SPINAL CORD BLOOD FLOW AND METABOLISM DURING ANESTHESIA

麻醉期间的脊髓血流和代谢

• 批准号: 3278294
• 负责人: GREGORY CROSBY
• 金额: $ 11.44万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-05-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3278294
• 关键词: adrenergic agents; anesthetics; autoradiography; catheterization; clonidine; deoxyglucose; dosage; drug administration routes; drug metabolism; electrophysiology; evoked potentials; fentanyl; general anesthesia; local anesthetics; methoxamine; morphine; naloxone; narcotics; neuropharmacology; neurophysiology; opiate alkaloid; radiotracer; spinal cord

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.

鉴于对鞘内给药作为一种手段的兴趣日益增加， 调节人类疼痛的方法，以及缺乏关于如何调节疼痛的信息， 该手术影响脊髓，该申请提出了研究 局部脊髓血流量（SCBF）和代谢影响的 鞘内给药的局部麻醉剂、阿片类药物和肾上腺素能药物 激动剂 将制备雄性Sprague-Dawley大鼠的腰椎蛛网膜下腔， 导管，24-48小时后，股动脉和静脉导管。 此后，实验将在有意识的，部分 束缚大鼠;一般生理状态将通过动脉 血压、血气和pH以及温度测量。 实验动物将接受在10-15 μ l盐水中鞘内注射的药物 以防止扩散到脊髓上区域;对照动物将接受 只有盐水。 药物将以镇痛剂量给药， 通过甩尾反应的潜伏期来测量。 待检试剂 包括物理化学上不同局部麻醉剂;不同 效力、脂溶性、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;以及所述非选择性α肾上腺素能激动剂的一些组合。 以上 在阳性结果的情况下，额外的实验旨在 拮抗SCBF效应或将其与 将进行镇痛。 将测量局部SCBF和/或代谢 在镇痛期间，使用定量放射自显影 碘-（14 C）安替比林和2-（14 C）脱氧葡萄糖法。 这些研究将为脊髓提供基本的新信息 鞘内镇痛期间的循环和代谢生理学， 帮助解释药物的吸收和消除方面， 蛛网膜下腔 这些研究还可以深入了解 内源性神经递质在SCBF和代谢调节下 生理和病理生理条件，并可能有助于预测或 解释给药后偶尔出现的神经系统不良反应 直接刺入神经轴