These studies are designed to address the overall hypothesis that eicosanoids are intrinsic modulators of the neonatal cerebral circulation.
Specific aims i nvolve 1) determination of the relationship between cerebral prostanoids (PGs) and cerebral blood flow during control conditions and during interventions which alter cerebral hemodynamics, 2) definition of the functional significance of the relationship between PGs and cerebral hemodynamics, 3) investigation of the interactions between PGs and other vasoactive mediator systems, and 4) exploration of the possibility that leukotrienes could be involved in cerebral blood flow regulation in neonates. Methods to be employed include several approaches which previously have not been applied to examining cerebral vascular responses in newborns including: 1) direct observation and measurement of pial arterial diameters using a cranial window method, 2) continuous measurement of blood flow through pial arteries by coupling measurements of vessel diameters with continuous determination of blood flow velocity using pulsed-Doppler crystals, 3) measurements of pressure within pial vessels using a micropipette servo-null transducer system which allows calculation of vascular resistances of various size vessels when coupled with blood flow measurements, and 4) sampling of CSF as it passes over the cerebral surface using a cranial window. In addition, traditional methods will be employed including radioactively-labeled microsphere determinations of cardiac output and distribution (total and regional cerebral blood flow), radioimmunoassays and radioenzymatic assays of vasoactive mediators, and continuous monitoring of carotid blood flow using pulsed-Doppler flow probes. This investigation of the role of eicosanoids in regulation of cerebral blood flow in the neonatal animal will contribute important new information which ultimately may be of considerable value in managing sick neonates since disorders of cerebral circulation are frequent causes of neonatal morbidity and mortality.
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