These proposed studies will explore fetal cardiovascular, endocrine, and pulmonary vasculature responses to long-term hypoxia. We will test the overall hypothesis that such hypoxia throughout gestation results in fetal growth retardation. In addition, we will test hypotheses regarding the roles of several hormones in the cardiovascular adaptations to hypoxemic stress. Chronically prepared pregnant sheep (gestational length 147 days) will be exposed to hypoxia either from days - 115 to term by flowing nitrogen gas into their trachea (Group A) or from days 30 to 110 of gestation at high altitude (Barcroft Laboratory, White Mountain, CA, elevation 12,470) (Group B). Then these ewes will be transported to Loma Linda and the hypoxia will be maintained (as the Group A ewes) for-4 weeks. During this month the fetal responses and mechanisms underlying the responses will be examined. Changes in maternal and fetal blood gases, glucose, lactate, vascular pressures, heart rates and blood volumes, uterine blood flow, fetal cardiac output, blood flow distribution to individual organs, and fetal oxygen consumption wt be followed. We will also explore the role of various hormones, including the catecholamines, cortisol, arginine vasopressin and erythropoietin in mediating the vascular responses and/or changes in O2 delivery and use. We also will examine the role of the pituitary (ACTH) and adrenal function (cortisol) during the hypoxic stress. Finally, we will examine the role of long-term hypo)da in pulmonary vascular changes. The results will contribute to an overall understanding of fetal cardiovascular control, and 02 delivery during extended exposure to hypo)da, and the roles of the several hormones in these responses. These studies are of clinical interest concerning the fetuses of women who reside at high altitude, those who smoke, engage in strenuous physical activity, or who are malnourished or anemic, in which conditions the fetus may experience prolonged hypoxic stress and suffer intrauterine growth retardation.
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