ANESTHETIC PROTECTION IN BRAIN HYPOXIA: A P31 NMR STUDY

脑缺氧时的麻醉保护：P31 NMR 研究

• 批准号: 3447882
• 负责人: Lawrence Litt
• 金额: $ 3.6万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1988-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3447882
• 关键词: acid base balance; adenosine triphosphate; anesthetics; brain disorder diagnosis; brain electrical activity; brain imaging /visualization /scanning; brain metabolism; cerebral ischemia /hypoxia; creatine phosphate; fentanyl; free fatty acids; glucose metabolism; halothane; high performance liquid chromatography; hypoxia; ketamine; lactates; nuclear magnetic resonance spectroscopy; phosphates; respiratory therapy; thiopental

We propose an in vivo study of hypoxic and ischemic brain injury in anesthesized rats with 31P and 1H NMR spectroscopy. Our aim is to evaluate factors that predict and contribute to cerebral damage, and to compare the metabolic protection conferred by thiopental, isoflurane, halothane, and fentanyl. Ketamine, an anesthetic that does not protect the brain, will be studied and compared with the other agents. Four basic questions will be addressed: 1) How do the different anesthetic agents ameliorate hypoxic and ischemic brain injury? 2) How soon can in vivo NMR spectroscopy determine that irreversible injury has occurred? 3) Does hypoxia during anesthesia produce more injury than global ischemia? 4) When hypoxic and ischemic brain damage occur during anesthesia, how much injury during reperfusion? Our study will use a horizontal NMR spectrometer whose magnetic field strength is 5.6 Tesla. Anesthetized rats will be placed prone in a region of high magnetic field homogeneity, and will be studied using a 14 mm low noise surface coil detector. 31P NMR spectroscopy will be performed in vivo during hyperoxia, hypoxic hypoxia, and global ischemia (obtained using Pulsinelli's model), and used to determine intracellular pH and intracellular concentrations of ATP, PCr, Pi, and monophosphate sugars. 1H spectroscopy will be performed separately under similar conditions to study intracellular concentrations of lactate and N-acetylaspartate. Magnetization transfer methods will be used to measure the unidirectional fluxes and unidirectional rate constants for the creatine kinase (CPK) and ATP synthetase reactions. Deterioration and recovery of energy stores will be studied during hypoxia and ischemia, and correlated with invasive post-mortem measurments of membrane phospholipids and free fatty acids, done by collaborators using freeze extraction techniques and HPLC. In vitro studies indicate that metabolic and electrical activity can return to normal in CNS neurons that were deprived of oxygen and glucose for 20 to 60 minutes. Clinical situations involving more than a few minutes of insufficient oxygen or glucose supply often result in permanent damage. We hope that our in vivo studies of different anesthetics will suggest therapeutic strategies for humans that extend the brain's tolerance of oxygen deprivation and reduce the likelihood of intraoperative brain injury.

我们提出了一项体内研究缺氧和缺血性脑损伤的体内研究 用31p和1H NMR光谱法麻醉大鼠。 我们的目标是评估 预测和造成大脑损害的因素，并比较 由硫代，异氟烷，卤素和 芬太尼。 氯胺酮是一种不保护大脑的麻醉剂，将是 研究并与其他代理人进行了比较。 四个基本问题将是 解决：1）不同的麻醉剂如何改善低氧 和缺血性的脑损伤？ 2）在多久内可以进行体内NMR光谱 确定发生不可逆伤害吗？ 3）在 麻醉会比全球性缺血更多？ 4）当缺氧和 麻醉期间发生缺血性脑损伤，在 再灌注？ 我们的研究将使用水平NMR光谱仪的磁场 力量为5.6特斯拉。 麻醉大鼠将俯卧在一个区域 高磁场同质性，并将使用14毫米低 噪声表面线圈探测器。 31p NMR光谱将在 高氧，缺氧缺氧和全局缺血期间的体内（使用 Pulsinelli的模型），用于确定细胞内pH和 ATP，PCR，PI和单磷酸糖的细胞内浓度。 1H 光谱法将在类似的条件下分别进行 乳酸和N-乙酰天冬氨酸的细胞内浓度。 磁化转移方法将用于测量单向 肌酸激酶（CPK）的通量和单向率常数和单向率常数 ATP合成酶反应。 能源存储的恶化和恢复将 在缺氧和缺血期间研究，并与侵入性相关 膜磷脂和游离脂肪酸的验尸测量， 由合作者使用冻结提取技术和HPLC完成。 体外研究表明代谢和电活动可以返回 在中枢神经系统神经元中被剥夺氧气和葡萄糖20至20 60分钟。 涉及超过几分钟的临床情况 氧气或葡萄糖供应不足通常会导致永久损害。 我们 希望我们对不同麻醉剂的体内研究会暗示 对人类的治疗策略，扩大大脑的耐受性 缺氧并减少术中脑损伤的可能性。