The present study is designed to evaluate the mechanism(s) responsible for fetal growth retardation in response to reduced uteroplacental blood flow. During the last four years we have been developing a model of intrauterine growth retardation (IUGR) using a pregnant sheep model in which uteroplacental blood flow has been mechanically reduced. Studies to data have shown a direct relationship (p less than or equal to 0.01) between uteroplacental blood flow and ponderal index, feta body weight, fetal heart and thymus weights and placental weight. The present study is designed to evaluate the mechanisms responsible for fetal growth retardation in response to reductions in uteroplacental blood flow. The first series of studies is designed to complete validation of the sheep model which has shown that graded reductions in uteroplacental blood flow result in graded decreases in fetal growth during the last five weeks of gestation. The second series of studies will evaluate the mechanism by which reduction in uteroplacental blood flow leads to decreased placental size. We will extensively investigate the mechanism by which umbilical blood flow is decreased and placental resistance is significantly increased in IUGR. Furthermore we plan to carefully evaluate changes which occur with internal and external Doppler ultrasound wave profiles (S/D ratios, pulsatile indices) in response to IUGR and vasoconstrictive agents. Changes in systolic and diastolic velocity ratios will be determined and compared using both implanted Doppler flow probes on the uterine and umbilical circulation and external spectral analysis Doppler waveform equipment. Studies are also designed to evaluate if autoregulation of blood blow occurs in the uterine and umbilical circulation. Further investigations are planned in regard to substrate and oxygen delivery and consumption in IUGR and control fetuses. These studies will include evaluation of delivery, extraction and consumption by the uterus, placenta, and fetus. Finally, the effect of increased uteroplacental perfusion (produced by release of the vascular occluder) on substrate delivery, fetal growth, umbilical vascular resistance and umbilical blood flow will be determined in IUGR animals after the vascular occluders have been returned to pre-occlusion values or after administration of oxygen to mother. These studies will result in significant insight into the mechanism of IUGR.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD018370-05
Application #
3315415
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1983-12-01
Project End
1992-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Lang, U; Baker, R Scott; Braems, G et al. (2003) Uterine blood flow--a determinant of fetal growth. Eur J Obstet Gynecol Reprod Biol 110 Suppl 1:S55-61
Lang, Uwe; Baker, R Scott; Khoury, Jane et al. (2002) Fetal umbilical vascular response to chronic reductions in uteroplacental blood flow in late-term sheep. Am J Obstet Gynecol 187:178-86
Lang, U; Baker, R S; Khoury, J et al. (2000) Effects of chronic reduction in uterine blood flow on fetal and placental growth in the sheep. Am J Physiol Regul Integr Comp Physiol 279:R53-9
Carpenter, L B; Baker, R S; Greenberg, S et al. (2000) The role of nitric oxide in mediating adenosine-induced increases in uterine blood flow in the oophorectomized nonpregnant sheep. Am J Obstet Gynecol 183:46-51
Lang, U; Baker, R S; Clark, K E (1997) Estrogen-induced increases in coronary blood flow are antagonized by inhibitors of nitric oxide synthesis. Eur J Obstet Gynecol Reprod Biol 74:229-35
Stek, A M; Baker, R S; Fisher, B K et al. (1995) Fetal responses to maternal and fetal methamphetamine administration in sheep. Am J Obstet Gynecol 173:1592-8
Stek, A M; Fisher, B K; Baker, R S et al. (1993) Maternal and fetal cardiovascular responses to methamphetamine in the pregnant sheep. Am J Obstet Gynecol 169:888-97
Lang, U; Prada, J; Clark, K E (1993) Systemic and uterine vascular response to serotonin in third trimester pregnant ewes. Eur J Obstet Gynecol Reprod Biol 51:131-8
Clark, K E; Irion, G L (1992) Fetal hemodynamic response to maternal intravenous nicotine administration. Am J Obstet Gynecol 167:1624-31
Yang, D; Clark, K E (1992) Effect of endothelin-1 on the uterine vasculature of the pregnant and estrogen-treated nonpregnant sheep. Am J Obstet Gynecol 167:1642-50

Showing the most recent 10 out of 18 publications