Mechanisms of Anesthesia-related drugs on Cerebral Microcirculation - A In Vivo Study Using Intravital Microscope

麻醉相关药物对脑微循环的影响机制——活体显微镜体内研究

基本信息

批准号：
02454350
负责人：
DOHI Shuji
金额：
$ 2.43万
依托单位：
Gifu University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

Background and Purpose: In order to know mechanisms of anesthesia related drugs' effects on cerebral microcirculation, the investigator studied pharmacological responses to topical application of K-channel opener(nicorandil), local anesthetic(cocaine), endotheline, alpha adrenergic agonist(dexamedetomidine) on vasomotor tone of pial vessel.Methods: In dogs and cats anesthetized lightly with pentobarbital and prepared with a parietal cranial window, each agent dissolved in artificial cerebrospinal fluid were applied under the window. The pial arteriolar and venular diameters were measured ateach concentration by a videomicrometer with television attached to a microscope. After effects of each drug were obtained, a known antagonist was pretreated and then the drug was administered and followed the measurements.Results: Cocaine (10^<-4>-10^<-8>) and nicorandil (10^<-3>-10^<-7>) produced pial arteriolar vasodilation in a dose related fashion, and the effects were blocked with the pretreatment of propranolol and methylene blue, respectively. Dexmedetomidine (10^<-4>-10^<-7>) produced pial arteriolar vasoconstriction in a dose related fashion and this effect was completely blocked with yohimbine. End theline administered into lumbar subarachnoid space caused significant decrease in spinal cord blood flow but not in cerebral blood flow. The decreased spinal cord blood flow was partially antagonized with nicardipine.Conclusion: The results of the present in vivo studies suggest that pharmacological responses of cerebral microcirculation to potential spinal agents were similar to the responses obtained in vitro study using with peripheral vessels, and thus mechanism(s) of the act ioncould be similar with some difference in sensitivity.

背景与目的：为了解麻醉相关药物对脑微循环影响的机制，研究者研究了K通道开放剂（尼可地尔）、局麻药（可卡因）、内皮素、α肾上腺素能激动剂（右美托咪定）局部应用的药理反应。方法：用戊巴比妥轻轻麻醉狗和猫，并用顶叶准备颅窗，将各药剂溶解在人工脑脊液中，涂于窗下。通过带有连接到显微镜的电视的视频测微计测量每个浓度下的软脑膜小动脉和小静脉直径。获得每种药物的效果后，对已知的拮抗剂进行预处理，然后给药并进行测量。结果：可卡因（10^<-4>-10^<-8>）和尼可地尔（10^<-3 >-10^<-7>)以剂量相关的方式产生软脑膜小动脉血管舒张，并且分别用普萘洛尔和亚甲蓝预处理来阻断该作用。右美托咪定(10^-4>-10^-7)以剂量相关的方式产生软脑膜小动脉血管收缩，并且这种作用被育亨宾完全阻断。将线末端注射到腰部蛛网膜下腔会导致脊髓血流量显着减少，但不会导致脑血流量显着减少。尼卡地平可以部分拮抗脊髓血流量的减少。结论：目前的体内研究结果表明，脑微循环对潜在脊髓药物的药理反应与体外研究中使用外周血管获得的反应相似，因此机制动作离子的 (s) 可能相似，但灵敏度有所不同。