These studies will explore the fetal responses to long-term hypoxemia. Chronically prepared pregnant sheep will be exposed to hypoxia in an environmental chamber for periods of up to 3 weeks and the fetal responses and mechanisms underlying those responses examined. Changes in 02 delivery to individual organs, total fetal 02 consumption cardiac output, blood flow distribution, blood volume, vascular pressures, and heart rate will be followed through not only the short-term but also the long-term phase of hypoxia. We will also explore the role of various hormones, including the catecholamines, AVP, renin, and erythropoietin, in mediating the vascular responses and/or changes in 02 delivery and use. We will examine the role of fetal cardiac function and venous return in regulating cardiac output during the hypoxic stress. Specifically we will determine the effects of the sympathetic nervous system, circulating catecholamines, and afterload (arterial pressure) on cardiac function at different stages during hypoxia. We will also examine the changes in mean systemic filling pressure, resistance to venous return, and vascular compliance and their effect on venous return during the hypoxia. When completed the results will be integrated, using a systems analysis approach, into an overall understanding of cardiovascular control, 02 delivery, and 02 use during extended exposure to hypoxia. These studies are of interest concerning the fetuses of women who reside at high altitude, smoke, engage in strenuous physical activity, or who are malnourished, anemic, or exposed to environmental pollution in which conditions the fetus may experience prolonged hypoxic stress.
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