ON THE DETERMINATION OF TURNOVER INVIVO WITH TRACERS

Theoretical and practical aspects of the application of tracer methods for the measurement of turnover of blood-borne compounds are discussed, with special regard to lactate. The validity of the application of the tracer into the aortic arch and sampling from the right atrium (A-V), the administration of tracer into the vena cava and sampling from the aorta (V-A), and sampling to the determination of turnover are examined, using numerical examples. It is shown that the difference between specific activity in arterial and mixed venous blood depends mainly on the cardiac output, the ratio of tracee turnover to the mass of circulating tracee, and the sites of production and utilization of the tracee. Conditions are shown under which the A-V and V-A modes overestimate or underestimate the true rate of turnover. In theory, the A-V mode provides an exact estimate of turnover when the mean specific activity of the tracee in the whole body equals the specific activity of mixed venous blood in the right heart. It is shown that, for compounds with a high turnover rate, the underestimate in the A-V mode is small, and the mode provides a close approximation of true turnover. The underestimate in the V-A mode at high turnover rates is extensive. Experimental evidence indicates that, in several animal species, the specific activity of lactate and several amino acids in several organs and tissues nearly equals that in the venous blood, with the A-V mode providing a close approximation of the true turnover for these compounds. For glucose, sampling the arterial blood (the V-A mode) provides a valid estimate of turnover, but, because of low fractional turnover, the specific activity in arterial and mixed venous blood is nearly identical, with virtually no difference for turnover determined in the two modes.