ANESTHETIC PROTECTION IN BRAIN HYPOXIA: A P31 NMR STUDY

我们提出了一项关于大鼠缺氧缺血性脑损伤的体内研究。 麻醉大鼠的~(31)P和~1H核磁共振波谱。我们的目标是评估 预测和促进脑损伤的因素，并比较 硫喷妥钠、异氟醚、氟烷和 芬太尼。氯胺酮，一种不保护大脑的麻醉剂，将被 研究并与其他药剂进行了比较。以下是四个基本问题 解决：1)不同的麻醉剂如何改善低氧 和缺血性脑损伤？2)体内核磁共振波谱多快可以 确定发生了不可逆转的损伤？3)过程中是否存在缺氧 麻醉比全脑缺血造成的损伤更多？4)当低氧和 麻醉过程中发生缺血性脑损伤，麻醉过程中损伤程度有多大？ 再灌流？ 我们的研究将使用一台水平核磁共振光谱仪，它的磁场 强度为5.6特斯拉。麻醉的大鼠将俯卧在一个区域 高磁场均匀度，并将使用14毫米低 噪声表面线圈探测器。~(31)P核磁共振波谱将在 在高氧、低氧和全脑缺血期间的活体(使用 Pulsinelli模型)，并用于确定细胞内pH和 细胞内的三磷酸腺苷、聚合酶链式反应、磷脂酰肌醇和单磷酸糖的浓度。1H 光谱学将在类似的条件下单独进行研究 细胞内乳酸和N-乙酰天冬氨酸的浓度。 将使用磁化传递法来测量单向 肌酸激酶(CPK)和肌酸激酶的通量和单向速率常数 三磷酸腺苷合成酶反应。能源储备的恶化和恢复将 在缺氧和缺血过程中进行研究，并与侵袭性相关 膜磷脂和游离脂肪酸的死后测量， 由合作者使用冷冻提取技术和高效液相色谱完成。 体外研究表明，新陈代谢和电活动可以恢复 缺氧和缺糖20至20天的中枢神经系统神经元恢复正常 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往往会导致永久性损伤。我们 希望我们对不同麻醉剂的体内研究将表明 人类的治疗策略，延长了大脑对 减少缺氧，减少术中脑损伤的可能性。

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.