Using the near-term chronically catheterized fetal sheep as a model, we will test the hypothesis that regional blood flows are dependent, in part, on the type of electrocortical activity present and on the presence or absence of fetal breathing movements. Experiments will be done during HV-ECOG and LV-ECOG and during fetal breathing movements. Electromagnetic flowmeters plus probes will be used to detect changes in umbilical blood flow during these states and radioactive microspheres will validate these measurements and will be used to measure cerebral blood flow. Sagittal sinus and forelimb artery catheters will permit us to measure A-V cerebral differences for oxygen and glucose. Control studies will be performed to examine the changes in these parameters that occur during HV-ECOG, during LV-ECOG and during fetal breathing movements. We will observe the effects of these changes, the time-dependency of these changes and the effect of the duration of each state on the changes observed. Four experimental protocols will then be executed. 1) Antipyrine will be infused into the fetus. This will throw the fetus into almost continuous HV-ECOG and fetal breathing movements will occur within this type of cerebral activity rather than during LV-ECOG. In this experiment we can observe the effects of fetal breathing movements on regional flows during HV-ECOG and we can also determine whether or not the use of antipyrine creates an artifact in the measurement of regional flows, such that the existing literature will need to be corrected. 2) Hypoxia. Intrauterine hypoxia is one of the more frequent causes of fetal distress. We have designed experiments to see if the various changes in fetal state produce changes in regional flow during hypoxia. We predict that the state requiring the greatest oxygen consumption will be associated with the greatest fetal distress during hypoxia. 3) We will examine the effect of specific cerebral anoxia by restricting the flow to the fetal brain alone. This will enable us to separate out those changes seen during hypoxia which are due solely to cerebral hypoxia and not hypoxia of the myocardium or other tissues. 4) In these studies we will attempt to determine the cause and effect relationships between changes in stimuli seen in the previous experiments. Sound will be used as a stimulus and flow to the temporal cortex will be measured. This will enable us to determine whether flow changes are secondary to central nervous system activity or vice versa.
