The risk of perinatal death, chronic lung problems, or neurological impairment is highest in the extremely premature infant because of their poor ability to adapt to extrauterine life. Specifically, viability and development are significantly jeopardized by predisposing factors associated with immmaturity which compromise oxygenation. The understanding of basic biological function at this early stage of development has been impeded by the lack of an appropriate in vivo experimental animal model. Recent advancements in liquid ventilation techniques have demonstrated that the immature lamb, as young as 106 days of gestation, can be studied independent of the umbilical-placental circulaton in an extrauterine environment. This experimental approach provides the first opportunity to study physiological responses in an animal model resembling the perinatal status of the extremely premature infant. The proposed research will utilize this model to investigate whether systemic cardiopulmonary, hemodynamic, and metabolic responses to alterations in arterial oxygenation adequately regulate oxygen supply and oxygen demands to support functional activity. Furthermore, because of the importance of cerebral function on viability, growth and development, the proposed experiments will also examine local cerebral hemodynamic and metabolic responses, as well as the relationship between cerebral oxygen supply, oxygen demand and functional activity. This research should provide further understanding of basic biological development which can facilitate the continual advancement of neonatal clinical management.
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