The overall purpose of these experiments is to explore the mechanisms by which the fetal cardiovascular system adapts to long-term hypoxemia. Specifically, we plan to explore changes in fetal cardiac function during hypoxemia. We have previously shown fetal right ventricular output and function to decrease on day 3 of hypoxemia, but then to return to normal by 2 weeks and possibly to even rise above normal with continued hypoxemia. Because timing and duration of hypoxic exposure are probably crucial, we will examine sheep exposed to hypoxemia for 2-3 weeks in the last third of gestation as well as those exposed from day 30 of gestation onward. Change in cardiac performance could result from alterations in delivery, transfer, and utilization of O2 by the myocardial cell, alterations in myocardial cel energy production, and/or changes in the contactile mechanism of the cells. Therefore, we plan to examine 1) changes in coronary blood vessel reactivit that might affect O2 delivery, 2) changes in number and geometry of myocardial capillaries and mitochondria that might affect O2 transfer, 3) changes in myocardial cell oxygen consumption and metabolic enzyme levels that might affect O2 utilization and energy production, and 4) changes in contractile machinery and ability utilizing isolated papillary muscle. Thus, results will contribute to an overall understanding of fetal cardiovascular control and O2 delivery during extended periods of hypoxemia These studies are of clinical importance relative to fetus of women who reside at high altitude, those who engage in strenuous physical activity, those who are malnourished, and those who smoke.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD022190-06
Application #
3321598
Study Section
Reproductive Biology Study Section (REB)
Project Start
1986-08-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
6
Fiscal Year
1992
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
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
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
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

Showing the most recent 10 out of 16 publications