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

The dilution of an intravenous bolus dose of [13C]bicarbonate is used as an estimate for the metabolic rate under certain conditions. It is a consistent finding in all studies that the total amount of intravenous [13C]bicarbonate cannot be recovered as breath 13CO2. In this study, we used a breath-by-breath analysis of 13CO2 to depict the washout of 13CO2 at a high temporal resolution to analyze the extent to which a probable first-pass effect is responsible for the reduced recovery. Eight healthy men were tested at seated rest and with bicycle exercise at a constant load relative to 40 and 75% maximal O2 consumption VO2 max). [13C]bicarbonate (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 13CO2-to-12CO2 ratio from the breath-by-breath data. Approximately 2 min after 13C administration, the washout curve could be fitted well by a two-exponential curve describing a two-compartment mammillary model. Immediately after administration of the bolus dose, an excess peak in the end-tidal 13CO2-to-12CO2 ratio appeared. This peak could not be included in the two-exponential fitting. The area under the first peak resulted in 3.8 +/- 1.3% of the total [13C]bicarbonate dose at rest, 11.5 +/- 2.9% at moderate exercise (40% VO2 max), and 16.9 +/- 4.0% at intensive exercise (75% VO2 max). The first-pass effect had an increasing impact of up to about two-thirds of the lacking bicarbonate with higher exercise intensity. The "loss" of tracer via this first-pass effect must be considered when the results of studies with parenteral administration of [13C]bicarbonate are considered, especially when it is given as a bolus dose and during exercise.