The determination of lactate turnover in vivo with 3H- and 14C-labelled lactate. The significance of sites of tracer administration and sampling.

L-[3-3H,U-14C]Lactate was administered to starved rats either as a bolus or by continuous infusion. Tracer administration was performed two ways: injection into the vena cava and sampling from the aorta (V-A mode), or injection into the aorta and sampling from the vena cava (A-VC mode). The specific-radioactivity curves after infusion or injection differed markedly with the two procedures. However, the specific radioactivities of 14C-labelled glucose derived from [U-14C]lactate were similar in the two modes. The apparent turnover rates of lactate calculated from the 3H specific-radioactivity curves in the V-A mode were about half those obtained from the 3H specific-radioactivity curves in the A-VC mode. The apparent contribution of lactate carbon to glucose carbon calculated from specific-radioactivity curves of the A-VC mode was greater than that obtained from the V-A mode. The apparent recycling of lactate carbon calculated from the specific radioactivities for [U-14C]- and [3-3H]-lactate was greater in the A-VC mode than the V-A mode. [U-14C] Glucose was administered in the two modes, but in contrast with lactate the specific radioactivities were only slightly different. An analysis to account for these observations is presented. It is shown that the two modes represent sampling from different pools of lactate. The significance of sites of tracer administration and sampling for the interpretation of tracer kinetics of compounds present in intracellular and extracellular spaces, and with a high turnover rate, is discussed. We propose that for such compounds, including lactate, alanine and glycerol, the widely used V-A mode leads to a marked underestimate of replacement, mass and carbon recycling, and that the A-VC mode is the preferred method for the assessment of these parameters.