Effect of acute umbilical cord compression on hepatic carbohydrate metabolism in the fetal lamb

Abstract

Although the liver plays a central role in glucose homeostasis in the adult, its importance in fetal glucose homeostasis during acute reductions of substrate delivery is unknown. To examine this, we studied eight fetal lambs at 121 ± 2 d gestation. We placed catheters in the descending aorta, inferior vena cava umbilical vein and the left (n = 6) or right (n = 2) hepatic vein, and a balloon occluder around the umbilical cord. At least 4 d after surgery, before and during umbilical cord compression, we measured blood oxygen saturation, glucose, lactate, and Hb concentrations, and blood flows using the radiolabeled microsphere technique. Gluconeogenesis was assessed by infusion of [U14C]lactate. Reducing umbilical flow by 50­60% from a control value of 181 ± 20 mL/min/kg (mean± SD) caused a dramatic decrease in hepatic blood flow from 332 ± 99 to 94 ± 77 mL/min/100 g (p <0.05). Oxygen delivery to the fetus fell by 50% and that to the liver by 73%. However, hepatic 02 consumption was maintained by increased extraction. Glucose delivery to the liver fell from 67 ± 24 to 20 ± 13 mg/min/100 g (p <0.001), but lactate delivery did not change. In spite of the maintenance of lactate delivery, net hepatic lactate uptake fell signifi­cantly from 3.3 ± 1.7 to 1.4 ± 0.9 mg/minlOO g (p <0.05). This could account, in part, for the increase of blood lactate concentration from 16 ± 4 to 27 ± 7 mg/dl. Although hepatic glucose delivery fell markedly, net glucose produc­tion by the liver increased from 0.1 ± 2.4 to 3.9 ± 7.3 mg/ min/100 g (p <0.05). Presumably, this glucose production is from glycogenolysis because no hepatic gluconeogenesis from labeled lactate could be detected. During umbilical cord compression, hepatic glycogenolysis contributed 1.5 ± 2.8 mg/min/kg (30%) of total glucose utilized by the fetus. The mechanisms responsible for fetal hepatic gly­cogenolysis are yet to be delineated. © 1989 International Pediatric Research Foundation, Inc.