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: 3447883
• 负责人: Lawrence Litt
• 金额: $ 4.45万
• 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/3447883
• 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.

我们建议在体内研究缺氧和缺血性脑损伤， 用31 P和1H NMR光谱法测定麻醉大鼠。 我们的目标是评估 预测和导致脑损伤的因素，并比较 硫喷妥钠、异氟烷、氟烷和 芬太尼 氯胺酮，一种不能保护大脑的麻醉剂， 研究并与其他药剂进行比较。 四个基本问题将是 研究内容：1）不同麻醉剂如何改善缺氧 和缺血性脑损伤 2)体内核磁共振光谱学 确定已经发生了不可逆的伤害？ 3)缺氧是否会在 麻醉比全脑缺血造成的损伤更大？ 4)当缺氧和 麻醉期间发生缺血性脑损伤， 再灌注？ 我们的研究将使用一个水平的核磁共振波谱仪， 强度为5.6特斯拉。 将麻醉的大鼠俯卧在一个区域 高磁场均匀性，并将使用14毫米低 噪声表面线圈探测器 31 P NMR光谱将在 在高氧、缺氧性低氧和全脑缺血期间体内（使用 Pulsinelli的模型），并用于测定细胞内pH和 ATP、PCr、Pi和单磷酸糖的细胞内浓度。 1H 将在类似的条件下单独进行光谱学研究 乳酸和N-乙酰天冬氨酸的细胞内浓度。 磁化传递方法将用于测量单向 肌酸激酶（CPK）的通量和单向速率常数， ATP合成酶反应。 能源储存的恶化和恢复将 在缺氧和缺血期间进行研究，并与侵袭性 死后测量膜磷脂和游离脂肪酸， 由合作者使用冷冻提取技术和HPLC完成。 体外研究表明，代谢和电活动可以恢复 正常的中枢神经系统神经元，被剥夺了氧气和葡萄糖20至 60分钟 临床情况涉及超过几分钟的 氧气或葡萄糖供应不足常常导致永久性损伤。 我们 我希望我们对不同麻醉剂的体内研究能表明， 为人类提供的治疗策略， 缺氧和减少术中脑损伤的可能性。

项目成果

Localized imaging using stimulated echoes.

使用受激回波进行局部成像。

• DOI: 10.1002/mrm.1910050412
• 发表时间: 1987
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Mills,P;Chew,W;Litt,L;Moseley,M
• 通讯作者: Moseley,M

Cerebral intracellular ADP concentrations during hypercarbia: an in vivo 31P nuclear magnetic resonance study in rats.

高碳酸血症期间脑细胞内 ADP 浓度：大鼠体内 31P 核磁共振研究。

• DOI: 10.1038/jcbfm.1986.64
• 发表时间: 1986
• 期刊: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
• 作者: Litt,L;Gonzalez-Mendez,R;Severinghaus,JW;Hamilton,WK;Rampil,IJ;Shuleshko,J;Murphy-Boesch,J;James,TL
• 通讯作者: James,TL

An in vivo study of halothane uptake and elimination in the rat brain with fluorine nuclear magnetic resonance spectroscopy.

用氟核磁共振波谱法研究大鼠脑中氟烷的吸收和消除。

• DOI: 10.1097/00000542-198708000-00002
• 发表时间: 1987
• 期刊: Anesthesiology
• 影响因子: 8.8
• 作者: Litt,L;González-Méndez,R;James,TL;Sessler,DI;Mills,P;Chew,W;Moseley,M;Pereira,B;Severinghaus,JW;Hamilton,WK
• 通讯作者: Hamilton,WK

An in vivo 19F nuclear magnetic resonance study of isoflurane elimination from the rabbit brain.

兔脑中异氟烷消除的体内 19F 核磁共振研究。

• DOI: 10.1097/00000542-198708000-00003
• 发表时间: 1987
• 期刊: Anesthesiology
• 影响因子: 8.8
• 作者: Mills,P;Sessler,DI;Moseley,M;Chew,W;Pereira,B;James,TL;Litt,L
• 通讯作者: Litt,L

An in vivo 31P NMR study of cerebral hypoxic hypoxia in rats.

大鼠脑缺氧缺氧的体内 31P NMR 研究。

• DOI: 10.1002/mrm.1910030414
• 发表时间: 1986
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Litt,L;González-Méndez,R;Weinstein,PR;Severinghaus,JW;Hamilton,WK;Shuleshko,J;Murphy-Boesch,J;James,TL
• 通讯作者: James,TL