Validation of a single-compartment approach to the calculation of secretion rates of ACTH

Abstract

A single-compartment model used in this laboratory for continuously calculating ACTH secretion rates from measured plasma ACTH concentrations was tested for its ability to follow changing rates of ACTH entry (rapid departure from steady state). ACTH was infused at known moderately high but physiological rates into anesthetized dogs (Nembutal). Under such conditions endogenous secretion is initially < 5% of infused rates. Orthogonal polynomials (ACTHt) were fitted to plasma ACTH vs. time data. Then secretion ratet = (ACTHt .times. MCR) + .**GRAPHIC**. where it was previously shown that the metabolic clearance rate of ACTH (MCR) lacked significant interanimal or concentration-dependent variation, and its distribution volume (V) was also constant. The calculated ACTH entry rate curves followed a 10-fold increase in infusion rate over 4 min and subsequent rapid decline with a lag of only about 1 min and, despite some blurring, gave an integrated response equal to 94 .+-. 5.5% of the known signal, and followed a sinusoidal change in infusion rate (amplitude, 1.7 .times. base rate; period, 40 min) with a few percent error and negligible lag. These signals imitate an abrupt stress response and other rapid departures from steady state.