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

背景与目的：为了了解麻醉相关药物对脑微循环的影响机制，研究了局部应用k通道打开剂（尼可地尔）、局麻药（可卡因）、内皮素、α肾上腺素能激动剂（地塞米托咪定）对脑血管舒缩张力的药理学反应。方法：将戊巴比妥轻度麻醉的狗、猫，在顶骨颅窗下应用溶解于人工脑脊液中的各种药物。在不同浓度的情况下，用带电视的显微镜测量头动脉和静脉的直径。在获得每种药物的效果后，对已知的拮抗剂进行预处理，然后给药并跟踪测量。结果：可卡因（10^<-4>-10^<-8>）和尼可地尔（10^<-3>-10^<-7>）呈剂量相关，其作用分别被心得安和亚甲基蓝预处理阻断。右美托咪定（10^<-4>-10^<-7>）以剂量相关的方式产生上动脉血管收缩，育亨宾完全阻断了这种作用。经腰蛛网膜下腔注射后，脊髓血流量明显减少，但脑血流量无明显减少。脊髓血流减少可部分拮抗尼卡地平。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外周血管研究的反应相似，因此作用机制可能相似，但敏感性有一定差异。

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.