The objective of the proposed studies is to understand the contribution of fetal lymph flow to fluid volume homeostasis in the fetus. Our preliminary studies showed that, in the fetus, thoracic duct lymph flow averages 5 to 10 times adult values on a weight basis. Thus, the fetal lymphatic system appears to be uniquely different from the adult and circulation of fluid through the vascular-interstitial-lymphatic system may play a much greater role in fluid volume regulation in the fetus as compared to the adult. The proposed studies will be performed by catheterizing the left thoracic duct in the chronically catheterized sheep fetus and measuring lymph flow under various conditions. Lymph flow will be measured as a function of time after surgery, and lymph flow rate dependency on outflow pressure will be determined and related to fetal venous pressure. Thoracic duct lymph flow responses to hemorrhage and vascular volume loading will be used to determine the dynamic responsiveness of the fetal lymphatic system. Endocrine and autonomic nervous regulation of lymphatic function will be determined by recording the lymph flow responses to intravascular infusions of specific agonists and antagonists. Specifically, the effects of norepinephrine, epinephrine, angiotensin II, and arginine vasopressin 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 insight 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 #
5R01HD021269-02
Application #
3320085
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1986-01-01
Project End
1988-12-31
Budget Start
1987-01-01
Budget End
1987-12-31
Support Year
2
Fiscal Year
1987
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