BRAIN METABOLISM DURING ANESTHESIA, LOW PH1, AND HYPOXIA

脑缺血可导致细胞内pH（pHi）降低， 约0.6至1.5或更多单位，以及细胞内PCO 2至 升高至约200 mmHg。 体外研究表明， 细胞内酸中毒加重脑损伤 缺血 然而，在体内充分充氧期间， PaCO 2 = 500 mmHg的高碳酸血症性酸中毒，使pHi降低， 0.65单位，本身并不有害。 而不是导致 缺氧/缺血损伤，可表现为pHi降低。 我们的兔子和大鼠实验的总体目标是， 假设细胞内酸中毒不是一个决定因素， 体内缺氧或缺血性脑损伤，将通过探索追求 高碳酸血症，酸中毒， 缺氧和脑损伤：1.如果有足够的氧气 是否存在一定程度的细胞内酸中毒， 会伤到大脑吗 一个高压舱将被用来实现 PCO 2张力> 1 atm，同时保持足够的PO 2张力。 将在体内使用核磁共振（NMR）光谱法 为了确定氧化物耐受的最低pHi， 高碳酸血症的大脑。 损伤将使用神经化学 神经组织学方法和神经行为结果研究。 2.呼吸性酸中毒会加重缺氧性脑损伤吗？ 脑氧供应和需求将从 同时测量NADH荧光、EEG监测和 体内NMR光谱法。 “临界氧气水平”将是 测定pHi值为6.9、6.4和6.0。 3.做麻醉药 在高碳酸血症期间改变大脑中的“临界氧水平” 酸中毒？ 麻醉剂对“临界氧含量”的影响将 通过在麻醉期间重复问题2的研究进行检查 氟烷异氟烷和硫喷妥钠 4. CBF是否 高碳酸血症（及其相关的酸中毒）期间增加保护 细胞内的能量状态 CBF的效果将是 通过比较高碳酸血症引起的代谢变化和 两个CBF水平的损伤，一个约为另一个的20%， 吲哚美辛给药，每种药物具有相同的PaCO 2。 我们研究的长期目标是：1）确定 pHi降低对大脑代谢和功能的影响 完整性，存在和不存在麻醉剂;以及，2） 探索脑组织中pHi降低与 和氧气供应量的减少，有和没有一般 麻醉剂 新的体内技术可以监测 细胞内反应，如NMR光谱和NADH 荧光，将被应用于努力定义足够的 灌注、组织活力和安全范围， 在血流情况下无法进行此类评估的情况下 测量和标准生理监测。

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.