Offspring of women with poorly controlled diabetes exhibit hypoxemia, elevated catecholamine concentration at birth, and an increased incidence of fetal death. Experimental fetal hyperinsulinemia results in increased catecholamine concentration and hemodynamic changes including increased combined ventricular output and vasodilation of select fetal organs. We hypothesized that insulin-induced catecholamine-mediated beta-adrenergic stimulation supports some of these hemodynamic changes in the hyperinsulinemic ovine fetus. To study this, 24 chronically instrumented fetal sheep receiving insulin for 24 h were exposed to beta-(propranolol),beta 1-(metoprolol), and beta 2-(ICI 118,551) adrenergic blockade. Insulin infusion resulted in hyperinsulinemic-hypoglycemia, a surge in epinephrine and norepinephrine concentration, and increases in the combined ventricular output and regional blood flow to the heart, adrenal glands, kidney, gastrointestinal tract, liver, fat, muscle, carcass, and placenta. In the hyperinsulinemic state, beta-adrenergic blockade was associated with significant reductions in the combined ventricular output and blood flow to fat, carcass, lungs, and the placenta; beta 1-blockade was associated with reductions in the combined ventricular output and blood flow to the lungs; and beta 2-adrenergic blockade was associated with reductions in blood flow to muscle and lungs. Because beta-adrenergic blockade was associated with reductions in placental blood flow during hyperinsulinemia, oxygen and glucose metabolism were also compromised. We conclude that in the hyperinsulinemic-hypoglycemic normoxemic ovine fetus, insulin-induced catecholamine-mediated hemodynamic changes are modulated in part by beta-adrenergic receptor stimulation.
Fetuses of women whose diabetes is poorly controlled often exhibit hypoxemia and elevated catecholamine concentrations at birth. In the ovine fetus, experimental hyperinsulinemia results in hypoxemia, elevated catecholamine concentrations, and hemodynamic changes. Limited oxygen availability occurring during pregnancy-related complications and/or delivery may present an additional risk to the hyperinsulinemic fetus. In this study, we tested the hypothesis that hypoxia induced via acutely limiting oxygen availability compromises the hemodynamically and metabolically stressed but compensated hyperinsulinemic ovine fetus. Fetuses receiving insulin (n = 8) or placebo (n = 5) for 48 h were exposed to maternally induced hypoxia. Hypoxic hypoxia was associated with a surge in catecholamines in the hyperinsulinemic fetuses. During hypoxia, this group exhibited insulinrelated sustained increases in the combined ventricular output and fetal body blood flow, accentuation of the prior insulinrelated increase in blood flow to the heart, decreased systemic oxygen delivery, accentuation of the insulin-related increased oxygen extraction, reductions in the insulin-related increased systemic oxygen uptake, sustained increases in regional oxygen delivery to the heart and adrenal glands, reductions in the insulinrelated increased delivery to the carcass, and decreased oxygen delivery to the kidneys and gastrointestinal tract. We conclude that, in the hyperinsulinemic ovine fetus, hypoxic hypoxia attenuates the hyperinsulinemia-mediated increased systemic oxygen uptake. Regional oxygen transport is preserved to vital regions (brain, heart, and adrenal glands) by increased perfusion and compromised to certain other regions (kidneys and gastrointestinal tract), because the increases in perfusion are insufficient to offset the limited oxygen availability. (Pediatr Res 38: 67-75, 1995) AbbreviationVo,, oxygen uptake Infants born to women with poorly controlled diabetes mellitus have an increased incidence of in utero hypoxemia (I), perinatal asphyxia (2), hypertrophic cardiomyopathy (3, 4), elevated catecholamine concentrations at birth (5), and perinatal mortality, including unexpected sudden fetal death (3). Hyperinsulinemia has been implicated as a major factor in the pathogenesis of many of these morbidities (3). In the ovine fetus, experimental hyperinsulinemia results in hypoxemia (6-12), elevated catecholamine concentrations (11, 12), and hemodynamic changes (6, 9, 11, 12), simulating several of the abnormalities observed in infants of diabetic mothers.Superimposed hypoxia resulting from abruptio placenta, cord entrapment, and/or difficult or prolonged labor and delivery might present an additional life-threatening risk to the hyperinsulinemic fetus. In the ovine fetus, we (12) and others (6) have previously demonstrated that experimental hyperinsulinemia results in increased combined ventricular output, and blood flow to the heart, adrenal glands, gastrointestinal tract, kidneys, and carcass. In contrast, experimental fetal hyp...
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