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J-GLOBAL

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Language：Japanese   Publisher：克誠堂出版(株)  

横浜市立大学附属病院では2014年に周麻酔期看護師が業務を開始し、麻酔科医の指示・監督の下、麻酔科の診療の補助を行っている。周麻酔期看護師は院内認定資格であり、業務開始時には各施設でその運用に関する規則を定める必要がある。当院では、それらを業務内規としてまとめ、臨床倫理委員会の承認を得た。管理体制や業務内容、業務を行ううえでの取り決め、責任の所在などについて明らかにし、院内のコンセンサスを得る必要がある。(著者抄録)

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Language：Japanese   Publisher：日本手術医学会  

周術期診療は最もチーム医療が必要とされる診療行為と考えられている。特に、観血的医療行為前に休薬する薬剤に関連したインシデントは複数報告され、周術期の服薬管理において薬剤師の関与の必要性が高まっている。しかし、周術期診療における薬剤師の介入状況は非常に限定的である。横浜市立大学附属病院では、周術期医療の質の向上を目的に「周術期管理センター」が組織され、薬剤師は周術期管理センター設立の構想の段階より参画を行った。業務構築・拡大には多くの課題があったが、多職種連携の強みを活かして課題解決を図ることができた。薬剤師が専門性を発揮できる業務体制の構築と、薬剤に関連した周術期医療の質の向上に寄与することができた。(著者抄録)

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症例は74歳男性で、膵粘液性嚢胞腫瘍に対し、膵頭十二指腸切除術を施行した。抜管は、患者の強い歯の食いしばりなどはなく、円滑に行われた。抜管後、脱落歯の有無を特に意識した口腔内観察は行わなかった。翌朝、術後回診の際に患者本人より右門歯破損の訴えがあり、診察上も歯牙の破損を認めた。破損歯を誤嚥している可能性があるため、胸部および腹部単純X線検査を施行したところ、胃内部に破損歯と思われる異常陰影を認めた。患者の残存門歯の形状から、破損歯の先端は鋭利と予想された。この破損歯が再建した消化管を通過する際に粘膜を損傷する危険性が懸念されたため、内視鏡的に摘出する方針となった。この時点で1度目のX線検査から時間が経過しており、万が一、破損歯が再建部位よりも尾側にある場合には内視鏡下での摘出が困難になるため、再度胸部単純X線検査を施行し、位置を確認した。異常陰影の位置には変化なく、内視鏡下での摘出は可能であると判断され、緊急内視鏡下摘出術が施行された。内視鏡を挿入すると腎内に破損歯を認め、鉗子で容易に回収できた。その際、胃内の破損歯摘出部分やそのほかの上部消化管粘膜にも明らかな出血や粘膜損傷は認められなかった。

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Language：Japanese   Publisher：日本手術医学会  

周麻酔期看護師とは、麻酔にかかわる術前から術後までの医療の流れの中で、患者にとって最善の麻酔が施されるように看護師として麻酔業務を補助する役割を果たす者として、2010年に聖路加国際大学大学院修士課程で養成が開始された。2016年度には横浜市立大学大学院修士課程に同様の教育課程が開講した。筆者は、横浜市立大学大学院周麻酔期看護学分野の1期生として2018年に修士課程を修了し、同年から周麻酔期看護師として活動している。現在までに、本邦では6大学で養成が行われ、各施設で周麻酔期看護師が活動しており、その活動の場はより一層の広がりを見せている。一方、公的には未確立な制度であること、標準化された教育プログラムがないため各養成施設が手探りで実施しているという課題もある。周麻酔期看護学の発展やチーム医療、麻酔医療の安全と質の向上に貢献するためにも、教育の情報を発信・共有していくことは重要である。本稿では筆者が修士課程中に経験した周麻酔期看護学実習について報告する。筆者は、約1年半の実習の中で145症例を経験した。本学では、麻酔科医とマンツーマンで担当麻酔症例の麻酔計画について、綿密なディスカッションを繰り返すことを基本とした実習が行われる。質の担保された周麻酔期看護師の育成にあたり、教育プログラムの確立や実習後の評価方法の確立が今後必要になると考えられた。(著者抄録)

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J-GLOBAL

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BACKGROUND: Appropriate pain management is essential to improve the postoperative recovery after total hip arthroplasty (THA). Various case reports have indicated that anterior quadratus lumborum block (QLB) provides effective postoperative analgesia in lower limb surgeries. However, few randomized controlled trials have confirmed the efficacy of anterior QLB for lower limb surgeries. The aim of this single-center, double-blind, randomized controlled trial is to confirm the efficacy of anterior QLB for postoperative recovery after THA. METHODS: The participants will be randomly assigned to either the anterior QLB or placebo groups, using a set of random numbers for the allocation sequence. Only pharmacists will be aware of the allocations; other investigators will be blinded until study completion. After induction of general anesthesia, anterior QLB will be performed by using 0.25% levobupivacaine or normal saline. Fentanyl will be administered according to blood pressure change during the surgery. The primary outcome will be the quality of recovery 40 score (QoR-40). Secondary outcomes will include the visual analog scale score of pain intensity at rest and movement, intraoperative and postoperative doses of fentanyl, and incidence of postoperative nausea and vomiting. Statistical analysis will be performed by using the Student's t test, Mann-Whitney U test, and Fisher's exact test as appropriate. A P value of less than 0.05 will be considered statistically significant. DISCUSSION: The results of our study will reveal whether anterior QLB is effective for postoperative recovery after THA. TRIAL REGISTRATION: UMIN Clinical Trials Registry, UMIN000032255. Registered on 15 April 2018.

DOI： 10.1186/s13063-020-4090-0

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Language：Japanese  

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PURPOSE: Severe hypotension caused by anesthetic administration for anesthesia induction, which might cause ischemic stroke, myocardial injury, acute kidney injury and postoperative mortality, should be prevented. Anesthesiologists are familiar with ultrasound examination of the internal jugular vein (IJV). This study aimed to clarify whether ultrasonographic IJV evaluation just before induction could predict the occurrence of such hypotension. METHODS: Adult patients undergoing surgery under general anesthesia were enrolled after excluding patients with cardiovascular disease or ASA-PS ≥ III. Ultrasonographic IJV images were recorded in both the supine and 10° Trendelenburg positions immediately before induction. Using these images, IJV area (IJV-A), diameter and change rate with posture were measured. Hypotension during induction was defined as mean BP < 60 mmHg or > 30% decrease from baseline. RESULTS: Hypotension during induction was observed in 37 of 82 patients. IJV-A in the Trendelenburg position was 2.02 ± 0.86 and 1.72 ± 0.68 in the hypotensive and non-hypotensive groups, respectively (P = 0.08). Logistic regression analysis performed using age, use of calcium antagonists, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, baseline mean BP and IJV-A in the Trendelenburg position as variables showed that IJV-A in the Trendelenburg position was an independent predictor of hypotension, with an adjusted odds ratio of 3.11 (95% CI 1.07-9.03, P = 0.04). Area under the curve was 0.595 (95% CI 0.469-0.722) for IJV-A in the Trendelenburg position. CONCLUSION: IJV-A in the Trendelenburg position was an independent predictor of hypotension during induction. Further study is required to examine the diagnostic accuracy of IJV-A as a predictor for hypotension during induction.

DOI： 10.1007/s00540-019-02675-9

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Language：Japanese   Publisher：日本手術医学会  

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Bilateral quadratus lumborum blockade (QLB) using ultrasound guidance has been introduced as an abdominal truncal block to improve postoperative analgesia and quality of recovery (QoR) after abdominal surgery, but efficacy remains controversial. The primary aim of this study was to evaluate the efficacy of posterior QLB on the postoperative QoR, and secondarily to evaluate postoperative pain after gynaecological laparoscopic surgery (LS). This study was a single-centre randomized controlled trial. QLB group patients underwent bilateral posterior quadratus lumborum injections with 25-30 mL of 0.25% levobupivacaine after induction of general anaesthesia; the control group underwent no block. Both groups were administered fentanyl-based intravenous patient-controlled analgesia postoperatively. The postoperative QoR was measured using the Quality of Recovery 40 (QoR-40) questionnaire score; postoperative pain was evaluated using the visual analogue scale (VAS) and the cumulative postoperative fentanyl dose. Thirty-one and 29 patients were randomised to the QLB and control groups, respectively. The intraoperative remifentanil dosage was significantly less in the QLB group. The median (interquartile range) for the QoR-40 score was not different between the groups: 154 (133-168) in the QLB group and 158 (144-172) in the control group. There were no statistically significant differences in secondary outcome variables. Single-shot QLB did not improve the QoR or postoperative pain in patients managed by multimodal analgesia after gynaecological LS.

DOI： 10.1177/0310057X19838765

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DOI： 10.1016/j.bja.2019.01.014

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Kokuseido Publishing Co. Ltd  

A 23-year-old woman developed hypertensive crisis three months previously, and was diagnosed as retroperitoneal massive paraganglioma (extra-adrenal pheo-chromocytoma), with a diameter of 77 mm. Preoperative echocardiography revealed normal cardiac function. The open abdominal surgery might include major vascular surgery because the tumor might have infiltrated into the inferior vena cava and abdominal aorta Therefore, in order to discuss the operative procedure, we held a conference with surgeons in gastroenterology and cardiovascular surgery, nurses and clinical engineers. The surgery was performed under general anesthesia. The tumor did not invade surrounding structures, and simple resection was done. During manipulation of the tumor the patient developed hypertension and tachycardia Severe hypotension (75/ 30 mmHg) followed the resection of the tumor. In addi- tion to volume replacement noradrenaline was administered, but the systolic blood pressure rose only to 80 mmHg In order to treat vasodilatory shock, we started arginine vasopressin infusion at 5 units · hr -1 . Her systolic blood pressure rose to 120 mmHg and was stabilized. The patient was transferred to the intensive care unit (ICU) postoperatively. Her general condition was favorable, and was discharged from the ICU on postoperative day 2. In conclusioa multidisciplinary approach was useful for the perioperative management for resection of massive paraganglioma and arginine vasopressin was effective for refractory hypotension after resection of the tumor.

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23歳女性。後腹膜の巨大パラガングリオーマに対して腫瘍摘出術が予定された。腫瘍が周囲臓器に浸潤している疑いがあったため、術前に関連診療科、手術室看護師、臨床工学技士との合同カンファレンスを行い、対策を検討した。結果的には単純摘出であったが、摘出後に血管拡張性ショックを認めたため、ノルアドレナリンに加えバソプレシンを投与したところ、循環動態は安定した。その後の経過は良好で、術後16日目に退院となった。

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Kokuseido Publishing Co. Ltd  

A 32-year-old man underwent awake craniotomy for oligodendroglioma The patient received general anesthesia and had a laryngeal mask inserted to secure airway, and continuous infusion of propofol and remifentanil was started. After induction of anesthesia the patient developed seizure without obvious causes. To prevent seizure, phenytoin was administered. About seven hours after the induction of anesthesia infusion of propofol and remifentanil was discontinued to awake the patient The patient could not communicate adequately for thirty minutes from discontinuation of anesthetics, and developed complicated laryngospasm. Because of laryngospasm, we could not ventilate, and the patient's end tidal CO2 level increased to 60 mmHg. The patient's brain showed swelling rapidly and bleeding inside the tumor. Then we decided to convert to general anesthesia Although the tumor was excised partially, the patient did not show dysphasia after the operatioa The causes of insufficient emergence were thought to be prolonged infusion of propofol or administration of phenytoin, or effect of seizure. In such a case we should decide to convert to general anesthesia early, and prevent worsening the conditions.

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PECS block is a regional anesthesia for anterior chest wall. We present herein the case of 64-year-old woman who underwent partial mastectomy and axillary lymph node biopsy for left breast cancer complicated by interstitial pneumonia due to preoperative chemotherapy. We performed PECS-II block avoiding general anesthesia to prevent acute exacerbation of interstitial pneumonia During the operatioa she was lightly sedated using dexmedetomidine. Additional local anesthesia (1% lidocaine 1 ml) was performed during axillary lymph node biopsy. No oxygen was necessary and no evident symptoms of acute exacerbation of the interstitial pneumonia was observed in the perioperative period. Avoidance of general anesthesia by PECS block might be beneficial for the patients with interstitial pneumonia.

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Language：English   Publisher：FEDERATION AMER SOC EXP BIOL  

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Background: We previously reported a tele-anesthesia system that connected Sado General Hospital (SGH) to Yokohama City University Hospital (YCUH) using a dedicated virtual private network (VPN) that guaranteed the quality of service. The study indicated certain unresolved problems, such as the high cost of constantly using a dedicated VPN for tele-anesthesia. In this study, we assessed whether use of a best-effort system affects the safety and cost of tele-anesthesia in a clinical setting. Methods: One hundred patients were enrolled in this study. We provided tele-anesthesia for 65 patients using a guaranteed transmission system (20 Mbit/s; guaranteed, 372,000 JPY per month: 1 JPY = US$0.01) and for 35 patients using a best-effort system (100 Mbit/s; not guaranteed, 25,000 JPY per month). We measured transmission speed and number of commands completed from YCUH to SGH during tele-anesthesia with both transmission systems. Results: In the guaranteed system, anesthesia duration was 5780 min (88.9 min/case) and surgical duration was 3513 min (54.0 min/case). In the best-effort system, anesthesia duration was 3725 min (106.4 min/case) and surgical duration was 2105 min (60.1 min/case). The average transmission speed in the best-effort system was 17.3 ± 3.8 Mbit/s. The system provided an acceptable delay time and frame rate in clinical use. All commands were completed, and no adverse events occurred with both systems. Discussion: In the field of tele-anesthesia, using a best-effort internet VPN system provided equivalent safety and efficacy at a better price as compared to using a guaranteed internet VPN system.

DOI： 10.1155/2018/9615264

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In patients with amyotrophic lateral sclerosis (ALS), general anesthesia carries a significant risk of respiratory complications and may result in prolonged intubation. Epidural anesthesia may be a feasible alternative in selected cases but may impair respiratory function by producing intercostal muscle weakness. Here, we present a case of ALS who underwent emergency laparotomy that was successfully managed with epidural anesthesia and non-invasive positive pressure ventilation.

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(株)メディカル・サイエンス・インターナショナル  

DOI： 10.11477/mf.3101200195

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE PUBLICATIONS LTD  

We studied the use of tele-anaesthesia between Sado General Hospital (SGH) located on Sado Island and Yokohama City University Hospital (YCUH) located in mainland Japan. The two sites were connected via a virtual private network (VPN). We investigated the relationship between the bandwidth of the VPN and both the frame rate and the delay time of the tele-anaesthesia monitoring system. The tool used for communication between the two hospitals was free videoconferencing software (FaceTime), which can be used over Wi-Fi connections. We also investigated the accuracy of the commands given during teleanaesthesia: any commands from the anaesthetist at the YCUH that were not carried out for any reason, were recorded in the anaesthetic records at the SGH. The original frame rate and data rate at the SGH were 5fps and approximately 18 Mbit/s, respectively. The frame rate at the transmission speeds of 1, 5 and 20 Mbit/s was 0.6, 1.6 and 5.0fps, respectively. The corresponding delay time was 12.2, 4.9 and 0.7s. Twenty-five adult patients were enrolled in the study and tele-anaesthesia was performed. The total duration of anaesthesia was 37 hours. All 888 anaesthetic commands were completed. There were 7 FaceTime disconnections, which lasted for 10min altogether. Because no commands needed to be given during the FaceTime disconnection, the telephone was not used. The anaesthesia assistance system might form part of the solution to medical resource shortages.

DOI： 10.1177/1357633X14562735

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Children with complex congenital heart diseases often require repeated cardiac catheterization; however, children are more radiosensitive than adults. Therefore, radiation-induced carcinogenesis is an important consideration for children who undergo those procedures. We measured entrance skin doses (ESDs) using radio-photoluminescence dosimeter (RPLD) chips during cardiac catheterization for 15 pediatric patients (median age, 1.92 years; males, n = 9; females, n = 6) with cardiac diseases. Four RPLD chips were placed on the patient's posterior and right side of the chest. Correlations between maximum ESD and dose-area products (DAP), total number of frames, total fluoroscopic time, number of cine runs, cumulative dose at the interventional reference point (IRP), body weight, chest thickness, and height were analyzed. The maximum ESD was 80 +/- 59 (mean +/- standard deviation) mGy. Maximum ESD closely correlated with both DAP (r = 0.78) and cumulative dose at the IRP (r = 0.82). Maximum ESD for coiling and ballooning tended to be higher than that for ablation, balloon atrial septostomy, and diagnostic procedures. In conclusion, we directly measured ESD using RPLD chips and found that maximum ESD could be estimated in real-time using angiographic parameters, such as DAP and cumulative dose at the IRP. Children requiring repeated catheterizations would be exposed to high radiation levels throughout their lives, although treatment influences radiation dose. Therefore, the radiation dose associated with individual cardiac catheterizations should be analyzed, and the effects of radiation throughout the lives of such patients should be followed.

DOI： 10.1093/jrr/rru050

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

Pulmonary hypertension (PH) is associated with significant morbidity and mortality. Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP) have pulmonary vasodilatory and positive inotropic effects via receptors VPAC1 and VPAC2, which possess a similar affinity for both peptides, and PAC1, a PACAP-preferring receptor. VIP is a promising option for PH treatment; however, various physiological effects of VIP have limited its clinical use. We investigated the effects of VPAC1 and VPAC2 selective agonists VIP and PACAP to explore more appropriate means of treatment for PH. We examined hemodynamic changes in right ventricular systolic pressure (RVSP), systemic blood pressure (SBP), total pulmonary resistance index (TPRI), total systemic resistance index, and cardiac index (CI) in response to their agonists with monocrotaline (MCT)-induced PH and explored involvement of VIP/PACAP expression and receptors in PH. Sprague-Dawley rats were divided into the MCT group (administered MCT 60 mg/kg) and control group. In MCT-induced PH, decreased VIP and PACAP were associated with upregulation of VPAC1, VPAC2, and PAC1 in lung tissues. Intravenous injection of VPAC2-selective agonist BAY 55-9837 and VIP, but not [Ala(11,22,28)] VIP, improved the CI. The decrease in SBP with VPAC2 agonist was significantly less than that in the control. Although they decreased SBP, these agonists hardly affected RVSP in the control. Activation of VPAC2 receptor with BAY 55-9837 effectively improved RVSP, TPRI, and CI in MCT-induced PH, suggesting a VPAC2 agonist as a possible promising treatment for PH.

DOI： 10.1152/japplphysiol.00861.2013

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Language：English   Publisher：FEDERATION AMER SOC EXP BIOL  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：IOS PRESS  

BACKGROUND: An unintended bolus is delivered by the syringe pump if intravenous line occlusion is released in an inappropriate manner.
OBJECTIVE: The aim of this study was to measure the amount of flushed fluid when an occlusion is inappropriately released and to assess the effect of different syringe pump settings (flow rate, alarm setting, size of syringe and syringe pump model) on the flushed amount.
METHODS: After the stopcock was closed, infusions were started with different model syringe pumps (Terufusion (R) TE312 and TE332S), different syringe sizes or at different alarm settings. After the occlusion alarm sounded, the occlusion was released and the amount of fluid emerging from the stopcock was measured.
RESULTS: The bolus was significantly lower when the alarm was set at a low-pressure setting. The bolus was significantly lower with a 10-ml than a 50-ml syringe. A significant difference was seen only when a 50-ml syringe was used (TE312: 1.99 +/- 0.16 ml vs. TE332S: 0.674 +/- 0.116 ml, alarm High, p &lt; 0.001).
CONCLUSION: To minimize the amount of accidentally injected medication, a smaller syringe size and a low alarm setting are important. Using a syringe pump capable of reducing the inadvertently administered bolus may be helpful.

DOI： 10.3233/THC-130754

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DOI： 10.1016/j.radmeas.2012.05.009

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A 15-year-old boy with subarachnoid hemorrhage was planned for emergency cerebral aneurysm clipping under general anesthesia. He had different blood pressure between the upper limbs and we found coarctation of the aorta at left subclavian artery bifurcation in the preoperative angiography. To prevent re-rupture of cerebral aneurysm and ischemia of abdominal organs, we monitored arterial blood pressure in bilateral radial arteries and non-invasive blood pressure in the left thigh, and his blood pressure was maintained within 120-150 mmHg of systolic pressure in the right radial artery and 50-70 mmHg of mean arterial pressure in the left radial artery and the left thigh during general anesthesia. The preoperative period elapsed uneventfully and the patient was planned for repair of coarctation of the aorta after discharge.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Although several cases of radiation-induced skin injury (RSI) have been reported in association with neurointerventional procedures, such as endovascular embolization for cerebral aneurysm, the absorbed doses are not directly measured in most cases. We therefore built a direct measurement system in order to simplify determination of the entrance skin dose (ESD) during neurointerventional procedures. This system was then applied to patients undergoing long and repetitive procedures in order to establish the efficacy of precise mapping of ESDs using a number of radiophotoluminescence glass dosimeters (RPLDs) and to avoid RSI. We also analyzed the correlation between maximum ESDs and angiographic parameters in order to estimate maximum ESD in real-time.
ESD was measured in 35 procedures in 34 cerebral aneurysm patients with a median age of 65 years (range, 38-79 years). Patients were measured for ESDs while wearing a fitted dosimetry cap equipped with 60 RPLD chips throughout the procedure. Angiographic parameters, including total fluoroscopic time and dose-area product (DAP), were recorded. The Pearson correlation test was used to determine the relationship between maximum ESD and each parameter.
Five of thirty-five procedures showed temporal epilation (14.3%). The correlations between a patient's maximum ESD and total fluoroscopic time and DAP were r = 0.7372, P &lt; 0.001 and r = 0.6698, P &lt; .001, respectively.
We concluded that the regional ESD with geometric information could be obtained by applying the RPLDs. Although this passive dosimetry system may not entirely prevent RSI in real-time, precise dose mapping accompanied by monitoring of angiographic parameters during the procedure should contribute to reducing X-ray dose accumulation in repeated prophylactic endovascular embolization for asymptomatic cerebral aneurysm. (C) 2011 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.radmeas.2011.08.008

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

Ca2+/calmodulin (CaM)-dependent phosphorylation of myosin regulatory light chain (RLC) in smooth muscle by myosin light chain kinase (MLCK) and dephosphorylation by myosin light chain phosphatase (MLCP) are subject to modulatory cascades that influence the sensitivity of RLC phosphorylation and hence contraction to intracellular Ca2+ concentration ([Ca2+](i)). We designed a CaM-sensor MLCK containing smooth muscle MLCK fused to two fluorescent proteins linked by the MLCK CaM-binding sequence to measure kinase activation in vivo and expressed it specifically in mouse smooth muscle. In phasic bladder muscle, there was greater RLC phosphorylation and force relative to MLCK activation and [Ca2+](i) with carbachol (CCh) compared with KCl treatment, consistent with agonist-dependent inhibition of MLCP. The dependence of force on MLCK activity was nonlinear such that at higher concentrations of CCh, force increased with no change in the net 20% activation of MLCK. A significant but smaller amount of MLCK activation was found during the sustained contractile phase. MLCP inhibition may occur through RhoA/Rho-kinase and/or PKC with phosphorylation of myosin phosphatase targeting subunit-1 (MYPT1) and PKC-potentiated phosphatase inhibitor (CPI-17), respectively. CCh treatment, but not KCl, resulted in MYPT1 and CPI-17 phosphorylation. Both Y27632 (Rho-kinase inhibitor) and calphostin C ( PKC inhibitor) reduced CCh-dependent force, RLC phosphorylation, and phosphorylation of MYPT1 (Thr694) without changing MLCK activation. Calphostin C, but not Y27632, also reduced CCh-induced phosphorylation of CPI-17. CCh concentration responses showed that phosphorylation of CPI-17 was more sensitive than MYPT1. Thus the onset of agonist-induced contraction in phasic smooth muscle results from the rapid and coordinated activation of MLCK with hierarchical inhibition of MLCP by CPI-17 and MYPT1 phosphorylation.

DOI： 10.1152/ajpcell.90645.2007

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

We designed the present experiments to investigate the involvement of endogenous nitric oxide synthase (NOS) inhibitors, dimethylarginine dimethylaminohydrolase (DDAB) as a hydrolyzing enzyme of the NOS inhibitors, NOS, arginase which shares L-arginine as a common substrate with NOS, and endothelin-1 (ET-1) in the pulmonary dysfunction after induction of experimental subarachnoid hemorrhage (SAH) in the rabbit. SAH was induced by injecting autologous blood into the cisterna magna, and controls were injected with saline. On day 2, pulmonary arteries were isolated for determinations. A significant impairment of the endothelium-dependent relaxation (EDR) caused by acetylcholine was found in 20 cases (43.5%) out of 46 SAH animals, and the same animals exhibited accompanying the significantly impaired cyclic GMP production, accumulated endogenous NOS inhibitors, attenuated DDAH activity, enhanced arginase activity and accumulated ET-1 within the vessel wall. Meanwhile, there were no differences in endothelial NOS activity per se and sodium nitroprusside-induced relaxation between the animals with an impaired EDR and those without such a change. ET-1 content within aortic wall was increased with concomitant decrease in cyclic GMP production after the intraperitoneal application of authentic monomethylarginine as a NOS inhibitor in the rat. The current results suggest that accumulated endogenous NOS inhibitors and enhanced arginase activity possibly bring about the impaired NO production, thereby attenuating the EDR and contributing to the accumulation of ET-1 within the vessel wall. The accumulated endogenous NOS inhibitors at least partly result from the decreased DDAH activity. These alterations may be relevant to the pulmonary dysfunction after induction of SAH. (C) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.vph.2007.11.002

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The present study was designed to investigate whether endothelial intracellular calcium concentration ([Ca2+](i)), endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) generation altered in association with impaired endothelium-dependent relaxation (EDR) in pulmonary artery (PA) specimens from experimental subarachnoid hemorrhage (SAH) rabbits. Injecting non-heparinized autologous arterial blood into cisterna magna induced the SAH. Simultaneous measurements of enclotbelial [Ca2+](i) and isometric tension of PA specimens were performed using fura 2. The subjects included normal control rabbits (group N), SAH rabbits with normal EDR (group A) and with impaired EDR (group B). When treated with 10(-7) M acetylcholine (ACh), endothelial [Ca2+](i) was significantly lower in group B (74.1 +/- 8.5 nM) than that in groups A (153.0 +/- 28.0 nM, p &lt; 0.05) and N (184.8 +/- 27.8 nM, p &lt; 0.01). Basal and ACh-stimulated cyclic GMP productions as a marker of NO generation were also significantly (p &lt; 0.005) decreased in group B as compared to those in the other two groups. Meanwhile, there were no differences in eNOS activity per se among the three groups. These results suggest that the attenuated endothelial [Ca2+](i) elevation leads to the impaired NO generation in PA endothelium, which in turn impairs the EDR and possibly increases the vascular resistance of PA following SAH. (C) 2007 Published by Elsevier Inc.

DOI： 10.1016/j.vph.2007.04.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC  

Excitation-contraction (E-C) coupling and Ca2+-induced Ca2+ release in smooth and cardiac muscles is mediated by the L-type Ca2+ channel isoform Ca(v)1.2 and the ryanodine receptor isoform RyR2. Although physical coupling between Ca(v)1.1 and RyR1 in skeletal muscle is well established, it is generally assumed that Ca(v)1.2 and RyR2 do not directly communicate either passively or dynamically during E-C coupling. In the present work, we re-examined this assumption by studying E-C coupling in the detrusor muscle of wild type and Homer1(-/-) mice and by demonstrating a Homer1-mediated dynamic interaction between Ca(v)1.2 and RyR2 using the split green fluorescent protein technique. Deletion of Homer1 in mice (but not of Homer2 or Homer3) resulted in impaired urinary bladder function, which was associated with higher sensitivity of the detrusor muscle to muscarinic stimulation and membrane depolarization. This was not due to an altered expression or function of RyR2 and Ca(v)1.2. Most notably, expression of Ca(v)1.2 and RyR2 tagged with the complementary C- and N- terminal halves of green fluorescent protein and in the presence and absence of Homer1 isoforms revealed that H1a and H1b/c reciprocally modulates a dynamic interaction between Ca(v)1.2 and RyR2 to regulate the intensity of Ca2+-induced Ca2+ release and its dependence on membrane depolarization. These findings define the molecular basis of a "two-state" model of E-C coupling by Ca(v)1.2 and RyR2. In one state, Ca(v)1.2 couples to RyR2 by H1b/c, which results in reduced responsiveness to membrane depolarization and in the other state H1a uncouples Ca(v)1.2 and RyR2 to enhance responsiveness to membrane depolarization. These findings reveal an unexpected and novel mode of interaction and communication between Ca(v)1.2 and RyR2 with important implications for the regulation of smooth and possibly cardiac muscle E-C coupling.

DOI： 10.1074/jbc.M611529200

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：COMPANY OF BIOLOGISTS LTD  

Disruption of protein synthesis and folding results in ER stress, which is associated with the pathophysiology of diverse diseases affecting secretory and muscle cells. Cells are protected against ER stress by activation of the unfolded protein response (UPR) that is regulated by the protein kinase PERK, which phosphorylates the translation initiation factor 2 eIF2 alpha to attenuate protein synthesis. PERK-/- cells are unable to modulate ER protein load and experience high levels of ER stress. In addition to its role in protein synthesis, the ER also orchestrates many signaling events essential for cell survival, prominent among which is Ca2+ signaling. It is not known, however, whether there is a relationship between ER stress and the function of the Ca2+ signaling pathway in muscle and nonmuscle cells. To directly address this question we characterized Ca2+ signaling in the secretory pancreatic and parotid acinar cells and in urinary bladder smooth muscle (UBSM) cells obtained from PERK-/- and wild-type mice. Deletion of PERK that results in high levels of ER stress, and distention and fragmentation of the ER slowed the rate of agonist-mediated Ca2+ release from the ER and reduced Ca2+-induced Ca2+ release, although IP3 production, localization of the IP3 receptors, IP3-mediated Ca2+ release, Ca(v)1.2 current and RyRs activity remained unaltered. On the other hand, ER stress disrupted the integrity of the Ca2+-signaling complexes in both secretory and UBSM cells, as revealed by markedly reduced coimmunoprecipitation of plasma membrane- and ER-resident Ca2+-signaling proteins. These findings establish a relationship between the unfolding protein response, ER stress and Ca2+ signaling and highlight the importance of communication within the terminal ER-plasma membrane microdomain for propagation of the Ca2+ signal from the plasma membrane into the cell.

DOI： 10.1242/jcs.02731

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Language：English   Publisher：JAPANESE PHARMACOLOGICAL SOC  

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Language：English   Publisher：FEDERATION AMER SOC EXP BIOL  

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Ca2+/calmodulin (CaM)-dependent phosphorylation of myosin regulatory light chain (RLC) by myosin light chain kinase (MLCK) initiates smooth muscle contraction and regulates actomyosin-based cytoskeletal functions in nonmuscle cells. The net extent of RLC phosphorylation is controlled by MLCK activity relative to myosin light chain phosphatase activity. We have constructed a CaM-sensor MLCK where Ca2+-dependent CaM binding increases the catalytic activity of the kinase domain, whereas coincident binding to the biosensor domain decreases fluorescence resonance energy transfer between two fluorescent proteins. We have created transgenic mice expressing this construct specifically in smooth muscle cells to perform real-time evaluations of the relationship between smooth muscle contractility and MLCK activation in intact tissues and organs. Measurements in intact bladder smooth muscle demonstrate that MLCK activation increases rapidly during KCl-incluced contractions but is not maximal, consistent with a limiting amount of cellular CaM. Carbachol treatment produces the same amount of force development and RLC phosphorylation, with much smaller increases in [Ca2+](i) and MLCK activation. A Rho kinase inhibitor suppresses RLC phosphorylation and force but not MLCK activation in carbachol-treated tissues. These observations are consistent with a model in which the magnitude of an agonist-mediated smooth muscle contraction depends on a rapid but limited Ca2+/CaM-dependent activation of MLCK and Rho kinase-mediated inhibition of myosin light chain phosphatase activity. These studies demonstrate the feasibility of producing transgenic biosensor mice for investigations of signaling processes in intact systems.

DOI： 10.1073/pnas.0308742101

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Language：English   Publisher：BIOPHYSICAL SOCIETY  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

This study investigated whether activated protein C (APC) improves the cerebral vasospasm in an experimental subarachnoid hemorrhage that was produced by the intracisternal injection of autologous blood. Male rabbits were divided into the following four groups: APC 0.1- and 0.5-mg groups, in which 0.1 and 0.5 mg APC were injected into the cisterna magna, respectively; a placebo group, in which saline was injected instead of APC; and a sham operation group that did not get injections of autologous blood, APC, and saline. On day 2, amount of clot in the basal cistern was significantly (p &lt; 0.01) decreased in the APC 0.5-mg group. Percent diameter of the basilar artery on day 2 to that before injecting the blood was angiographically determined as 97.1 +/- 3.8% in the APC 0.5-mg group, which was significantly (p &lt; 0.001) greater than the corresponding value in the placebo group (74.8 +/- 3.4%). The impaired endothelium-dependent relaxation following subarachnoid hemorrhage was normalized in the APC 0.5-mg group (p &lt; 0.0001). These results suggest that APC would improve cerebral vasospasm following subarachnoid hemorrhage, possibly by decreasing the amount of subarachnoid clot and normalizing the impaired nitric oxide production/release.

DOI： 10.1097/00005344-200205000-00014

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Language：English   Publisher：JAPANESE PHARMACOLOGICAL SOC  

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Language：Japanese   Publisher：スパズム・シンポジウム事務局  

今回APC 0.5mg投与で脳血管攣縮率の改善,クモ膜下残存血腫量の減少,脳底動脈の内皮依存性弛緩反応の改善が得られ,又,APC 0.1mg投与でも内皮依存性弛緩反応の改善が認められた.以上よりAPCによって血腫を溶解・除去することで脳血管攣縮を改善し得ることが示唆された

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In the rabbit subarachnoid hemorrhage (SAH) model, the sensitivity of spastic basilar arteries to nitric oxide (NO) was enhanced whereas the endothelial function to release/ produce NO became impaired, as described previously. We assumed from these results that low-dose NO might selectively dilate spastic arteries without influencing normal or systemic blood vessels; therefore, we investigated whether exogenous low-dose NO effectively improves cerebral vasospasm. Low-dose NO was derived from a small size of the tape containing nitroglycerin, which is not invasive and is clinically available. The experimental SAH was induced by injecting autologous blood into the cisterna magna of the rabbit. Experiments were performed on the following three groups: (a) SAH group with nitroglycerin tape (nitroglycerin group), (b) SAH group with placebo tape (placebo group), and (c) saline group injected with saline instead of blood. The tape containing 0.675 mg nitroglycerin was applied once daily for 2 days onto the skin area of the rabbit's ear. Angiograms were performed once before cisternal injection of blood and/or saline and again on day 2. On day 2 the basilar artery was isolated and sliced into 2-mm ring preparations. Relaxations of the basilar artery to acetylcholine, sodium nitroprusside, and calcium ionophore A23187, as well as the contractile responses to serotonin and endothelin-l, were measured. The diameter of the basilar artery on day 2 was reduced to 69.6 +/- 2.2% (n = 7) before the injection of autologous blood. The angiographic vasospasm of the basilar artery was partially but significantly (p &lt; 0.0001) improved to the percentage diameter of 89.4 +/- 1.4% (n = 7) by the application of low-dose nitroglycerin, which did not affect the systemic blood pressure and heart rate. In the basilar artery preparations harvested from SAH rabbits on day 2, the impaired acetylcholine-induced endothelium-dependent relaxation was partially but significantly (p &lt; 0.001) improved in the nitroglycerin group However, this group remained unaffected in the increased sensitivity to nitroglycerin and the contractile responses to serotonin and endothelin-l. Low-dose nitroglycerin tape effectively improved the cerebral vasospasm after SAH without any significant changes in the systemic circulation and would be one of the useful and noninvasive treatments for cerebral vasospasm. The results seem to be partially affected by the effective dilation of the spastic artery and the improvement of the impaired endothelium-dependent relaxation with low-dose NO.

DOI： 10.1097/00005344-200001000-00006

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Language：Japanese   Publisher：スパズム・シンポジウム事務局  

低用量NTG・塩酸ファスジル併用療法によってウサギくも膜下出血モデルにおける脳血管攣縮は完全に予防し得た.予防的薬物療法には内因性NOと同様のパラクリン作用を有するNO donorが望ましい

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We previously demonstrated that L-DOPA modulated the vascular α1-adrenergic receptor through GPR143, a G-protein coupled receptor, and sensitized vasomotor tone. In this study, we examined a possible role of GPR143 in the pathogeneisis of pulmonary hypertension (PH). In isolated pulmonary arteries, L-DOPA (1 μM) augmented contractile response to phenylephrine, an α1 adrenergic receptor agonist. We generated GPR143 gene-deficient (<i>Gpr143</i>^<i>-/y</i>) rats and comparatively studied the effect of L-DOPA. L-DOPA did not modify phenylephrine-induced response in the pulmonary arteries of <i>Gpr143</i>^<i>-/y</i> rats, thereby indicating that the action of L-DOPA was mediated by GPR143. We next established monocrotaline (MCT, 60 mg/kg) -induced PH model in wild type (WT) and <i>Gpr143</i>^<i>-/y</i> rats. One month after injection subcutaneously with MCT , the right ventricular systolic pressure (RVSP) was attenuated in <i>Gpr143</i>^<i>-/y</i> rats as compared to the WT rats (49.7 +/- 1.1 mmHg and 41.4 +/- 1.4 mmHg in WT and <i>Gpr143</i>^<i>-/y</i>, p&lt;0.05, N=5). Coordinately, the right ventricle to body weight (RV/BW) (5.4 +/- 0.2 × 10^-4 and 4.7 +/- 0.1 × 10^-4 in WT and <i>Gpr143</i>^<i>-/y</i>, p&lt;0.01, N=12) was also reduced in <i>Gpr143</i>^<i>-/y</i> rats compared to the WT rats. Furthermore, in primary cultures of pulmonary artery smooth muscle cells (PASMCs), the proliferative and migratory capacity of <i>Gpr143</i>^<i>-/y</i> PASMCs after phenylephrine treatment was reduced compared to <i>Gpr143</i>-WT PASMCs. We here provide evidence that GPR143 may be involved in MCT-induced PH in rats by affecting the proliferative and migratory capacity of PASMCs.

DOI： 10.1254/jpssuppl.95.0_1-yia-06

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Language：Japanese   Publisher：克誠堂出版(株)  

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症例は64歳女性で、左外上部乳がんの診断で約半年前から術前化学療法を受け、乳房部分切除術および腋窩リンパ節生検を予定された。間質性肺炎再燃のリスクを考慮し、全身麻酔を避けpectoral nerve blockブロックのみで麻酔管理する方針とした。ブロックは仰臥位で、リニアプローブと22G Tuohy針を用いて超音波ガイド下に第4肋骨上、大胸筋と前鋸筋の間に0.25%レボブピバカインを40ml投与し、さらに傍胸骨で大胸筋全面に0.25%レボブピバカインを15ml投与した。術中は腋窩の最も背側の部分で疼痛を認め、1%リドカイン1mlの局所浸潤麻酔を要したが、その他は問題なく手術は予定どおり終了した。予術終了後の経過観察で、間質性肺炎の増悪を疑う症状および検査所見は認めなかった。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2018&ichushi_jid=J01397&link_issn=&doc_id=20180608080010&doc_link_id=%2Fad3msuie%2F2018%2F006706%2F011%2F0611-0613%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fad3msuie%2F2018%2F006706%2F011%2F0611-0613%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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82歳女。74歳時に筋萎縮性側索硬化症(ALS)と診断され、嚥下障害の進行により誤嚥性肺炎を繰り返すようになり、内視鏡的胃瘻造設術が予定された。しかし、局所麻酔下での手術中に胃穿孔を偶発し、緊急開腹術に移行することとなった。重度の呼吸機能障害を呈するALS患者であったことから、硬膜外麻酔を選択しNPPVを併用したところ、安全に麻酔管理を行うことが可能であった。

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15歳男性。突然の頭痛と嘔吐により著者らの施設へ救急搬送され、頭部CTにてクモ膜下出血と診断後、入院となった。所見ではほかに聴診上、前胸部に収縮期雑音が聴取され、心電図では左室肥大が認められた。また、両上肢での血圧測定では血圧値の左右差が認められた。そのため脳血管造影とあわせて大動脈造影を行ったところ、脳血管造影では前大脳動脈瘤がみられ、大動脈造影では左鎖骨下動脈分岐部の狭窄が認められた。以上より、本症例は大動脈縮窄とそれに伴う脳動脈瘤破裂と診断され、全身麻酔下に開頭クリッピング術が施行された。術中は左鎖骨下動脈分岐部の大動脈狭窄による上肢血圧の左右差があったことから、右橈骨動脈の観血的動脈圧と左橈骨動脈の観血的動脈圧を測定し、更に左大腿でも非観血的動脈圧を測定した。その結果、左橈骨動脈の平均血圧と左大腿での平均血圧はほぼ等しい値となり、患者は術後経過良好で、入院20日後には独歩退院となった。

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Event date： 2018

Language：English  

Background: We previously reported a tele-anesthesia system that connected Sado General Hospital (SGH) to Yokohama City University Hospital (YCUH) using a dedicated virtual private network (VPN) that guaranteed the quality of service. The study indicated certain unresolved problems, such as the high cost of constantly using a dedicated VPN for tele-anesthesia. In this study, we assessed whether use of a best-effort system affects the safety and cost of tele-anesthesia in a clinical setting. Methods: One hundred patients were enrolled in this study. We provided tele-anesthesia for 65 patients using a guaranteed transmission system (20 Mbit/s; guaranteed, 372,000 JPY per month: 1 JPY = US$0.01) and for 35 patients using a best-effort system (100 Mbit/s; not guaranteed, 25,000 JPY per month). We measured transmission speed and number of commands completed from YCUH to SGH during tele-anesthesia with both transmission systems. Results: In the guaranteed system, anesthesia duration was 5780 min (88.9 min/case) and surgical duration was 3513 min (54.0 min/case). In the best-effort system, anesthesia duration was 3725 min (106.4 min/case) and surgical duration was 2105 min (60.1 min/case). The average transmission speed in the best-effort system was 17.3 ± 3.8 Mbit/s. The system provided an acceptable delay time and frame rate in clinical use. All commands were completed, and no adverse events occurred with both systems. Discussion: In the field of tele-anesthesia, using a best-effort internet VPN system provided equivalent safety and efficacy at a better price as compared to using a guaranteed internet VPN system.

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Event date： 2016.4

Language：English  

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Event date： 2015.3

Language：English  

We studied the use of tele-anaesthesia between Sado General Hospital (SGH) located on Sado Island and Yokohama City University Hospital (YCUH) located in mainland Japan. The two sites were connected via a virtual private network (VPN). We investigated the relationship between the bandwidth of the VPN and both the frame rate and the delay time of the tele-anaesthesia monitoring system. The tool used for communication between the two hospitals was free videoconferencing software (FaceTime), which can be used over Wi-Fi connections. We also investigated the accuracy of the commands given during teleanaesthesia: any commands from the anaesthetist at the YCUH that were not carried out for any reason, were recorded in the anaesthetic records at the SGH. The original frame rate and data rate at the SGH were 5fps and approximately 18 Mbit/s, respectively. The frame rate at the transmission speeds of 1, 5 and 20 Mbit/s was 0.6, 1.6 and 5.0fps, respectively. The corresponding delay time was 12.2, 4.9 and 0.7s. Twenty-five adult patients were enrolled in the study and tele-anaesthesia was performed. The total duration of anaesthesia was 37 hours. All 888 anaesthetic commands were completed. There were 7 FaceTime disconnections, which lasted for 10min altogether. Because no commands needed to be given during the FaceTime disconnection, the telephone was not used. The anaesthesia assistance system might form part of the solution to medical resource shortages.

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Event date： 2014.11

Language：English  

Children with complex congenital heart diseases often require repeated cardiac catheterization; however, children are more radiosensitive than adults. Therefore, radiation-induced carcinogenesis is an important consideration for children who undergo those procedures. We measured entrance skin doses (ESDs) using radio-photoluminescence dosimeter (RPLD) chips during cardiac catheterization for 15 pediatric patients (median age, 1.92 years; males, n = 9; females, n = 6) with cardiac diseases. Four RPLD chips were placed on the patient's posterior and right side of the chest. Correlations between maximum ESD and dose-area products (DAP), total number of frames, total fluoroscopic time, number of cine runs, cumulative dose at the interventional reference point (IRP), body weight, chest thickness, and height were analyzed. The maximum ESD was 80 +/- 59 (mean +/- standard deviation) mGy. Maximum ESD closely correlated with both DAP (r = 0.78) and cumulative dose at the IRP (r = 0.82). Maximum ESD for coiling and ballooning tended to be higher than that for ablation, balloon atrial septostomy, and diagnostic procedures. In conclusion, we directly measured ESD using RPLD chips and found that maximum ESD could be estimated in real-time using angiographic parameters, such as DAP and cumulative dose at the IRP. Children requiring repeated catheterizations would be exposed to high radiation levels throughout their lives, although treatment influences radiation dose. Therefore, the radiation dose associated with individual cardiac catheterizations should be analyzed, and the effects of radiation throughout the lives of such patients should be followed.

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Event date： 2014.8

Language：English  

Pulmonary hypertension (PH) is associated with significant morbidity and mortality. Vasoactive intestinal peptide (VIP) and pituitary adenylyl cyclase activating peptide (PACAP) have pulmonary vasodilatory and positive inotropic effects via receptors VPAC1 and VPAC2, which possess a similar affinity for both peptides, and PAC1, a PACAP-preferring receptor. VIP is a promising option for PH treatment; however, various physiological effects of VIP have limited its clinical use. We investigated the effects of VPAC1 and VPAC2 selective agonists VIP and PACAP to explore more appropriate means of treatment for PH. We examined hemodynamic changes in right ventricular systolic pressure (RVSP), systemic blood pressure (SBP), total pulmonary resistance index (TPRI), total systemic resistance index, and cardiac index (CI) in response to their agonists with monocrotaline (MCT)-induced PH and explored involvement of VIP/PACAP expression and receptors in PH. Sprague-Dawley rats were divided into the MCT group (administered MCT 60 mg/kg) and control group. In MCT-induced PH, decreased VIP and PACAP were associated with upregulation of VPAC1, VPAC2, and PAC1 in lung tissues. Intravenous injection of VPAC2-selective agonist BAY 55-9837 and VIP, but not [Ala(11,22,28)] VIP, improved the CI. The decrease in SBP with VPAC2 agonist was significantly less than that in the control. Although they decreased SBP, these agonists hardly affected RVSP in the control. Activation of VPAC2 receptor with BAY 55-9837 effectively improved RVSP, TPRI, and CI in MCT-induced PH, suggesting a VPAC2 agonist as a possible promising treatment for PH.

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Event date： 2013.4

Language：English  

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Event date： 2013

Language：English  

BACKGROUND: An unintended bolus is delivered by the syringe pump if intravenous line occlusion is released in an inappropriate manner.
OBJECTIVE: The aim of this study was to measure the amount of flushed fluid when an occlusion is inappropriately released and to assess the effect of different syringe pump settings (flow rate, alarm setting, size of syringe and syringe pump model) on the flushed amount.
METHODS: After the stopcock was closed, infusions were started with different model syringe pumps (Terufusion (R) TE312 and TE332S), different syringe sizes or at different alarm settings. After the occlusion alarm sounded, the occlusion was released and the amount of fluid emerging from the stopcock was measured.
RESULTS: The bolus was significantly lower when the alarm was set at a low-pressure setting. The bolus was significantly lower with a 10-ml than a 50-ml syringe. A significant difference was seen only when a 50-ml syringe was used (TE312: 1.99 +/- 0.16 ml vs. TE332S: 0.674 +/- 0.116 ml, alarm High, p &lt; 0.001).
CONCLUSION: To minimize the amount of accidentally injected medication, a smaller syringe size and a low alarm setting are important. Using a syringe pump capable of reducing the inadvertently administered bolus may be helpful.

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Event date： 2011.12

Language：English  

Although several cases of radiation-induced skin injury (RSI) have been reported in association with neurointerventional procedures, such as endovascular embolization for cerebral aneurysm, the absorbed doses are not directly measured in most cases. We therefore built a direct measurement system in order to simplify determination of the entrance skin dose (ESD) during neurointerventional procedures. This system was then applied to patients undergoing long and repetitive procedures in order to establish the efficacy of precise mapping of ESDs using a number of radiophotoluminescence glass dosimeters (RPLDs) and to avoid RSI. We also analyzed the correlation between maximum ESDs and angiographic parameters in order to estimate maximum ESD in real-time.
ESD was measured in 35 procedures in 34 cerebral aneurysm patients with a median age of 65 years (range, 38-79 years). Patients were measured for ESDs while wearing a fitted dosimetry cap equipped with 60 RPLD chips throughout the procedure. Angiographic parameters, including total fluoroscopic time and dose-area product (DAP), were recorded. The Pearson correlation test was used to determine the relationship between maximum ESD and each parameter.
Five of thirty-five procedures showed temporal epilation (14.3%). The correlations between a patient's maximum ESD and total fluoroscopic time and DAP were r = 0.7372, P &lt; 0.001 and r = 0.6698, P &lt; .001, respectively.
We concluded that the regional ESD with geometric information could be obtained by applying the RPLDs. Although this passive dosimetry system may not entirely prevent RSI in real-time, precise dose mapping accompanied by monitoring of angiographic parameters during the procedure should contribute to reducing X-ray dose accumulation in repeated prophylactic endovascular embolization for asymptomatic cerebral aneurysm. (C) 2011 Elsevier Ltd. All rights reserved.

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Event date： 2008.8

Language：English  

Ca2+/calmodulin (CaM)-dependent phosphorylation of myosin regulatory light chain (RLC) in smooth muscle by myosin light chain kinase (MLCK) and dephosphorylation by myosin light chain phosphatase (MLCP) are subject to modulatory cascades that influence the sensitivity of RLC phosphorylation and hence contraction to intracellular Ca2+ concentration ([Ca2+](i)). We designed a CaM-sensor MLCK containing smooth muscle MLCK fused to two fluorescent proteins linked by the MLCK CaM-binding sequence to measure kinase activation in vivo and expressed it specifically in mouse smooth muscle. In phasic bladder muscle, there was greater RLC phosphorylation and force relative to MLCK activation and [Ca2+](i) with carbachol (CCh) compared with KCl treatment, consistent with agonist-dependent inhibition of MLCP. The dependence of force on MLCK activity was nonlinear such that at higher concentrations of CCh, force increased with no change in the net 20% activation of MLCK. A significant but smaller amount of MLCK activation was found during the sustained contractile phase. MLCP inhibition may occur through RhoA/Rho-kinase and/or PKC with phosphorylation of myosin phosphatase targeting subunit-1 (MYPT1) and PKC-potentiated phosphatase inhibitor (CPI-17), respectively. CCh treatment, but not KCl, resulted in MYPT1 and CPI-17 phosphorylation. Both Y27632 (Rho-kinase inhibitor) and calphostin C ( PKC inhibitor) reduced CCh-dependent force, RLC phosphorylation, and phosphorylation of MYPT1 (Thr694) without changing MLCK activation. Calphostin C, but not Y27632, also reduced CCh-induced phosphorylation of CPI-17. CCh concentration responses showed that phosphorylation of CPI-17 was more sensitive than MYPT1. Thus the onset of agonist-induced contraction in phasic smooth muscle results from the rapid and coordinated activation of MLCK with hierarchical inhibition of MLCP by CPI-17 and MYPT1 phosphorylation.

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Event date： 2008.1

Language：English  

We designed the present experiments to investigate the involvement of endogenous nitric oxide synthase (NOS) inhibitors, dimethylarginine dimethylaminohydrolase (DDAB) as a hydrolyzing enzyme of the NOS inhibitors, NOS, arginase which shares L-arginine as a common substrate with NOS, and endothelin-1 (ET-1) in the pulmonary dysfunction after induction of experimental subarachnoid hemorrhage (SAH) in the rabbit. SAH was induced by injecting autologous blood into the cisterna magna, and controls were injected with saline. On day 2, pulmonary arteries were isolated for determinations. A significant impairment of the endothelium-dependent relaxation (EDR) caused by acetylcholine was found in 20 cases (43.5%) out of 46 SAH animals, and the same animals exhibited accompanying the significantly impaired cyclic GMP production, accumulated endogenous NOS inhibitors, attenuated DDAH activity, enhanced arginase activity and accumulated ET-1 within the vessel wall. Meanwhile, there were no differences in endothelial NOS activity per se and sodium nitroprusside-induced relaxation between the animals with an impaired EDR and those without such a change. ET-1 content within aortic wall was increased with concomitant decrease in cyclic GMP production after the intraperitoneal application of authentic monomethylarginine as a NOS inhibitor in the rat. The current results suggest that accumulated endogenous NOS inhibitors and enhanced arginase activity possibly bring about the impaired NO production, thereby attenuating the EDR and contributing to the accumulation of ET-1 within the vessel wall. The accumulated endogenous NOS inhibitors at least partly result from the decreased DDAH activity. These alterations may be relevant to the pulmonary dysfunction after induction of SAH. (C) 2007 Elsevier Inc. All rights reserved.

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Event date： 2007.8

Language：English  

The present study was designed to investigate whether endothelial intracellular calcium concentration ([Ca2+](i)), endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) generation altered in association with impaired endothelium-dependent relaxation (EDR) in pulmonary artery (PA) specimens from experimental subarachnoid hemorrhage (SAH) rabbits. Injecting non-heparinized autologous arterial blood into cisterna magna induced the SAH. Simultaneous measurements of enclotbelial [Ca2+](i) and isometric tension of PA specimens were performed using fura 2. The subjects included normal control rabbits (group N), SAH rabbits with normal EDR (group A) and with impaired EDR (group B). When treated with 10(-7) M acetylcholine (ACh), endothelial [Ca2+](i) was significantly lower in group B (74.1 +/- 8.5 nM) than that in groups A (153.0 +/- 28.0 nM, p &lt; 0.05) and N (184.8 +/- 27.8 nM, p &lt; 0.01). Basal and ACh-stimulated cyclic GMP productions as a marker of NO generation were also significantly (p &lt; 0.005) decreased in group B as compared to those in the other two groups. Meanwhile, there were no differences in eNOS activity per se among the three groups. These results suggest that the attenuated endothelial [Ca2+](i) elevation leads to the impaired NO generation in PA endothelium, which in turn impairs the EDR and possibly increases the vascular resistance of PA following SAH. (C) 2007 Published by Elsevier Inc.

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Event date： 2007.5

Language：English  

Excitation-contraction (E-C) coupling and Ca2+-induced Ca2+ release in smooth and cardiac muscles is mediated by the L-type Ca2+ channel isoform Ca(v)1.2 and the ryanodine receptor isoform RyR2. Although physical coupling between Ca(v)1.1 and RyR1 in skeletal muscle is well established, it is generally assumed that Ca(v)1.2 and RyR2 do not directly communicate either passively or dynamically during E-C coupling. In the present work, we re-examined this assumption by studying E-C coupling in the detrusor muscle of wild type and Homer1(-/-) mice and by demonstrating a Homer1-mediated dynamic interaction between Ca(v)1.2 and RyR2 using the split green fluorescent protein technique. Deletion of Homer1 in mice (but not of Homer2 or Homer3) resulted in impaired urinary bladder function, which was associated with higher sensitivity of the detrusor muscle to muscarinic stimulation and membrane depolarization. This was not due to an altered expression or function of RyR2 and Ca(v)1.2. Most notably, expression of Ca(v)1.2 and RyR2 tagged with the complementary C- and N- terminal halves of green fluorescent protein and in the presence and absence of Homer1 isoforms revealed that H1a and H1b/c reciprocally modulates a dynamic interaction between Ca(v)1.2 and RyR2 to regulate the intensity of Ca2+-induced Ca2+ release and its dependence on membrane depolarization. These findings define the molecular basis of a "two-state" model of E-C coupling by Ca(v)1.2 and RyR2. In one state, Ca(v)1.2 couples to RyR2 by H1b/c, which results in reduced responsiveness to membrane depolarization and in the other state H1a uncouples Ca(v)1.2 and RyR2 to enhance responsiveness to membrane depolarization. These findings reveal an unexpected and novel mode of interaction and communication between Ca(v)1.2 and RyR2 with important implications for the regulation of smooth and possibly cardiac muscle E-C coupling.

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Event date： 2006.1

Language：English  

Disruption of protein synthesis and folding results in ER stress, which is associated with the pathophysiology of diverse diseases affecting secretory and muscle cells. Cells are protected against ER stress by activation of the unfolded protein response (UPR) that is regulated by the protein kinase PERK, which phosphorylates the translation initiation factor 2 eIF2 alpha to attenuate protein synthesis. PERK-/- cells are unable to modulate ER protein load and experience high levels of ER stress. In addition to its role in protein synthesis, the ER also orchestrates many signaling events essential for cell survival, prominent among which is Ca2+ signaling. It is not known, however, whether there is a relationship between ER stress and the function of the Ca2+ signaling pathway in muscle and nonmuscle cells. To directly address this question we characterized Ca2+ signaling in the secretory pancreatic and parotid acinar cells and in urinary bladder smooth muscle (UBSM) cells obtained from PERK-/- and wild-type mice. Deletion of PERK that results in high levels of ER stress, and distention and fragmentation of the ER slowed the rate of agonist-mediated Ca2+ release from the ER and reduced Ca2+-induced Ca2+ release, although IP3 production, localization of the IP3 receptors, IP3-mediated Ca2+ release, Ca(v)1.2 current and RyRs activity remained unaltered. On the other hand, ER stress disrupted the integrity of the Ca2+-signaling complexes in both secretory and UBSM cells, as revealed by markedly reduced coimmunoprecipitation of plasma membrane- and ER-resident Ca2+-signaling proteins. These findings establish a relationship between the unfolding protein response, ER stress and Ca2+ signaling and highlight the importance of communication within the terminal ER-plasma membrane microdomain for propagation of the Ca2+ signal from the plasma membrane into the cell.

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Event date： 2005.3

Language：English  

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Event date： 2004.4

Language：English  

Ca2+/calmodulin (CaM)-dependent phosphorylation of myosin regulatory light chain (RLC) by myosin light chain kinase (MLCK) initiates smooth muscle contraction and regulates actomyosin-based cytoskeletal functions in nonmuscle cells. The net extent of RLC phosphorylation is controlled by MLCK activity relative to myosin light chain phosphatase activity. We have constructed a CaM-sensor MLCK where Ca2+-dependent CaM binding increases the catalytic activity of the kinase domain, whereas coincident binding to the biosensor domain decreases fluorescence resonance energy transfer between two fluorescent proteins. We have created transgenic mice expressing this construct specifically in smooth muscle cells to perform real-time evaluations of the relationship between smooth muscle contractility and MLCK activation in intact tissues and organs. Measurements in intact bladder smooth muscle demonstrate that MLCK activation increases rapidly during KCl-incluced contractions but is not maximal, consistent with a limiting amount of cellular CaM. Carbachol treatment produces the same amount of force development and RLC phosphorylation, with much smaller increases in [Ca2+](i) and MLCK activation. A Rho kinase inhibitor suppresses RLC phosphorylation and force but not MLCK activation in carbachol-treated tissues. These observations are consistent with a model in which the magnitude of an agonist-mediated smooth muscle contraction depends on a rapid but limited Ca2+/CaM-dependent activation of MLCK and Rho kinase-mediated inhibition of myosin light chain phosphatase activity. These studies demonstrate the feasibility of producing transgenic biosensor mice for investigations of signaling processes in intact systems.

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Event date： 2002.5

Language：English  

This study investigated whether activated protein C (APC) improves the cerebral vasospasm in an experimental subarachnoid hemorrhage that was produced by the intracisternal injection of autologous blood. Male rabbits were divided into the following four groups: APC 0.1- and 0.5-mg groups, in which 0.1 and 0.5 mg APC were injected into the cisterna magna, respectively; a placebo group, in which saline was injected instead of APC; and a sham operation group that did not get injections of autologous blood, APC, and saline. On day 2, amount of clot in the basal cistern was significantly (p &lt; 0.01) decreased in the APC 0.5-mg group. Percent diameter of the basilar artery on day 2 to that before injecting the blood was angiographically determined as 97.1 +/- 3.8% in the APC 0.5-mg group, which was significantly (p &lt; 0.001) greater than the corresponding value in the placebo group (74.8 +/- 3.4%). The impaired endothelium-dependent relaxation following subarachnoid hemorrhage was normalized in the APC 0.5-mg group (p &lt; 0.0001). These results suggest that APC would improve cerebral vasospasm following subarachnoid hemorrhage, possibly by decreasing the amount of subarachnoid clot and normalizing the impaired nitric oxide production/release.

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Event date： 2000.1

Language：English  

In the rabbit subarachnoid hemorrhage (SAH) model, the sensitivity of spastic basilar arteries to nitric oxide (NO) was enhanced whereas the endothelial function to release/ produce NO became impaired, as described previously. We assumed from these results that low-dose NO might selectively dilate spastic arteries without influencing normal or systemic blood vessels; therefore, we investigated whether exogenous low-dose NO effectively improves cerebral vasospasm. Low-dose NO was derived from a small size of the tape containing nitroglycerin, which is not invasive and is clinically available. The experimental SAH was induced by injecting autologous blood into the cisterna magna of the rabbit. Experiments were performed on the following three groups: (a) SAH group with nitroglycerin tape (nitroglycerin group), (b) SAH group with placebo tape (placebo group), and (c) saline group injected with saline instead of blood. The tape containing 0.675 mg nitroglycerin was applied once daily for 2 days onto the skin area of the rabbit's ear. Angiograms were performed once before cisternal injection of blood and/or saline and again on day 2. On day 2 the basilar artery was isolated and sliced into 2-mm ring preparations. Relaxations of the basilar artery to acetylcholine, sodium nitroprusside, and calcium ionophore A23187, as well as the contractile responses to serotonin and endothelin-l, were measured. The diameter of the basilar artery on day 2 was reduced to 69.6 +/- 2.2% (n = 7) before the injection of autologous blood. The angiographic vasospasm of the basilar artery was partially but significantly (p &lt; 0.0001) improved to the percentage diameter of 89.4 +/- 1.4% (n = 7) by the application of low-dose nitroglycerin, which did not affect the systemic blood pressure and heart rate. In the basilar artery preparations harvested from SAH rabbits on day 2, the impaired acetylcholine-induced endothelium-dependent relaxation was partially but significantly (p &lt; 0.001) improved in the nitroglycerin group However, this group remained unaffected in the increased sensitivity to nitroglycerin and the contractile responses to serotonin and endothelin-l. Low-dose nitroglycerin tape effectively improved the cerebral vasospasm after SAH without any significant changes in the systemic circulation and would be one of the useful and noninvasive treatments for cerebral vasospasm. The results seem to be partially affected by the effective dilation of the spastic artery and the improvement of the impaired endothelium-dependent relaxation with low-dose NO.

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