Cerebral palsy and mental retardation are associated with a history of abnormally low cerebral blook flow (CBF) in infants. Asphyxia is the common clinical condition associated with abnormal CBF. Mechanisms which normally operate to ensure adequate blood flow to the brain (autoregulation) may be compromised by neonatal asphxia. A controlled systematic study of the affect of asphyxia on CBF autoregulation in the newborn lamb, a well documented model for the sutdy of neonatal CBF physiology. More specifically, we will measure CBF while changing arterial pressure. We will define the range of arterial pressures within which the lamb brain can maintain constant flow. These limits will be clearly defined. Once the limits of autoregulation are established, the effect of hypoxia, hypercapnia, or acidosis on CBF and the pressure-flow relationships will be analyzed. Cerebral blood flow will be measured with the radiomicrosphere technique. With this technique, we can measure regional changes in cerebral blood flow to examine the hypothesis that the brain redistributes its blook flow when stressed to protect structures most important for survival. Arterial and cerebral venous concentration of oxygen and glucose will be measured (via a catheter placed in the superior sagittal sinus) to evaluate oxygen delivery and consumption and glucose utilization of the brain. With these parameters we will be able to analyze the metabolic consequences of the experimiental challenges. These studies may promote a more rational physiologic basis for clinical intervention in the management of asphyxiated infants.
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