofol significantly attenuated OA-induced contraction in a dose-dependent manner. Propofol abolished 5-HT-induced contraction, attenuated acetylcholine-induced contraction, and also almost completely attenuated the enhancement by 5-HT of electrical field stimulation-induced contraction. These results suggest that the mechanism involved in the attenuation by propofol of OA-induced contraction is inhibition of the actions of 5-HT. Propofol should be a useful anesthetic in patients with immunoglobulin E-related asthma.

Postherpetic neuralgia has various clinical features, and the implicated pathophysiologic mechanisms are controversial. This study was carried out to clarify the roles of peripheral sensory nerves in the production of allodynia and ongoing pain. Current perception threshold (CPT) testing was used to evaluate the sensory function.The intensities of ongoing pain and dynamic allodynia were assessed using a numeric rating scale (0-10). Assessment of sensory nerve function was performed by a series of 2,000-, 250-, and 5-Hz stimuli using CPT testing. These measurements were made in ipsilateral and contralateral area.CPTs at all frequencies in the ipsilateral area were significantly higher than those in the contralateral area. There were significant and inverse correlations between the intensity of allodynia and CPTs at all frequencies. No correlation was found between the intensity of ongoing pain and CPTs at any frequency. There was no correlation between the intensity of ongoing pain and the intensity of dynamic allodynia.The intensity of dynamic allodynia in postherpetic neuralgia correlates with the preserved functions of Abeta, Adelta, and C fibers. In contrast, the intensity of ongoing pain does not correlate with either the preserved function of C fibers or the intensity of dynamic allodynia. Therefore, it is suggested that postherpetic neuralgia might be a pain syndrome including both peripheral and central mechanisms.

緩和ケアチームの立ち上げを依頼され, コンサルテーション型のチーム活動を行っている. 紹介理由の87%が痛みの緩和であったが, 呼吸困難, 消化管閉塞, 適応障害などでの紹介もみられた. 活動開始2ヵ月後に行った職種別アンケート調査の結果から, 活動開始にあたっては, 一般病院での緩和ケアの必要性や意義について啓発していくこと, 病棟や主治医とのコミュニケーション方法を確立するさまざまな試みが必要と考えられた. 麻酔科医として緩和ケアチームに参加したが, もともとケアを中心とした医療に携わってきた麻酔科医は, 緩和ケアにおいて重要な役割を果たすことができると考えられた. また緩和ケアの習熟は麻酔の質向上にもフィードバックできると考えられた.

近年, 医療行為におけるリスクマネジメントが強く求められるなかで, 当院では2003年に麻酔前指示票を作成し, 術前絶飲食指示方法を院内で統一した. しかし, 絶飲食の確認が十分になされていないことが判明し, 確認方法も院内統一とした. 今回, 術前絶飲食指示・確認方法の院内統一後に小児の麻酔導入時誤嚥性肺炎を経験し, 適切な術前絶飲食の確認およびその後の迅速な処置と対応により患者家族とのトラブルを避けることができた. 術前絶飲食など必須の処置は, 統一された適切な指示・確認方法を確立することがリスクマネジメントの観点から重要である.

Coupling of functional GABAB receptors (GABABR) to G proteins was investigated with an expression system of baby hamster kidney (BHK) cells and Xenopus oocytes. Fluorescence resonance energy transfer (FRET) analysis of BHK cells coexpressing GABAB1a receptor (GB1aR) fused to Cerulean, a brighter variant of cyan fluorescent protein, and GABAB2 receptor (GB2R) fused to Venus, a brighter variant of yellow fluorescent protein, revealed that GB1aR-Cerulean and GB2R-Venus form a heterodimer. The GABABR agonists baclofen and 3-aminopropylphosphonic acid (3-APPA) elicited inward-rectifying K+ currents in a concentration-dependent manner in oocytes expressing GB1aR and GB2R, or GB1aR-Cerulean and GB2R-Venus, together with G protein-activated inward-rectifying K+ channels (GIRKs), but not in oocytes expressing GB1aR alone or GB2R alone together with GIRKs. Oocytes coexpressing GB1aR + Gαi2-fused GB2R (GB2R-Gαi2) caused faster K+ currents in response to baclofen. Furthermore, oocytes coexpressing GB1aR + GB2R fused to Gαqi5 (a chimeric Gαq protein that activates PLC pathways) caused PLC-mediated Ca2+-activated Cl− currents in response to baclofen. In contrast, these responses to baclofen were not observed in oocytes coexpressing GB1aR-Gαi2 or GB1aR-Gαqi5 together with GB2R. BHK cells and Xenopus oocytes coexpressing GB1aR-Cerulean + a triplet tandem of GB2R-Venus-Gαqi5 caused FRET and Ca2+-activated Cl− currents, respectively, with a similar potency in BHK cells coexpressing GB1aR-Cerulean + GB2R-Venus and in oocytes coexpressing GB1aR + GB2R-Gαqi5. Our results indicate that functional GABABR forms a heterodimer composed of GB1R and GB2R and that the signal transducing G proteins are directly coupled to GB2R but not to GB1R.

Background and objectives: It is known that ropivacaine produces a differential block for sensory and motor nerves with lower toxic potential than bupivacaine. This study was carried out to evaluate the comparative efficacy of ropivacaine and bupivacaine for lumbar epidural block in 16 outpatients with degenerative spinal disease. Methods: The study was performed in a prospective, randomized, double blind and crossover fashion. A single injection of 8 ml of 0.375% or 0.2% ropivacaine or 0.25% bupivacaine was given at the L4-5 interspace. Each subject received all of the test solutions at an interval of one week or more. The upper level of analgesia, pain and motor blockade were evaluated by pin prick, visual analogue scale (VAS), and Bromage scale, respectively, and the recovery times to mobilization, ambulation and spontaneous micturition were measured. Results: There was no significant difference in the upper level of analgesia and the reduction of VAS among the three trials. Bromage scale with...