CEREBRAL OXIDATIVE METABOLISM IN HYPOXIC NEWBORNS

拟议的研究调查了脑代谢反应， 通过不同强度的缺血和缺氧诱导新生动物， 持续时间 脑代谢将通过体内测量 细胞内磷代谢产物和细胞内pH的核磁共振研究 ~（31）P共振和脑组织同步测量 氧、葡萄糖和乳酸的代谢率。 31-P核磁共振谱 允许重复和定量测量的动态方面， 有机磷代谢和细胞内的pH值在完整的动物。 由于全身或局部变化而发生的血流动力学事件 氧含量将与代谢改变有关， 新生动物出现短暂或永久性组织损伤。 实验方案将在新生仔猪和羔羊上进行， 研究大脑能量储备的极限， 31-急性缺氧和缺血中的体内磷NMR光谱， 确定向大脑输送氧气的临界水平（取决于 占主导地位的代谢需求）。 氧气和二氧化碳的生理测量 葡萄糖利用率和摄取、酸碱平衡和血流动力学 测量结果将与含磷代谢相关 化合物. 这些项目将测试整体假设，单一或 反复发作的缺氧和代谢应激，以及长期的 缺氧状态，可能导致代谢功能的微妙改变。 具体研究将调查补偿机制的效率 在一定条件下维持新生动物的细胞脑代谢 受损的氧合，并将建立这种效率的限制， 比较不同时期的微循环和代谢反应， 通过NMR和CBF测量鉴定损伤。

The proposed studies investigate the cerebral metabolic responses of newborn animals induced by ischemia and hypoxia of varying intensity and duration. Cerebral metabolism will be assessed by in-vivo measurements of phosphorus cellular metabolites and intracellular pH with nuclear magnetic resonance of 31-Phosphorus and simultaneous measurements of cerebral metabolic rate for oxygen, glucose, and lactate. 31-P NMR spectroscopy allows repetitive and quantitative measurements of the dynamic aspects of metabolism of organophosphates and intracellular pH in the intact animal. Hemodynamic events occurring as a result of general or regional changes in oxygen content will be related to metabolic alterations reflecting the onset of transient or permanent tissue damage in newborn animals. Experimental protocols will be carried out on newborn piglets and lambs, investigating limits in brain energy reserves as identified by 31-Phosphorus NMR spectroscopy in-vivo in acute hypoxia and ischemia, identifying the critical level of oxygen delivery to brain (depending on the prevailing metabolic demand). Physiologic measurements of oxygen and glucose availability and uptake, acid-base balance, and hemodynamic measurements will be correlated with metabolic phosphorus containing compounds. These projects will test the overall hypotheses that single or repeated episodes of hypoxic and metabolic stress, as well as long-lasting states of hypoxia, may result in subtle alterations of metabolic function. Specific studies will investigate the efficiency of compensatory mechanisms maintaining cellular brain metabolism in newborn animals under conditions of impaired oxygenation and will establish the limits of this efficiency by comparing the microcirculatory and metabolic responses during various insults identified by NMR and CBF measurements.