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).
