MECHANISMS OF PERINATAL CEREBRAL BLOOD FLOW REGULATION

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The goal of these studies is to continue work in the neonatal lamb post asphyxia model to pursue an understanding of mechanisms of perinatal brain injury. One set of studies is designed to examine the response of the cerebral circulation to hypocarbia in the "stressed" newborn lamb. Utilizing radiolabelled microsphere methodology and a sagittal sinus catheter to sample cerebral venous drainage, cerebral blood flow, 02 delivery, 02 consumption, and fractional 02 extraction will be measured or calculated. The first of these studies will examine the response of the cerebral circulation to hypocarbia in the post asphyxia newborn lamb while the second set will examine the same issue in a newly developed newborn lamb pulmonary hypertension model. Hyperventilation is used clinically most frequently in asphyxiated infants with pulmonary hypertension. These studies will go a long way towards assessing the safety of hyperventilation therapy in sick newborn infants. The other 3 studies will consider mechanisms of brain injury after asphyxia. The central hypothesis is that much of the brain injury associated with asphyxia occurs after rather than during the event. These studies will utilize the newborn lamb post asphyxia model. One set of studies will evaluate developmental differences in post asphyxia mitochondria function. A second study will assess neurophysiologic and pathologic consequences of asphyxia while the third group of studies will assess the effect of preasphyxia glucose concentration on neurophysiologic and pathologic sequelae of asphyxia and on post asphyxia mitochondria function. An underlying theme in many of these studies will be the role of oxygen free radicals in post the asphyxia neurophysiologic, mitochondrial, and pathologic sequelae. The importance of these studies is the ultimate goal of minimizing post asphyxia CNS injury with specific therapeutic interventions.