Thresholds for physiological effects of plasma catecholamines in fetal sheep

Abstract

To clarify the physiological role for the marked increases in circulating norepinephrine (NE) and epinephrine (E) that occur at birth, we performed graded infusions of NE and E in preterm (131 days) and full-term (142 days) fetal sheep. A variety of hemodynamic, metabolic, and endocrine responses to stepwise increases in plasma catecholamine levels were analyzed by computer-based graphical analysis of the dose-response curves. We determined the "threshold" value or minimum plasma concentration necessary to produce discernible effects. We observed increases in systolic blood pressure, diastolic blood pressure, and dP/dt beginning at plasma concentrations of 500-800 pg/ml of NE or E. In contrast, increases in plasma free fatty acid and glucose levels were observed at E concentrations as low as 50-100 pg/ml. Full-term animals had generally lower thresholds and higher peak responses than preterm animals. Because these thresholds for infused NE and E are well within the range of plasma catecholamine values seen at birth, these results underscore the importance of circulating catecholamines in the events of neonatal adaptation.

Desensitization of β-Receptor Mediated Responses to Epinephrine in Fetal Lambs by Prolonged Ritodrine Administration

“…Comparison with the more recent observations of Padbury et a/. (16) suggests that the lower dose (-0.28 g/kg.min-') would establish plasma epinephrine concentrations of -1000 pg/ mL, whereas the higher dose during the 2nd hour of infusion would establish concentrations in the range of 2500-3000 pg/ mL; both concentration ranges are well above the thresholds established by Padbury et al (16) for responses in all the parameters measured during our present study. The changes observed during the initial control studies, before ritodrine infusion, confirm this.…”

“…In our study, we have investigated effects of prolonged ritodrine administration to fetal lambs on a number of well-characterized metabolic, endocrine, and cardiovascular responses to a standard test infusion of epinephrine (13)(14)(15)(16) to assess further how the drug may influence responsiveness to physiologic elevation of adrenal catecholamine release.…”

Characterization of glucose-insulin responsiveness and impact of fetal number and sex difference on insulin response in the sheep fetus

“…At the higher glucose concentrations in the step-up clamps, we expect that hypoxemia and subsequent elevation of plasma norepinephrine concentrations would be further exacerbated (44). These concentrations of norepinephrine may exceed the threshold necessary to inhibit insulin secretion (19,20,25,35), thus providing a physiological explanation for lower insulin secretion when plasma glucose concentrations are raised above 3.4 mmol/l.…”

Effect of Birth-Related Events on Metabolism in Fetal Sheep

“…Oxygenation and umbilical cord occlusion during intrauterine cooling increase plasma FFA and glycerol concentrations (5,6). Plasma epinephrine concentrations increased in the present study above the threshold required for lipolysis (29). The fetal heart and skeletal muscle have the capacity to metabolize fatty acids and ketones (42).…”

“…Although fetal catecholamine concentrations increased with ventilation and oxygenation, these changes alone were insuficient to increase fetal oxy- oxygen consumption alone and in combination with oxygenation and umbilical cord occlusion (5,6). Other important factors are study, plasma epinephrine concentrations increased during venincreases in muscle activity and organ function and normal tilation to values shown to increase fetal blood glucose concenprenatal thyroid function, which is essential for the postnatal rise trations (29). Epinephrine probably stimulated glycogenolysis in oxygen consumption (3).…”