RESEARCH OF THE MECHANISM OF GENEKRAL ANESTHESIA-ROLE OF P-GLYCOPROTEIN

全麻机制研究——P-糖蛋白的作用

基本信息

批准号：
14571460
负责人：
ODA Yutaka
金额：
$ 2.05万
依托单位：
Osaka City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571460/
关键词：
P-GLYCOPROTEIN OUINIDINE LIDOCAINE BUPIVACAINE LOCAL ANESTHETICS CONVULSIONS DEXMEDETOMIDINE

项目摘要

P-glycoprotein is expressed in endothelial cells in the blood brain barrier (BBB), intestinal mucosa and various other organs. P-glycoprotein expressed in BBB exports various compound administered extracorporeally. Intravenously administered local anesthetics are delivered to the central nervous system, promoting excitation and convulsion. Local anesthetics in the brain are also involved in the cardiovascular toxicity. For elucidating the role of P-glycoprotein for controlling convulsions by local anesthetics, we have developed an awake, spontaneously breathing rat model for observing convulsions.Male Sprague-Dawley rats aged 9-10 weeks and weighing 350-400g were housed 12 hour dark and light cycle. On the day of experiment, rat was anesthetized with inhalational sevoflurane in oxygen. Polyethylene catheters (PE-50 and SP-3) were inserted into carotid artery and cervical vein, respectively. After emergence from anesthesia, lidocaine was intravenously administered at 4 mg/kg/min under t … More he monitoring of blood pressure and heart rate until tonic/clonic convulsions occurred. At the onset of convulsions, rats were killed by intravenous administration of thiopental and the brain was perfused from the aorta. Blood sample was obtained from the indwelling arterial catheter and plasma and brain concentrations of lidocaine and its primary metabolite, monoethylglycinexylidide (MEGX) were measured. The same experimental protocol was used for measuring the convulsive potency of racemic bupivacaine (bupivacaine). Plasma concentrations of lidocaine and bupivacaine were measured according to our previous study. We have developed a new method for simple measurement of the concentration of local anesthetics in brain homogenates.Convulsant potency of lidocaine was not affected by pretreatment of a P-glycoprotein, quinidine. Convulsive dose and the concentration of bupivacaine in the brain were not changed by quinidine ; however, plasma concentration of bupivacaine at the onset of convulsinsions was significantly decreased by quinidine. These results suggest that P-glycoprotein is involved in controlling the concentration of bupivacaine, but not lidocaine, in the brain. Less

P-糖蛋白在血液屏障（BBB），肠粘膜和其他各种器官中的表达。麻醉药，我们开发了一种自发的，自发的大鼠大鼠模型，用于观察抽搐。在氧气中E Sprague-Dawley大鼠9-10周的9-10周大鼠且ige 350-400g的体验e 12小时。聚乙烯导管（PE-50和SP-3）分别插入颈动脉和颈静脉，在麻醉中出现后，利多卡因静脉内静脉注射4 mg/kg/minunder t ...插曲发生了，通过静脉内给予大脑的大鼠杀死大脑，从主动脉中灌注了lidocaine的脑子。日光外的布比卡因（Bupivivacaine）。在抽搐开始时，奎尼丁的素氨酸浓度没有改变，这些结果明显降低了这些结果