The long term objective of the proposed research is to characterize and provide quantitative indices of the sensitivity of the neonatal brainstem evoked potential (BAEP) to alterations in arterial blood chemistry (ABC) and cerebral blood flow (CBF). The overall hypothesis of the proposed research is: Neonatal brainstem function sensitivity to alterations in ABC and CBF is age-dependent. This hypothesis will be tested as follows: The BAEP will be elicited, analyzed, and used as an index of brainstem function in very premature and full-term neonatal lambs. These animals will be studied at three experimentally controlled and independently varied levels of arterial carbon dioxide tension (PaCO(2)), pH, and CBF. Under each condition: 1) arterial oxygen tension (PaO(2)) will be held constant; 2) ABC and central hemodynamic status will be measured and/or calculated; 3) regional CBF, vascular resistance, and cerebral perfusion pressure will be measured and/or calculated. Utilizing this approach, the specific aims of the proposed research are to quantitatively determine the sensitivity of the neonatal BAEP to PaCO(2), pH, and CBF. These data will be further analyzed to identify a potential perfusion and age-dependent mechanism associated with PaCO(2), pH, or CBF induced alterations in the BAEP. This multidisciplinary study represents the first attempt to identify the sensitivity of neonatal brainstem function, and the BAEP in particular, to discrete and independent alterations in arterial blood chemistry and perfusion. Furthermore, it is particularly noteworthy that this study will incorporate techniques which will enable these factors to be studied over an age range previously limited to fetal animal preparations. As such the results should provide unique information regarding brainstem function at particularly vulnerable stages of development. Such information should be relevant to the clinical management of the increasing number of prematurely delivered infants and expand our understanding of maturational changes in CNS responsiveness at a basic science level.
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