SPINAL CORD BLOOD FLOW AND METABOLISM DURING ANESTHESIA

鉴于鞘内给药作为一种手段的兴趣与日俱增 对人类疼痛的调节，以及缺乏关于如何 此程序影响脊髓，此应用建议研究 对局部脊髓血流量(SCBF)和代谢的影响 鞘内注射局麻药、阿片类药物和肾上腺素能 激动剂。 雄性Spraogue-Dawley大鼠将准备好腰椎蛛网膜下腔 24-48小时后置入股动脉和静脉导管。 此后，实验将在有意识的情况下进行，部分 受束缚的大鼠；一般生理状态将通过动脉评估 血压、血气和酸碱度，以及体温测量。 实验动物将在鞘内注射10-15微升的生理盐水 以防止传播到脊椎上区域；对照动物将收到 只有生理盐水。将药物以止痛剂的剂量和效果给予 通过甩尾反应的延迟来衡量。须接受检查的代理人 包括物理化学上不同局部麻醉剂；不同的阿片类药物 效力、脂类溶解度、受体亲和力或选择性；选择性和 非选择性α-肾上腺素能激动剂；以及 上面。在阳性结果的情况下，额外的试验旨在 从药理上拮抗SCBF效应或将其与 将进行止痛。将测量局部SCBF和/或新陈代谢 定量放射自显影在镇痛期的应用 碘-(14C)安替比林法和2-(14C)脱氧葡萄糖法。 这些研究将提供有关脊髓的基本新信息。 鞘内镇痛期间的循环和代谢生理学，并可能 帮助解释药物摄取和消除的各个方面 蛛网膜下腔。这些研究还可能为我们深入了解 内源性神经递质在SCBF及代谢调节中的作用 生理和病理生理条件，并可能有助于预测或 解释偶尔出现的用药对神经系统的不良影响 直接进入神经轴。

In view of growing interest in intrathecal drug administration as a means of modulating pain in humans and the lack of information pertaining to how this procedure affects the spinal cord, this application proposes studies of the local spinal cord blood flow (SCBF) and metabolic effects of intrathecally administered local anesthetics, opiates, and adrenergic agonists. Male, Sprague-Dawley rats will be prepared with a lumbar subarachnoid catheter and, 24-48 h later, femoral artery and vein catheters. Thereafter, experiments will be conducted in conscious, partially restrained rats; general physiologic state will be evaluated by arterial blood pressure, blood gas and pH, and temperature measurement. Experimental animals will receive drugs intrathecally in 10-15 ul of saline so as to prevent spread to supraspinal areas; control animals will receive only saline. Drugs will be administered in analgesic doses and the effect measured by latency of the tail-flick response. Agents to be examined include physiochemically different local anesthetics; opiates of different potency, lipid solubility, receptor affinity, or selectivity; selective and non-selective alpha adrenergic agonists; and some combinations of the above. In cases of positive results, additional experiments designed to pharmacologically antagonize the SCBF effect or dissociate it from analgesia will be performed. Local SCBF and/or metabolism will be measured during the period of analgesia with the quantitative, autoradiographic iodo-(14C)antipyrine and 2-(14C)deoxyglucose methods, respectively. These studies will provide basic, new information on spinal cord circulatory and metabolic physiology during intrathecal analgesia, and may help explain aspects of uptake and elimination of drugs from the subarachnoid space. The studies may also provide insight into the role of endogenous neurotransmitters in the regulation of SCBF and metabolism under physiologic and pathophysiologic conditions, and, possibly, help predict or explain the occasional untoward neurologic effects of administering drugs directly into the neuraxis.