First-pass effect of an intravenous bolus of [C-13] bicarbonate displayed breath-by-breath

The dilution of an intravenous bolus dose of [C-13]bicarbonate is used as a n estimate for the metabolic rate under certain conditions. It is a consist ent finding in all studies that the total amount of intravenous [C-13]bicar bonate cannot be recovered as breath (CO2)-C-13. In this study, we used a b reath-by-breath analysis of (CO2)-C-13 to depict the washout of (CO2)-C-13 at a high temporal resolution to analyze the extent to which a probable fir st-pass effect is responsible for the reduced recovery. Eight healthy men w ere tested at seated rest and with bicycle exercise at a constant load rela tive to 40 and 75% maximal O-2 consumption ((V) over dot O-2 max). [C-13]bi carbonate (0.0125 g/kg body wt) was administered as an intravenous bolus in each test. Respiratory mass spectrometry was used to derive the course of the end-tidal (CO2)-C-13- to-(CO2)-C-12 ratio from the breath-by-breath dat a. Approximately 2 min after C-13 administration, the washout curve could b e fitted well by a two-exponential curve describing a two-compartment mammi llary model. Immediately after administration of the bolus dose, an excess peak in the end-tidal (CO2)-C-13- to-(CO2)-C-12 ratio appeared. This peak c ould not be included in the two-exponential fitting. The area under the fir st peak resulted in 3.8 +/- 1.3% of the total [C-13]bicarbonate dose at res t, 11.5 +/- 2.9% at moderate exercise (40% (V) over dot O-2 max), and 16.9 +/- 4.0% at intensive exercise (75% (V) over dot O-2 max). The first-pass e ffect had an increasing impact of up to about two-thirds of the lacking bic arbonate with higher exercise intensity. The "loss" of tracer via this firs t-pass effect must be considered when the results of studies with parentera l administration of [C-13]bicarbonate are considered, especially when it is given as a bolus dose and during exercise.