Changes in fetal ovine metabolism and oxygen delivery with fetal bypass

Abstract

Since the 1980s, attempts at experimental fetal cardiac bypass for the purpose of correcting severe congenital heart defects in the womb have been hampered by deterioration of placental function. This placental pathophysiology in turn affects transplacental transport of nutrients and gas exchange. To date, the effects of bypass on fetal metabolism and oxygen delivery have not been studied. Nine Suffolk sheep fetuses from 109-121 days gestation were instrumented and placed on fetal bypass for 30 min and followed postbypass for 2 h. Blood gases, glucose, and lactate were serially measured in the fetal arterial and umbilical venous circulations throughout the procedure. Insulin and glucagon levels were serially measured by immunoassay in fetal plasma. Fetal-placental hemodynamics were measured continuously. The expression of glycogen content was examined in fetal liver. Oxygen delivery to the fetus and fetal oxygen consumption were significantly deranged after the conduct of bypass (in-group ANOVA (P = 0.001) and overall contrast (P = 0.072) with planned contrast (P < 0.05) for delivery and consumption, respectively). There were significant alterations in fetal glucose metabolism in the postbypass period; however, insulin and glucagon levels did not change. Fetal liver glycogen content appeared lower after bypass. This is the first report documenting fetal metabolic dysregulation that occurs in response to the conduct of fetal bypass. The significant alterations in fetal oxygen and glucose delivery coupled with hepatic glycogen depletion complicate and impede fetal recovery. These initial findings warrant further investigation of interventions to restore metabolic and hemodynamic homeostasis after fetal bypass.