Effects of prolonged fetal hyperinsulinemia on plasma catecholamines, circulation and oxygen metabolism in utero

The effects of pharmacologic hyperinsulinemia on changes in plasma catecholamines, circulation and oxygen metabolism were examined in fetal sheep. Sequential incremental doses of 0.2 and 0.4 U.kg-1.h-1 of porcine insulin were infused into fetal sheep for 24 h each, for a total of 48 h; pharmacologic fetal insulin concentrations were achieved. Fetal hyperinsulinemia resulted in fetal hypoxemia on the basis of reduced umbilical venous oxygen content. Fetal oxygen extraction increased and oxygen uptake did not change. Prolonged fetal hyperinsulinemia with hypoxemia was also associated with hypoglycemia and a surge in fetal plasma catecholamine concentration. Heart rate and fetal body blood flow also increased. This increased blood flow to the fetal body resulted from increased blood flow to vital organs, including heart and adrenal glands, and insulin-sensitive tissues, including gastrointestinal tract and carcass, without reductions in blood flow to other fetal organs. These changes in regional vascular perfusion maintained oxygen delivery to individual fetal organs similar to values before insulin infusion. We conclude that the ovine fetus has a remarkable ability to compensate for pharmacologic hyperinsulinemia of 48 h duration, which resulted in hypoxemia, hypoglycemia, and a surge in plasma catecholamine concentration, and that appropriate fetal adaptations maintained fetal oxygen consumption and regional oxygen delivery to individual fetal organs.