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.

脑缺血会导致细胞内pH（PHI）减少 大约0.6至1.5或更多单位，细胞内PCO2至 增加到大约200 mmHg。 体外研究表明 细胞内酸中毒增加了脑造成的损伤 缺血。 然而，在体内充分氧合期间 PACO2 = 500 mmHg的高含量酸中毒，这将PHI降低 0.65个单位本身并不有害。 而不是成为原因 低氧/缺血性损伤，PHI的减少可能是表现。 我们的兔子和大鼠实验的一般目的是测试 假设细胞内酸中毒不是IN的决定因素 体内低氧或缺血性脑损伤将通过探索来追求 高碳酸盐，酸中毒， 缺氧和脑损伤：1。如果有足够的氧气供应 可用，是否存在一级细胞内酸中毒 伤害大脑？ 高压室将用于实现 PCO2张力> 1 atm，同时保持足够的PO2张力。 核磁共振（NMR）光谱将在体内使用 为了确定含氧的最低PHI， 高含量大脑。 将使用神经化学来量化伤害 和神经组织学方法以及神经行为结果研究。 2。呼吸酸中毒会增加低氧脑损伤吗？ 将从 同时测量NADH荧光，脑电图监测和 体内NMR光谱。 “关键氧气水平”将是 根据6.9、6.4和6.0的PHI值确定。 3。做麻醉剂 在高碳酸盐期间改变大脑中的“临界氧气” 酸中毒？ 对“关键氧水平”的麻醉作用将 通过在麻醉期间重复第2期研究来检查 与Halothane，Isoflurane和Thiopental。 4。CBF 高碳酸盐（及其相关的酸中毒）的增加 细胞内能状态？ CBF的影响将是 通过比较高碳酸盐诱导的代谢变化和 在两个CBF级别的伤害，一个约有20％的应得 给吲哚美辛给药，每个都具有相同的PACO2。 我们研究的长期目标是：1）定义 PHI降低对代谢和功能性大脑的影响 正直，有和没有麻醉剂的存在； 2） 探索PHI减少之间脑组织中的相互作用 并减少氧气可用性，有或没有一般 麻醉药。 可以监视的新型体内技术 细胞内反应，例如NMR光谱和NADH 荧光将用于定义足够的努力 灌注，组织生存能力和安全边缘 血流不可能进行这种评估的情况 测量和标准生理监测。