BRAIN METABOLISM DURING ANESTHESIA, LOW PH1, AND HYPOXIA

麻醉、低 PH1 和缺氧期间的脑代谢

• 批准号: 3286306
• 负责人: Lawrence Litt
• 金额: $ 18.9万
• 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 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3286306
• 关键词: acid base balance; adenosine triphosphate; anesthetics; blood flow measurement; blood pressure; brain disorder diagnosis; brain electrical activity; brain imaging /visualization /scanning; brain injury; brain metabolism; catecholamines; cerebral ischemia /hypoxia; conduction anesthesia; creatine phosphate; fentanyl; fluorescent dye /probe; halothane; high performance liquid chromatography; hypercapnia; hypoxia; indomethacin; laboratory rabbit; laboratory rat; lactates; neurochemistry; neurophysiology; nuclear magnetic resonance spectroscopy; oxidative phosphorylation; phosphates; respiratory acidosis; respiratory oxygenation; respiratory therapy; thiopental

Cerebral ischemia can cause intracellular pH (pHi) to decrease by approximately 0.6 to 1.5 or more units, and intracellular PCO2 to increase to approximately 200 mmHg. In vitro studies suggest that intracellular acidosis augments the injury produced by cerebral ischemia. During adequate oxygenation in vivo, however, hypercapnic acidosis from PaCO2 = 500 mmHg, which lowers pHi by 0.65 units, is not injurious per se. Rather than be a cause of hypoxic/ischemic injury, decrements in pHi could be manifestation. The general aim of our rabbit and rat experiments, to test the hypothesis that intracellular acidosis is not a determinant of in vivo hypoxic or ischemic brain injury, will be pursued by exploring aspects of the relationship between hypercapnia, acidosis, hypoxia, and cerebral injury: 1. If an adequate supply of oxygen is available, is there a level of intracellular acidosis that injures the brain? A hyperbaric chamber will be used to achieve PCO2 tensions > 1 atm, while maintaining adequate PO2 tensions. Nuclear magnetic resonance (NMR) spectroscopy will be used in vivo to determine the lowest pHi tolerated by the oxygenated, hypercapnic brain. Injury will be quantified using neurochemical and neurohistological methods, and neurobehavioral outcome studies. 2. Is hypoxic brain injury increased by respiratory acidosis? Cerebral oxygen supply and demand will be assessed from simultaneous measurements of NADH fluorescence, EEG monitoring, and in vivo NMR spectroscopy. "Critical oxygen levels" will be determined for pHi values of 6.9, 6.4, and 6.0. 3. Do anesthetics alter "critical oxygen levels" in the brain during hypercapnic acidosis? The anesthetic effect on "critical oxygen levels" will be examined by repeating the studies for issue #2 during anesthesia with halothane, isoflurane, and thiopental. 4. Does the CBF increase during hypercapnia (and its associated acidosis) protect the intracellular energy state? The effects of CBF will be examined by comparing hypercapnia-induced metabolic changes and injury at two CBF levels, one approximately 20% of the other due to indomethacin administration, each having the same PaCO2. The long term objectives of our research are: 1) to define the implications of decreased pHi for metabolic and functional brain integrity, with and without the presence of anesthetics; and, 2) to explore the interaction in brain tissue between decreases in pHi and decreases in oxygen availability, with and without general anesthetics. New in vivo technologies that can monitor intracellular responses, such as NMR spectroscopy and NADH fluorescence, will be applied in efforts to define adequate perfusion, tissue viability, and margins of safety for circumstances where such assessments are impossible with blood flow measurement and standard physiological monitoring.

脑缺血可导致细胞内 pH (pHi) 降低 大约 0.6 至 1.5 或更多单位，细胞内 PCO2 至 增加至约 200 mmHg。 体外研究表明 细胞内酸中毒加重脑损伤 缺血。 然而，在体内充分氧合的情况下， PaCO2 = 500 mmHg 引起的高碳酸血症，会降低 pHi 0.65 单位，本身无害。 而不是成为一个原因 缺氧/缺血性损伤、pHi 下降可能是表现。 我们的兔子和大鼠实验的总体目标是测试 假设细胞内酸中毒不是细胞内酸中毒的决定因素 体内缺氧或缺血性脑损伤，将通过探索来追寻 高碳酸血症、酸中毒、 缺氧和脑损伤： 1.如果氧气供应充足 是否存在一定程度的细胞内酸中毒 伤害大脑？ 高压舱将用于实现 PCO2 张力 > 1 atm，同时保持足够的 PO2 张力。 核磁共振（NMR）光谱将用于体内 确定含氧物质耐受的最低 pHi， 高碳酸血症的大脑。 将使用神经化学物质来量化伤害 和神经组织学方法以及神经行为结果研究。 2.呼吸性酸中毒会加重缺氧性脑损伤吗？ 脑氧供应和需求将通过以下方式进行评估： 同时测量 NADH 荧光、EEG 监测和 体内核磁共振波谱。 “临界氧气浓度”将是 确定 pHi 值为 6.9、6.4 和 6.0。 3. 做麻醉 高碳酸血症期间改变大脑中的“临界氧水平” 酸中毒？ 对“临界氧水平”的麻醉作用将 通过在麻醉期间重复问题 #2 的研究来进行检查 与氟烷、异氟烷和硫喷妥钠一起使用。 4. CBF 是否 高碳酸血症（及其相关的酸中毒）期间增加可保护 细胞内能量状态？ CBF的影响将是 通过比较高碳酸血症引起的代谢变化和 两种 CBF 水平的损伤，其中一种大约是另一种的 20% 至吲哚美辛给药，各自具有相同的 PaCO2。 我们研究的长期目标是： 1) 定义 pHi 降低对大脑代谢和功能的影响 完整性，无论是否存在麻醉剂；以及，2) 探索脑组织中 pHi 降低之间的相互作用 以及氧气供应量的减少，无论是否有一般情况 麻醉剂。 可以监测的新体内技术 细胞内反应，例如 NMR 波谱和 NADH 荧光，将被应用于努力定义足够的 灌注、组织活力和安全边际 无法通过血流进行此类评估的情况 测量和标准生理监测。