Sample site selection for tracer studies applying a unidirectional circulatory approach

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Abstract
The optimal arterial or venous sites for infusion and sampling during isotopic tracer studies have not been established. This study determined the relationship of plasma and tissue enrichment (E) when isotopes were infused in an artery and sampled from a vein (av mode) or infused in a vein and sampled from an artery (va mode). Adult dogs were given primed constant infusions of [3-13C]lactate, [1-13C]leucine, and 14C-labeled bicarbonate. Simultaneous samples were drawn from the vena cava, aortic arch, and breath. Tissue samples were removed from skeletal muscle, liver, kidney, and gut. Breath samples were analyzed for 14CO2 by liquid scintillation counting and plasma isotopic enrichments of [13C]lactate, [13C]leucine, and alpha-[13C]ketoisocaproate (KIC) were determined by gas chromatography-mass spectrometry. By using the va mode, the plasma E for lactate and leucine were 30-40% above tissue E. The av mode provided an accurate reflection of tissue E for lactate, which equilibrates rapidly with tissues, and a reasonable estimate for leucine, which exchanges more slowly. The isotopic enrichment of plasma KIC more directly reflected tissue leucine E than did plasma leucine E, and KIC enrichment was insensitive to sampling site. We also evaluated theoretically a circulatory model that predicts venous isotopic enrichments when the va mode is used. We conclude that the av mode is optimal but that the problems arising from use of the va mode can be overcome by use of a metabolic product (i.e., KIC) or by calculation of venous specific activity with our circulatory mode.