IN-VIVO CEREBRAL OXIDATIVE METABOLISM IN HYPOXIC NEWBORN

拟议的研究调查了脑部代谢反应 不同强度和程度的缺血缺氧所致新生动物 持续时间。大脑新陈代谢将通过体内测量 含磷细胞代谢物和胞内pH与核磁 ~(31)P的共振和脑组织的同步测量 氧、葡萄糖和乳酸的代谢率。~(31)P核磁共振波谱 允许对动态方面的重复和定量测量 有机磷在完整动物体内的代谢和细胞内pH。 整体或区域性变化导致的血液动力学事件 氧含量将与代谢变化有关，反映 新生动物出现一过性或永久性组织损伤。 实验方案将在新生的小猪和羔羊身上进行， 调查大脑能量储备的限度，由 急性缺氧缺血时体内的31-磷核磁共振波谱， 确定向大脑输送氧气的临界水平(取决于 主要的代谢需求)。氧和氧的生理学测量 葡萄糖的利用和摄取、酸碱平衡和血流动力学 测量结果将与代谢性磷含量相关联 化合物。这些项目将检验总体假设，即单一或 反复发作的低氧和代谢应激，以及长期的 处于缺氧状态，可能会导致代谢功能的微妙变化。 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脑细胞代谢 并将通过以下方式确定这种效率的限度 比较不同时间段的微循环和代谢反应 由核磁共振和CBF测量确定的侮辱。

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.