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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.

背景和目的：为了解麻醉相关药物对脑微循环影响的机制，研究了局部应用钾通道开放剂的药理学反应（尼可地尔）、局部麻醉剂（可卡因）、内皮素、α肾上腺素能激动剂（右美托咪定）对软脑膜血管张力的影响。在用戊巴比妥轻度麻醉并准备顶骨颅骨窗的犬和猫中，将溶解在人工脑脊液中的每种试剂施加在窗下。用电视显微镜测量软脑膜微动脉和微静脉的直径。结果：考地尔（10^<-4>-10 ^<-8>）和尼可地尔（10^<-3>-10 ^<-7>）对软脑膜小动脉的舒张作用呈剂量依赖性，普萘洛尔和亚甲蓝可阻断其作用。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，育亨宾可完全阻断该效应。尾静脉注入腰蛛网膜下腔可引起脊髓血流量明显减少，但对脑血流量无明显影响。结论：在体研究结果表明，潜在的脊髓药物对脑微循环的药理学反应与体外研究中使用外周血管获得的反应相似，因此作用机制可能相似，但敏感性有所不同。