The long-term objectives of the proposed studies are two fold: 1) understand the dynamics and control of lymph flow in the fetus and 2) to understand the contribution of lymph flow to fluid volume homeostasis in the fetus. Data generated thus far show that the lymphatic system in the fetus is uniquely different from that in the adult in that lymph flow rates and lymph protein fluxes are several times higher in the fetus relative to body weight. Thus the lymphatic system will play a much greater role in fluid volume regulation in the fetus as compared to the adult. The proposed studies will be performed by chronically catheterizing the left thoracic lymph duct and measuring lymph flow under various conditions. More specifically, the studies are desinged to determine to what extent fetal lymph flows vary with gestational age and to determine whether the autonomic nervous system contributes to either the high basal flow rate and/or its extensive short-term variability. Potential endocrine modulation of the fetal lymphatic system will be explored by determining whether specific agonists or antagonists to arginine vasopressin, norepinephrine or angiotensin II receptors alter lymphatic pumping ability and thereby alter the lymph flow function cutve (the relationship between lymph flow and outflow pressure). In addition, the effects of increasing fetal hydration on lymphatic pumping ability will be explored. Overall, these studies will not only provide important information about the dynamics and control of whole-body lymph flow in the normal fetus but they will also provide insights into the understanding of fetal blood volume regulation, fetal fluid balance, and clinical problems such as non- immune hydrops fetalis (ie, fetal edema).

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD021269-04
Application #
3320083
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1986-01-01
Project End
1993-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Davis, L E; Hohimer, A R; Brace, R A (1996) Changes in left thoracic duct lymph flow during progressive anemia in the ovine fetus. Am J Obstet Gynecol 174:1469-76
Brace, R A (1995) Thoracic duct lymph flow responses to hemorrhage in the ovine fetus. Am J Physiol 269:H1277-81
Brace, R A (1994) Blood volume response to drainage of left thoracic duct lymph in the ovine fetus. Am J Physiol 266:R709-13
Brace, R A (1993) Maximal lymph flow in the ovine fetus. Am J Obstet Gynecol 169:1487-92
Brace, R A; Valenzuela, G J (1990) Effects of outflow pressure and vascular volume loading on thoracic duct lymph flow in adult sheep. Am J Physiol 258:R240-4
Brace, R A (1989) Thoracic duct lymph flow and its measurement in chronically catheterized sheep fetus. Am J Physiol 256:H16-20
Brace, R A (1989) Effects of outflow pressure on fetal lymph flow. Am J Obstet Gynecol 160:494-7
Gold, P S; Brace, R A (1988) Fetal whole-body permeability--surface area product and reflection coefficient for plasma proteins. Microvasc Res 36:262-74
Brace, R A (1988) Fetal thoracic duct lymph flow response to intravascular saline infusion. Am J Physiol 254:R1007-10