Thresholds for physiological effects of plasma catecholamines in fetal sheep

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.