Measuring Rates of Appearance in Systems Which are not in Steady State

A general method is advanced for measuring the rate of appearance (production) of a chemical substance in an intact physiological system when this rate is changing with respect to time. The method involves infusing an isotope of this substance at such a rate that specific activity remains constant in space and in time. The means of achieving this constancy are discussed, and the mathematical basis of the method is developed for a fairly general system. An. experiment is described in some detail to show how the rate of endogenous production of glucose in a dog may be calculated when this rate is changing quite rapidly.