BRAIN METABOLISM DURING ANESTHESIA, LOW PH1, AND HYPOXIA

脑缺血可引起细胞内pH(Phi)降低 大约0.6到1.5个或更多个单位，细胞内二氧化碳达到 增加到大约200毫米汞柱。体外研究表明， 细胞内酸中毒加重脑组织损伤 缺血症。然而，在体内充分充氧的过程中， 二氧化碳分压=500毫米汞柱引起的高碳酸盐酸中毒，使PHI降低 0.65单位，本身并不有害。而不是成为 缺氧性/缺血性损伤，可表现为PHI降低。 我们的兔子和大鼠实验的总体目的是测试 细胞内酸中毒不是In的决定因素的假说 体内缺氧或缺血性脑损伤，将通过探索来进行 高碳酸血症、酸中毒、 缺氧与脑损伤：1.如果有足够的氧气供应 是否存在某种程度的细胞酸中毒 会伤及大脑？高压舱将被用来实现 二氧化碳压力和1个ATM，同时保持适当的二氧化碳压力。 核磁共振波谱将在活体中使用 为了确定含氧者所能容忍的最低PHI， 高碳酸血症的大脑。损伤将使用神经化学物质进行量化 以及神经组织学方法和神经行为结果研究。 2.呼吸性酸中毒是否加重了缺氧性脑损伤？ 将从以下方面评估脑氧供应和需求 同时测量NADH荧光、脑电监测和 活体核磁共振波谱。“临界含氧量”将是 已针对PHI值6.9、6.4和6.0确定。3.服用麻醉药 高碳酸血症时脑内“临界氧水平”的改变 酸中毒？麻醉对“临界血氧水平”的影响 在麻醉过程中通过重复问题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(及其相关酸中毒)期间的增加保护 细胞内的能量状态？CBF的影响将是 通过比较高碳酸血症引起的代谢变化和 两个CBF级别的伤害，其中一个约占另一个的20% 给吲哚美辛给药，每个都有相同的PaCO2。 我们研究的长期目标是：1)界定 PHI降低对新陈代谢和脑功能的影响 完整性，在麻醉剂存在和不存在的情况下；2) 探讨PHI降低在脑组织中的相互作用 以及氧气利用率的下降，在有和没有一般情况下 麻醉剂。新的活体技术可以监测 细胞内反应，如核磁共振波谱和NADH 荧光，将应用于努力定义足够的 灌注量、组织活力和安全边际 在有血液流动的情况下不可能进行这种评估 测量和标准的生理监测。

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.