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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD022190-01
Application #
3321592
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Loma Linda University
Department
Type
Schools of Medicine
DUNS #
City
Loma Linda
State
CA
Country
United States
Zip Code
92350
Gilbert, R D (1998) Fetal myocardial responses to long-term hypoxemia. Comp Biochem Physiol A Mol Integr Physiol 119:669-74
Browne, V A; Stiffel, V M; Pearce, W J et al. (1997) Cardiac beta-adrenergic receptor function in fetal sheep exposed to long-term high-altitude hypoxemia. Am J Physiol 273:R2022-31
Ohtsuka, T; Browne, V A; Gilbert, R D (1997) Oxygen dose-response curve of cardiac papillary muscle from fetal and nonpregnant adult sheep exposed to long-term, high-altitude hypoxemia. J Soc Gynecol Investig 4:197-202
Browne, V A; Stiffel, V M; Pearce, W J et al. (1997) Activator calcium and myocardial contractility in fetal sheep exposed to long-term high-altitude hypoxia. Am J Physiol 272:H1196-204
Hu, X Q; Longo, L D; Gilbert, R D et al. (1996) Effects of long-term high-altitude hypoxemia on alpha 1-adrenergic receptors in the ovine uterine artery. Am J Physiol 270:H1001-7
Kamitomo, M; Ohtsuka, T; Gilbert, R D (1995) Effects of isoproterenol on the cardiovascular system of fetal sheep exposed to long-term high-altitude hypoxemia. J Appl Physiol 78:1793-9
Ohtsuka, T; Gilbert, R D (1995) Cardiac enzyme activities in fetal and adult pregnant and nonpregnant sheep exposed to high-altitude hypoxemia. J Appl Physiol 79:1286-9
Kamitomo, M; Longo, L D; Gilbert, R D (1994) Cardiac function in fetal sheep during two weeks of hypoxemia. Am J Physiol 266:R1778-85
Kamitomo, M; Alonso, J G; Okai, T et al. (1993) Effects of long-term, high-altitude hypoxemia on ovine fetal cardiac output and blood flow distribution. Am J Obstet Gynecol 169:701-7
Kamitomo, M; Longo, L D; Gilbert, R D (1992) Right and left ventricular function in fetal sheep exposed to long-term high-altitude hypoxemia. Am J Physiol 262:H399-405

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