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.
Roecker
K
K
Department of Sports Medicine, Medical Clinic and Polyclinic, University of Tuebingen, D-72074 Tuebingen, Germany. kai.roecker@uni-tuebingen.de
Landaw
E
E
Striegel
H
H
Mayer
F
F
Dickhuth
H H
HH
D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D001639:Bicarbonates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D005080:Exercise Test; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008176:Lung Volume Measurements; D008297:Male; D011659:Pulmonary Gas Exchange / Q000502:physiology; D015656:Respiratory Mechanics / Q000187:drug effects*
D001639:Bicarbonates; D002250:Carbon Radioisotopes