Circulatory and Metabolic Effects of α-Adrenergic Blockade in the Hyperinsulinemic Ovine Fetus

Objectives: Fetuses of diabetic women exhibit hypoxemia, elevated catecholamine concentrations at birth, and increased incidence of death. Our previous findings suggested that experimental fetal hyperinsulinemia results in a surge in catecholamines with cardiovascular changes supported by increased β-adrenergic activity. The present experiments were designed to assess the contributions of α-adrenergic stimulation to the hemodynamic changes in the hyperinsulinemic ovine fetus.

Methods: Combined ventricular output, regional organ blood flow, vascular resistance, metabolism, and catecholamine concentrations were measured before and during an infusion of insulin and during continued infusion with α-adrenergic blockade (phentolamine) in eight chronically catheterized fetal sheep.

Results: Fetal insulin infusion produced hyperinsulinemic-hypoglycemia, a surge in epinephrine and norepinephrine concentration, and increases in the combined ventricular output (blood flow to the fetus plus placenta) and regional blood flow to the fetus, heart, stomach, gastrointestinal tract, fat, and carcass. In the hyperinsulinemic state, α-adrenergic blockade was associated with additional increases in fetal norepinephrine concentration and no major changes in combined ventricular output or blood flow to the body of the fetus, except for decreased blood flow to the stomach and lungs, and a decrease in stroke volume.

Conclusions: Because vasodilation characterizes the hyperinsulinemic state, α-adrenergic stimulation contributes less to compensatory cardiovascular changes in the hyperinsulinemic fetus then that which we previously have shown for β-adrenergic stimulation.