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).
