In the newborn it is extremely important to keep the brain well oxygenated in order to avoid irreversible loss of function. We have developed new imaging technology to obtain high resolution (< 5 um/pixel), quantitative, two dimensional maps oxygen pressure in the veins and capillary beds of the cortex, as well as of intracellular pH and intracellular Ca2+ concentrations in the surface layers of cell of the brain cortex. These metabolite maps, measured in newborn piglets, will allow us to quantitate the dependence of oxygenation and cellular physiology of the cortex on PaCO2, PaO2, blood pH and systemic blood pressure. the """"""""critical"""""""" oxygen pressures in the capillary beds of the cortex i.e. those below which alterations are observed in EEG, intracellular pH or intracellular Ca2+ concentration, will be determined. The severity and duration of each hypoxia/metabolic perturbation require to cause irreversible damage, as indicated by failure of the measured parameters to recover normal values, will also be determined. Specifically we will: A. Quantitate the dependence of cortical oxygen pressure and function on PaCO2. B. Quantitate the dependence of delivery of oxygen to the cortex effect on systemic blood pressure. C. Quantitate the interactions of PaCO2 and PaO2 in regulating the local microvascular system of the cortex. D. Determine the effect of metabolic acidemia on cortical oxygenation and function. E. Evaluate the role of microvascular damage in irreversible damage to brain function. Collaborative studies will be carried out to correlate the above parameters with neurotransmitter metabolism as evaluated by microdialysis. These measures will permit critical evaluation of the efficacy of treatments designed to optimize oxygen delivery and to reduce irreversible damage to the brain of the newborn.
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