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

Abstract

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.

The oral13C-bicarbonate technique for estimation of energy expenditure in dogs: validation against indirect calorimetry

“…Larsson et al compared to measurements during resting conditions Elia et al 1992;Roecker et al 2001). Larsson et al compared to measurements during resting conditions Elia et al 1992;Roecker et al 2001).…”

Gas Exchange Measurements with High Temporal Resolution: The Breath-by-Breath Approach

“…It has the option to determine more gases than O 2 and CO 2 in a sufficient temporal resolution. Examples are stable isotopes [44], inert gases [41], or even nitrogen [25]. Notably, mass spectrometers are measuring true fractional gas concentrations and not partial pressures like conventional systems.…”

“…For example, BBB estimations of gas exchange kinetics may be applied to other gases than O 2 and CO 2 . Using respiratory mass spectrometry or similar sensors, breath-wise kinetics of nitrogen breathing [20,31] or stable isotopes [43,44] may have potential. Combinations of the BBB approach with mixing chambers to detect traces of expired nitric oxide by chemiluminescence have been performed in clinical applications a few years ago [1].…”

Interpretation of non-invasive breath tests using 13C-labeled substrates - a preliminary report with 13C-methacetin

“…It is known that emerging bicarbonate has a relatively long halftime of approx. 60 minutes [14] and that ultimately only 70% of the emerging 13 CO 2 is excreted [15]. This could significantly interfere with NBT results [8].…”